Rheumatoid Arthritis
Conditions
Brief summary
This is a multicenter observational study in patients with rheumatoid arthritis in routine clinical practice in Italy. In the retrospective Part 1 of the study, clinical and demographic factors associated with the use of a biologic drug in monotherapy as compared to therapy in combination with Disease-modifying anti-rheumatic drugs (DMARDs) will be evaluated. In the retrospective/prospective Part 2 of the study, efficacy and safety of the use of RoActemra/Actemra (tocilizumab) in monotherapy will be evaluated. Patients will be followed for up to18 months.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1: * Adult patients, \>/= 18 years of age * Diagnosis of rheumatoid arthritis according to American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria * Patients who received at least one cycle of biologic therapy, either in monotherapy or in combination, in the 12 months preceding the opening of the first site Part 2: * Patients on monotherapy with RoActemra/Actemra already enrolled in Part 1 of the study
Exclusion criteria
* Patients simultaneously participating in other studies with RoActemra/Actemra at the time of signing informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Demographic characteristics were analyzed in participants at Baseline, where Baseline is considered as the study entry visit (day of informed consent form signed). Demographic characteristics which were taken into account included age in years, race, height in centimeters (cm), weight in Kilograms (Kg), and Body Mass Index (BMI) in Kg/cm\^2. Participants with age =\<, \> 59 years, height =\<, \> 163 cm, weight =\<, \> 65.85 Kg and BMI =\<, \> 24.98 Kg/cm\^2 are reported. |
| Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The duration of disease is defined as the total time from the diagnosis of rheumatoid arthritis (RA) until the study entry. |
| Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Comorbidity is the presence of previous or concomitant diseases. |
| Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The autoantibody included seropositive or seronegative participants for rheumatoid factor (RF) and/or anti-cyclic citrullinated protein antibodies (Anti-CCP). RF value higher than 20 Units (U)/milliliter (mL) is considered seropositive and anti-CCP antibodies value higher than 10 U/mL is considered positive. |
| Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The Health Assessment Questionnaire- Disability Index (HAQ-DI) is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days. Participants with scores =\< 0.8625 and \> 0.8625 are reported. |
| Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The disease activity included Disease Activity Score 28 (DAS28). The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen joint counts (SJC) and tender joint counts (TJC), acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity; where higher scores represents higher disease activity. The DAS =\< 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity. Participants with DAS28 score =\< 2.6 and \> 2.6 are reported. |
| Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The disease activity included biological markers of inflammation: C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). A reduction in CRP and ESR values indicates improvement. Participants with CRP values =\< 0.28 and \>2.8 milligram/deciliter (mg/dL); and ESR values =\< 11 and \>11 millimeters/hour (mm/hr) are reported. |
| Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The disease activity included Clinical Disease Activity Index (CDAI) which is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and patient's global assessment (PtGA) and physician's global assessment (PhGA) assessed on 0-10 cm visual analog scale (VAS), where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity. Participants with CDAI score =\< 7.75 and \> 7.75 are reported. |
| Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The disease activity included Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. Participants with SDAI score =\< 8.17 and \> 8.17 are reported. |
| Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The duration of combination therapy before monotherapy are reported. The duration was estimated by calculating total duration from starting the combination therapy till the participant switched to monotherapy. Participants who started the combination therapy and later switched to monotherapy =\< 337 days, \> 337 days, =\< 336 days, \> 336 days are reported. |
| Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy | At Baseline (Day of informed consent form signed) | The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs and the second treatment line as the subsequent use of a different biologic drug. Participants who adopted monotherapy as =\< 2 and \> 2 therapy lines are reported. According to the study protocol objectives, this analysis was performed only for Monotherapy arm. |
| Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Participants who received at least one previous treatment with biologics in monotherapy and no previous monotherapy with biologics are reported. |
| Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Participants who had prevalence with at least one previous switch, swaps, and switch/swap to other therapy are reported. |
| Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | At Baseline (Day of informed consent form signed) | Reasons leading to the use of biologic in monotherapy includes DMARDs intolerance, insufficient therapeutic effect, intolerance to biologic drug, low participant's compliance, concomitant pathologies, pregnancy desire, remission from combination therapy, remission from monotherapy, others and unknown. Participants with reason leading to the use of biologic in monotherapy are presented. According to the study protocol objectives, this analysis was performed only for Monotherapy arm. |
| Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Up to 18 months | The probabilities of participant to retain on therapy at various time points are reported. |
| Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18 | At month 18 | Participants who retained the therapy were analyzed for disease activity (DAS28 ESR) at Month 18. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | Participants who maintained delta DAS28 ESR of \>= 0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); where decrease in score indicated improvement of disease. |
| Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC (28 joints) + 0.28 square root of SJC (28 joints) + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 CRP \< 2.6 indicates disease remission and \>=2.6 to 3.2 indicates low disease activity. |
| Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 ESR \< 2.6 indicates disease remission and \>=2.6 to 3.2 indicates low disease activity. |
| Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | Percentage of participants achieving CDAI remission \< 2.8, after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. CDAI is the numerical sum of four outcome parameters: TJC, SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity. |
| Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | Percentage of participant achieving SDAI remission (\< 3.3), after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy is reported. The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA which (based on 0-10 cm VAS, 0 = no disease activity and 10 = worst disease activity, where higher scores represent higher disease activity), and CRP. The SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity. |
| Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | The mean change from Baseline (day of the first infusion with tocilizumab as monotherapy) in the TJC And SJC after 3, 6, 12 and 18 months is reported. The TJC and SJC were determined for 28 joint counts. The scores ranged from 0 (no disease activity) to 28 (higher/worsen disease activity), where higher scores represents higher disease activity. |
| Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Mean Change From Baseline (day of the first infusion with tocilizumab as monotherapy) in the dose of corticosteroids after 3, 6, 12 and 18 months from Baseline is reported. |
| Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Mean change from baseline in aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase levels are reported. |
| Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | Percentage of participants with change in HAQ (Delta HAQ) of \>= 0.21 after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. The HAQ consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. |
| Phase II: Mean VAS Fatigue Score Overtime | At Baseline (Day of first administration of TCZ as a monotherapy) and Months 3, 6, 12, and 18 | The VAS fatigue score ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity). Higher score indicate worsening. |
| Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events | Up to 18 months | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AE. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect. The AE were captured only for Phase II. |
| Phase II: Number of Participants With Retention in Therapy Without Interruption Due to Side Effects | Up to 18 months | Number of participants who retained in therapy without interruption due to side effects is reported. |
| Phase II: Number of Side Effects That Had Not Induced Discontinuation of Treatment | Up to 18 months | Number of side effects (AEs) that had not induced discontinuation of treatment is reported. The AEs were captured only for Phase II. |
| Phase II: Number of Side Effects That Induced Transient Interruption of Treatment | Up to 18 months | Number of side effects (AEs) that induced transient interruption of treatment is reported. The AEs were captured only for Phase II. |
| Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | The mean change in hemoglobin concentration was calculated by subtracting the baseline hemoglobin concentration from the monthly hemoglobin concentration is reported. |
| Phase I: Median Disease Duration in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The duration of disease is defined as the total time from the diagnosis of RA until the study entry. |
| Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Mean change from baseline in red blood cells (RBC), white blood cells (WBC) and platelets are reported. |
| Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Mean change from baseline in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), total bilirubin, direct bilirubin, glucose, creatinine, blood urea nitrogen (BUN) levels are reported. |
| Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Serum electrophoresis parameters includes albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, gamma globulin was reported. Mean change from Baseline values are reported at each time points. |
| Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18 | Mean Change from Baseline in hematocrit, neutrophils, eosinophils, basophils, lymphocytes, monocytes are reported. |
| Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Comorbidity is the presence of previous or concomitant diseases. Percentage of participants with comorbidity is reported. |
| Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The HAQ-DI is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days. |
| Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy | At Baseline (Day of informed consent form signed) | The table below shows percentage participants who started treatment with a biologic drug in monotherapy compared with percentage of participants who stopped DMARDs while taking a biologic drug in combination. |
| Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | At Baseline (Day of informed consent form signed) | The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs, the second treatment line as the subsequent use of a different biologic drug and so on for the third, fourth, fifth and sixth treatment line. According to the study protocol objectives, this analysis was performed only for Monotherapy arm. |
| Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Number of participants who received at least one previous treatment with a biologic drug as a monotherapy in both groups is reported. |
| Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Participants who had prevalence with at least one previous switch, swaps or switch/swap to other therapy either monotherapy or combination therapy are reported. |
| Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity) where higher scores represents higher disease. The DAS28 \<2.6 indicates disease remission, \>=2.6 and \<3.2 indicates Low disease activity, \>=3.2 and \<=5.1 indicates Moderate disease activity and \>5.1 indicates High disease activity. Median score for DAS28 at the study entry (Baseline) is reported. |
| Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity. Number of participants with CDAI scores for both the groups at study entry (baseline) are reported. |
| Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (assessed on 0-10 cm) VAS; 0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. |
| Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Mean of tender and swollen joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender and swollen joints was recorded on the joint assessment as no tenderness = 0 and tenderness = 1. |
| Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | The percentage of participants treated with corticosteroids at enrollment is reported. |
| Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Mean dose of corticosteroids at study entry (Baseline) is reported. |
| Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy | At Baseline (Day of informed consent form signed) | Mean duration of previous treatment with a biologic drug in monotherapy are reported. |
| Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy | At Baseline (Day of informed consent form signed) | Mean duration of treatment with a biologic drug in combination with DMARDs before monotherapy is reported in days. |
| Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 | At Months 3, 6, 12, and 18 | Participants who maintained the change in DAS28 (Delta DAS28) CRP of \>=0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC 28 + 0.28 square root of SJC 28 + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP- scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. |
Countries
Italy
Participant flow
Recruitment details
A total of 304 participants were enrolled in the study conducted from May 2013 to October 2014 at 29 centers in Italy.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy Eligible participants who received any biologic drug as a monotherapy in the 12 months prior to the study entry were observed for Phase I. Participants who were enrolled in Phase I and received TCZ as a monotherapy were observed for 18 months from the first infusion of TCZ in Phase II, where TCZ was prescribed according to the approved product information, local treatment guidelines and/or routine clinical practice. | 152 |
| Combination Therapy Eligible participants who received any biologic drug in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the 12 months prior to study entry were observed for Phase I. | 152 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase II | Adverse Event | 2 | 0 |
| Phase II | Lack of Efficacy | 6 | 0 |
| Phase II | Lost to Follow-up | 1 | 0 |
| Phase II | Physician's decision | 1 | 0 |
| Phase II | Remission of disease | 1 | 0 |
| Phase II | Safety | 1 | 0 |
Baseline characteristics
| Characteristic | Monotherapy | Combination Therapy | Total |
|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 12.5 | 59.4 years STANDARD_DEVIATION 10.9 | 58.4 years STANDARD_DEVIATION 11.8 |
| Gender Female | 130 Participants | 127 Participants | 257 Participants |
| Gender Male | 22 Participants | 25 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 104 |
| serious Total, serious adverse events | 5 / 104 |
Outcome results
Primary
Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy
The probabilities of participant to retain on therapy at various time points are reported.
Time frame: Up to 18 months
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 323 | 93.3 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 375 | 92.3 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 1 | 99.0 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 33 | 97.1 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 66 | 96.2 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 168 | 95.2 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 236 | 94.2 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 414 | 91.3 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 423 | 90.4 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 442 | 89.4 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Who Retained on Tocilizumab Monotherapy | Day 459 | 88.5 Percentage of participants |
Primary
Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18
Participants who retained the therapy were analyzed for disease activity (DAS28 ESR) at Month 18. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.
Time frame: At month 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18 | DAS28 ESR<2.6 | 64.71 Percentage of participants |
| Monotherapy | Phase II: Retention Rate in Therapy, Percentage of Participants Achieving DAS 28 ESR <2.6 and <3.2 at Month 18 | DAS 28 ESR > 2.6 to =<3.2 | 80.39 Percentage of participants |
Comparison: The relation between retention rate and DAS28 (\<2.6 vs \<3.2) was assayed with the Cox regression.p-value: 0.119495% CI: [0.65, 19.33]Regression, Cox
Primary
Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy
Participants who received at least one previous treatment with biologics in monotherapy and no previous monotherapy with biologics are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy | No biologics | 95 Participants |
| Monotherapy | Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy | At least one biologics | 57 Participants |
| Combination Therapy | Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy | No biologics | 125 Participants |
| Combination Therapy | Phase I: Number of Biologics Administered as Monotherapy in Monotherapy and Combination Therapy | At least one biologics | 27 Participants |
Primary
Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy
The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs and the second treatment line as the subsequent use of a different biologic drug. Participants who adopted monotherapy as =\< 2 and \> 2 therapy lines are reported. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy | Treatment line, =< 2 | 106 Participants |
| Monotherapy | Phase I: Number of Participants Treatment Line in Which Monotherapy Has Been Adopted in Monotherapy | Treatment line, > 2 | 46 Participants |
Primary
Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy
The autoantibody included seropositive or seronegative participants for rheumatoid factor (RF) and/or anti-cyclic citrullinated protein antibodies (Anti-CCP). RF value higher than 20 Units (U)/milliliter (mL) is considered seropositive and anti-CCP antibodies value higher than 10 U/mL is considered positive.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | RF Positive (n= 128, 128) | 69 Participants |
| Monotherapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | RF Negative (n= 128, 128) | 59 Participants |
| Monotherapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | Anti-CCP Positive (n= 100, 103) | 61 Participants |
| Monotherapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | Anti-CCP Negative (n= 100, 103) | 39 Participants |
| Combination Therapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | Anti-CCP Negative (n= 100, 103) | 31 Participants |
| Combination Therapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | RF Positive (n= 128, 128) | 79 Participants |
| Combination Therapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | Anti-CCP Positive (n= 100, 103) | 72 Participants |
| Combination Therapy | Phase I: Number of Participants With Autoantibody Status (Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies) in Monotherapy and Combination Therapy | RF Negative (n= 128, 128) | 49 Participants |
Primary
Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy
The disease activity included Clinical Disease Activity Index (CDAI) which is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and patient's global assessment (PtGA) and physician's global assessment (PhGA) assessed on 0-10 cm visual analog scale (VAS), where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity. Participants with CDAI score =\< 7.75 and \> 7.75 are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at Baseline are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy | CDAI Score =< 7.75 | 37 Participants |
| Monotherapy | Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy | CDAI Score > 7.75 | 37 Participants |
| Combination Therapy | Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy | CDAI Score =< 7.75 | 39 Participants |
| Combination Therapy | Phase I: Number of Participants With Clinical Disease Activity Index in Monotherapy and Combination Therapy | CDAI Score > 7.75 | 38 Participants |
Primary
Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy
Comorbidity is the presence of previous or concomitant diseases.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy | 121 Participants |
| Combination Therapy | Phase I: Number of Participants With Comorbidity in Monotherapy and Combination Therapy | 116 Participants |
Primary
Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy
The disease activity included biological markers of inflammation: C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). A reduction in CRP and ESR values indicates improvement. Participants with CRP values =\< 0.28 and \>2.8 milligram/deciliter (mg/dL); and ESR values =\< 11 and \>11 millimeters/hour (mm/hr) are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at Baseline are reported. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | CRP =< 0.28 mg/dL (n= 128, 129) | 66 Participants |
| Monotherapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | CRP > 0.28 mg/dL (n= 128, 129) | 62 Participants |
| Monotherapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | ESR =< 11 mm/h (n= 135, 136) | 80 Participants |
| Monotherapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | ESR > 11 mm/h (n= 135, 136) | 55 Participants |
| Combination Therapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | ESR > 11 mm/h (n= 135, 136) | 77 Participants |
| Combination Therapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | ESR =< 11 mm/h (n= 135, 136) | 59 Participants |
| Combination Therapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | CRP > 0.28 mg/dL (n= 128, 129) | 65 Participants |
| Combination Therapy | Phase I: Number of Participants With C-Reactive Protein Value and Erythrocyte Sedimentation Rate in Monotherapy and Combination Therapy | CRP =< 0.28 mg/dL (n= 128, 129) | 64 Participants |
Primary
Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy
Demographic characteristics were analyzed in participants at Baseline, where Baseline is considered as the study entry visit (day of informed consent form signed). Demographic characteristics which were taken into account included age in years, race, height in centimeters (cm), weight in Kilograms (Kg), and Body Mass Index (BMI) in Kg/cm\^2. Participants with age =\<, \> 59 years, height =\<, \> 163 cm, weight =\<, \> 65.85 Kg and BMI =\<, \> 24.98 Kg/cm\^2 are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Height >163 cm (n= 149, 150) | 68 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Race Caucasian (n= 152, 152) | 152 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Weight =< 65.85 Kg (n= 152, 152) | 84 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Age > 59 years (n= 152, 152) | 73 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Weight > 65.85 Kg, (n= 152, 152) | 68 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | BMI =< 24.98 Kg/cm^2 (n= 149, 150) | 77 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Height =< 163 cm (n= 149, 150) | 81 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | BMI > 24.98 Kg/cm^2 (n= 149, 150) | 72 Participants |
| Monotherapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Age =< 59 years (n= 152, 152) | 79 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | BMI > 24.98 Kg/cm^2 (n= 149, 150) | 76 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Age =< 59 years (n= 152, 152) | 75 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Age > 59 years (n= 152, 152) | 77 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Race Caucasian (n= 152, 152) | 150 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Height =< 163 cm (n= 149, 150) | 69 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Height >163 cm (n= 149, 150) | 81 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Weight =< 65.85 Kg (n= 152, 152) | 68 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | BMI =< 24.98 Kg/cm^2 (n= 149, 150) | 74 Participants |
| Combination Therapy | Phase I: Number of Participants With Demographic Characteristics in Monotherapy and Combination Therapy | Weight > 65.85 Kg, (n= 152, 152) | 84 Participants |
Primary
Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy
The disease activity included Disease Activity Score 28 (DAS28). The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen joint counts (SJC) and tender joint counts (TJC), acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity; where higher scores represents higher disease activity. The DAS =\< 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity. Participants with DAS28 score =\< 2.6 and \> 2.6 are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at Baseline are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy | DAS28 with =< 2.6 score | 67 Participants |
| Monotherapy | Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy | DAS28 with >2.6 score | 54 Participants |
| Combination Therapy | Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy | DAS28 with =< 2.6 score | 55 Participants |
| Combination Therapy | Phase I: Number of Participants With Disease Activity Score 28 in Monotherapy and Combination Therapy | DAS28 with >2.6 score | 67 Participants |
Primary
Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy
The duration of disease is defined as the total time from the diagnosis of rheumatoid arthritis (RA) until the study entry.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy | Duration of disease =< 124 months | 74 Participants |
| Monotherapy | Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy | Duration of disease > 124 months | 78 Participants |
| Combination Therapy | Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy | Duration of disease =< 124 months | 81 Participants |
| Combination Therapy | Phase I: Number of Participants With Disease Duration in Monotherapy and Combination Therapy | Duration of disease > 124 months | 71 Participants |
Primary
Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy
The duration of combination therapy before monotherapy are reported. The duration was estimated by calculating total duration from starting the combination therapy till the participant switched to monotherapy. Participants who started the combination therapy and later switched to monotherapy =\< 337 days, \> 337 days, =\< 336 days, \> 336 days are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 1, =< 337 (n= 81, 74) | 45 Participants |
| Monotherapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 2, =< 336 (n= 64, 60) | 36 Participants |
| Monotherapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 1, > 337 (n= 81, 74) | 36 Participants |
| Monotherapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 2, > 336 (n= 64, 60 ) | 28 Participants |
| Combination Therapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 1, > 337 (n= 81, 74) | 41 Participants |
| Combination Therapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 1, =< 337 (n= 81, 74) | 33 Participants |
| Combination Therapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 2, > 336 (n= 64, 60 ) | 34 Participants |
| Combination Therapy | Phase I: Number of Participants With Duration of Combination Therapy Before Monotherapy in Monotherapy and Combination Therapy | Duration of combination type 2, =< 336 (n= 64, 60) | 26 Participants |
Primary
Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy
The Health Assessment Questionnaire- Disability Index (HAQ-DI) is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days. Participants with scores =\< 0.8625 and \> 0.8625 are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at the time of evaluation are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy | HAQ-DI Score =< 0.8625 | 42 Participants |
| Monotherapy | Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy | HAQ-DI Score >0.8625 | 42 Participants |
| Combination Therapy | Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy | HAQ-DI Score =< 0.8625 | 40 Participants |
| Combination Therapy | Phase I: Number of Participants With Health Assessment Questionnaire- Disability Index in Monotherapy and Combination Therapy | HAQ-DI Score >0.8625 | 40 Participants |
Primary
Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy
Participants who had prevalence with at least one previous switch, swaps, and switch/swap to other therapy are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one switch | 30 Participants |
| Monotherapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one swap | 74 Participants |
| Monotherapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one switch/swap | 81 Participants |
| Combination Therapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one swap | 56 Participants |
| Combination Therapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one switch | 40 Participants |
| Combination Therapy | Phase I: Number of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | At least one switch/swap | 75 Participants |
Primary
Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy
Reasons leading to the use of biologic in monotherapy includes DMARDs intolerance, insufficient therapeutic effect, intolerance to biologic drug, low participant's compliance, concomitant pathologies, pregnancy desire, remission from combination therapy, remission from monotherapy, others and unknown. Participants with reason leading to the use of biologic in monotherapy are presented. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | DMARDs intolerance | 41 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Insufficient therapeutic effect | 68 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Intolerance to biologic drug | 7 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Low participant compliance | 5 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Concomitant pathologies | 4 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Pregnancy desire | 3 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Remission from combination therapy | 9 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Remission from monotherapy | 3 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Others | 8 Participants |
| Monotherapy | Phase I: Number of Participants With Reasons Leading to the Use of Biologic in Monotherapy | Unknown | 3 Participants |
Primary
Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy
The disease activity included Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity. Participants with SDAI score =\< 8.17 and \> 8.17 are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available data at Baseline are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy | SDAI Score =< 8.17 | 36 Participants |
| Monotherapy | Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy | SDAI Score > 8.17 | 36 Participants |
| Combination Therapy | Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy | SDAI Score =< 8.17 | 35 Participants |
| Combination Therapy | Phase I: Number of Participants With Simplified Disease Activity Index in Monotherapy and Combination Therapy | SDAI Score > 8.17 | 34 Participants |
Secondary
Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time
Mean change from baseline in aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase levels are reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | AST, Month 3 (n= 74) | 0.75 Units/Liter | Standard Deviation 9.35 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | AST, Month 6 (n= 74) | 0.87 Units/Liter | Standard Deviation 9.39 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | AST, Month 12 (n= 74) | 0.78 Units/Liter | Standard Deviation 8.47 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | AST, Month 18 (n= 68) | 1.53 Units/Liter | Standard Deviation 13.4 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | ALT, Month 3 (n= 74) | 3.08 Units/Liter | Standard Deviation 20.65 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | ALT, Month 6 (n= 76) | 0.60 Units/Liter | Standard Deviation 20.49 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | ALT, Month 12 (n= 76) | 0.08 Units/Liter | Standard Deviation 16.15 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | ALT, Month 18 (n= 68) | 0.22 Units/Liter | Standard Deviation 18.27 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | GGT, Month 3 (n= 25) | -0.84 Units/Liter | Standard Deviation 20.45 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | GGT, Month 6 (n= 32) | -6.19 Units/Liter | Standard Deviation 24.68 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | GGT, Month 12 (n= 30) | -4.60 Units/Liter | Standard Deviation 21.5 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | GGT, Month 18 (n= 25) | -7.48 Units/Liter | Standard Deviation 26.5 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | Alkaline phosphatase, Month 3 (n= 20) | -15.10 Units/Liter | Standard Deviation 38.22 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | Alkaline phosphatase, Month 6 (n= 21) | -21.86 Units/Liter | Standard Deviation 38.02 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | Alkaline phosphatase, Month 12 (n= 24) | -18.17 Units/Liter | Standard Deviation 44.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyl Transpeptidase, and Alkaline Phosphatase Levels Over Time | Alkaline phosphatase, Month 18 (n= 15) | -21.60 Units/Liter | Standard Deviation 53.45 |
Secondary
Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18
Mean Change From Baseline (day of the first infusion with tocilizumab as monotherapy) in the dose of corticosteroids after 3, 6, 12 and 18 months from Baseline is reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 | Month 3 (n= 60) | -0.85 milligrams | Standard Deviation 4.18 |
| Monotherapy | Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 | Month 6 (n= 54) | -1.24 milligrams | Standard Deviation 2.28 |
| Monotherapy | Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 | Month 12 (n= 41) | -1.71 milligrams | Standard Deviation 2.76 |
| Monotherapy | Phase II: Mean Change From Baseline in Dose of Corticosteroids at Months 3, 6, 12, and 18 | Month 18 (n= 38) | -1.08 milligrams | Standard Deviation 2.12 |
Secondary
Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time
Mean Change from Baseline in hematocrit, neutrophils, eosinophils, basophils, lymphocytes, monocytes are reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Hematocrit, Month 3 (n= 60) | 5.73 Percentage of cells | Standard Deviation 36.25 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Hematocrit, Month 6 (n= 57) | -0.11 Percentage of cells | Standard Deviation 7.12 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Hematocrit, Month 12 (n= 57) | 0.32 Percentage of cells | Standard Deviation 7.26 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Hematocrit, Month 18 (n= 53) | -0.35 Percentage of cells | Standard Deviation 8.35 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Neutrophils, Month 3 (n= 61) | -7.82 Percentage of cells | Standard Deviation 11.96 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Neutrophils, Month 6 (n= 64) | -7.69 Percentage of cells | Standard Deviation 11.35 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Neutrophils, Month 12 (n= 57) | -7.16 Percentage of cells | Standard Deviation 11.99 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Neutrophils, Month 18 (n= 55) | -6.69 Percentage of cells | Standard Deviation 13.32 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Eosinophils, Month 3 (n= 58) | 1.21 Percentage of cells | Standard Deviation 2.54 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Eosinophils, Month 6 (n= 59) | 1.25 Percentage of cells | Standard Deviation 2.11 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Eosinophils, Month 12 (n= 52) | 1.30 Percentage of cells | Standard Deviation 2.49 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Eosinophils, Month 18 (n= 51) | 1.31 Percentage of cells | Standard Deviation 2.16 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Basophils, Month 3 (n= 58) | 0.14 Percentage of cells | Standard Deviation 0.67 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Basophils, Month 6 (n= 59) | 0.26 Percentage of cells | Standard Deviation 0.63 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Basophils, Month 12 (n= 52) | 0.19 Percentage of cells | Standard Deviation 0.47 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Basophils, Month 18 (n= 51) | 0.18 Percentage of cells | Standard Deviation 0.41 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Lymphocytes, Month 3 (n= 60) | 5.58 Percentage of cells | Standard Deviation 9.05 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Lymphocytes, Month 6 (n= 64) | 5.60 Percentage of cells | Standard Deviation 9.5 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Lymphocytes, Month 12 (n= 57) | 4.98 Percentage of cells | Standard Deviation 9.67 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Lymphocytes, Month 18 (n= 55) | 4.55 Percentage of cells | Standard Deviation 11.45 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Monocytes, Month 3 (n= 58) | 0.61 Percentage of cells | Standard Deviation 2.87 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Monocytes, Month 6 (n= 59) | 1.13 Percentage of cells | Standard Deviation 2.75 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Monocytes, Month 12 (n= 52) | 0.46 Percentage of cells | Standard Deviation 2.38 |
| Monotherapy | Phase II: Mean Change From Baseline in Hematocrit, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes Over Time | Monocytes, Month 18 (n= 51) | 0.59 Percentage of cells | Standard Deviation 2.74 |
Secondary
Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time
The mean change in hemoglobin concentration was calculated by subtracting the baseline hemoglobin concentration from the monthly hemoglobin concentration is reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time | Month 3 (n= 83) | 0.41 gram/dL | Standard Deviation 0.84 |
| Monotherapy | Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time | Month 6 (n= 84) | 0.34 gram/dL | Standard Deviation 0.91 |
| Monotherapy | Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time | Month 12 (n= 80) | 0.44 gram/dL | Standard Deviation 1.01 |
| Monotherapy | Phase II: Mean Change From Baseline in Hemoglobin Levels Over Time | Month 18 (n= 76) | 0.49 gram/dL | Standard Deviation 1.16 |
Secondary
Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time
Mean change from baseline in red blood cells (RBC), white blood cells (WBC) and platelets are reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | Platelets, Month 6 (n= 75) | -62.12 10^6 cells/microliter | Standard Deviation 72.58 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | RBC, Month 3 (n= 71) | 0.07 10^6 cells/microliter | Standard Deviation 0.32 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | RBC, Month 6 (n= 70) | -0.01 10^6 cells/microliter | Standard Deviation 0.3 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | RBC, Month 12 (n= 69) | 0.04 10^6 cells/microliter | Standard Deviation 0.32 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | RBC, Month 18 (n= 63) | 0.05 10^6 cells/microliter | Standard Deviation 0.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | WBC, Month 3 (n= 83) | -1.14 10^6 cells/microliter | Standard Deviation 2.01 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | WBC, Month 6 (n= 84) | -1.30 10^6 cells/microliter | Standard Deviation 2.27 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | WBC, Month 12 (n= 81) | -1.30 10^6 cells/microliter | Standard Deviation 2.09 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | WBC, Month 18 (n= 75) | -1.48 10^6 cells/microliter | Standard Deviation 2.15 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | Platelets, Month 3 (n= 78) | -52.38 10^6 cells/microliter | Standard Deviation 71.21 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | Platelets, Month 12 (n= 73) | -54.42 10^6 cells/microliter | Standard Deviation 73.4 |
| Monotherapy | Phase II: Mean Change From Baseline in Red Blood Cells, White Blood Cells, and Platelets Over Time | Platelets, Month 18 (n= 72) | -57.88 10^6 cells/microliter | Standard Deviation 76.15 |
Secondary
Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time
Serum electrophoresis parameters includes albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, gamma globulin was reported. Mean change from Baseline values are reported at each time points.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Albumin, Month 3 (n= 25) | 3.92 Percentage of concentration | Standard Deviation 4.23 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Albumin, Month 6 (n= 25) | 5.23 Percentage of concentration | Standard Deviation 3.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Albumin, Month 12 (n= 24) | 5.35 Percentage of concentration | Standard Deviation 5.14 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Albumin, Month 18 (n= 19) | 5.95 Percentage of concentration | Standard Deviation 4.45 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-1 globulin, Month 3 (n= 26) | -0.85 Percentage of concentration | Standard Deviation 0.94 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-1 globulin, Month 6 (n= 25) | -1.09 Percentage of concentration | Standard Deviation 0.91 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-1 globulin, Month 12 (n= 25) | -1.00 Percentage of concentration | Standard Deviation 1.1 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-1 globulin, Month 18 (n= 19) | -1.11 Percentage of concentration | Standard Deviation 1.03 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-2 globulin, Month 3 (n= 25) | -1.74 Percentage of concentration | Standard Deviation 2.12 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-2 globulin, Month 6 (n= 25) | -1.68 Percentage of concentration | Standard Deviation 2.3 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-2 globulin, Month 12 (n= 24) | -1.91 Percentage of concentration | Standard Deviation 1.95 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Alpha-2 globulin, Month 18 (n= 19) | -2.34 Percentage of concentration | Standard Deviation 1.89 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Beta globulin, Month 3 (n= 25) | -0.94 Percentage of concentration | Standard Deviation 1.36 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Beta globulin, Month 6 (n= 24) | -1.19 Percentage of concentration | Standard Deviation 1.43 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Beta globulin, Month 12 (n= 24) | -0.91 Percentage of concentration | Standard Deviation 1.41 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Beta globulin, Month 18 (n= 19) | -1.07 Percentage of concentration | Standard Deviation 1.18 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Gamma globulin, Month 3 (n= 25) | -0.51 Percentage of concentration | Standard Deviation 1.96 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Gamma globulin, Month 6 (n= 26) | -1.75 Percentage of concentration | Standard Deviation 3.46 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Gamma globulin, Month 12 (n= 24) | -1.51 Percentage of concentration | Standard Deviation 2.44 |
| Monotherapy | Phase II: Mean Change From Baseline in Serum Electrophoresis Parameters Over Time | Gamma globulin, Month 18 (n= 19) | -1.52 Percentage of concentration | Standard Deviation 2.62 |
Secondary
Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18
The mean change from Baseline (day of the first infusion with tocilizumab as monotherapy) in the TJC And SJC after 3, 6, 12 and 18 months is reported. The TJC and SJC were determined for 28 joint counts. The scores ranged from 0 (no disease activity) to 28 (higher/worsen disease activity), where higher scores represents higher disease activity.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | TJC, Month 6 (n= 80) | -4.13 Joints | Standard Deviation 5.51 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | TJC, Month 12 (n= 72) | -4.33 Joints | Standard Deviation 6.14 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | SJC, Month 18 (n= 69) | -2.46 Joints | Standard Deviation 3.75 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | SJC, Month 12 (n= 72) | -2.21 Joints | Standard Deviation 3.76 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | TJC, Month 3 (n= 78) | -2.74 Joints | Standard Deviation 6.87 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | TJC, Month 18 (n= 69) | -4.30 Joints | Standard Deviation 5.89 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | SJC, Month 3 (n= 78) | -1.65 Joints | Standard Deviation 3.98 |
| Monotherapy | Phase II: Mean Change From Baseline in TJC And SJC at Months 3, 6, 12, and 18 | SJC, Month 6 (n= 80) | -2.39 Joints | Standard Deviation 3.47 |
Secondary
Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time
Mean change from baseline in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), total bilirubin, direct bilirubin, glucose, creatinine, blood urea nitrogen (BUN) levels are reported.
Time frame: From Baseline (Day of first administration of TCZ as a monotherapy) to Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Cholesterol, Month 3 (n= 27) | 10.04 mg/dL | Standard Deviation 42.31 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Cholesterol, Month 6 (n= 28) | 12.61 mg/dL | Standard Deviation 49.76 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Cholesterol, Month 12 (n= 31) | 4.81 mg/dL | Standard Deviation 41.59 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Cholesterol, Month 18 (n= 28) | 5.57 mg/dL | Standard Deviation 49 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | LDL Cholesterol, Month 3 (n= 14) | -3.63 mg/dL | Standard Deviation 24.89 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | LDL Cholesterol, Month 6 (n= 14) | 13.93 mg/dL | Standard Deviation 38.99 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | LDL Cholesterol, Month 12 (n= 16) | -2.59 mg/dL | Standard Deviation 37.1 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | LDL Cholesterol, Month 18 (n= 14) | 3.53 mg/dL | Standard Deviation 38.31 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | HDL Cholesterol, Month 3 (n= 19) | 4.16 mg/dL | Standard Deviation 6.34 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | HDL Cholesterol, Month 6 (n= 18) | 0.67 mg/dL | Standard Deviation 11.42 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | HDL Cholesterol, Month 12 (n= 19) | -1.74 mg/dL | Standard Deviation 12.61 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | HDL Cholesterol, Month 18 (n= 18) | -1.67 mg/dL | Standard Deviation 15.46 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | TG, Month 3 (n= 23) | -7.91 mg/dL | Standard Deviation 45.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | TG, Month 6 (n= 27) | -2.78 mg/dL | Standard Deviation 50.39 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | TG, Month 12 (n= 26) | 2.85 mg/dL | Standard Deviation 53.05 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | TG, Month 18 (n= 27) | 12.93 mg/dL | Standard Deviation 71.09 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Bilirubin, Month 3 (n= 5) | 0.28 mg/dL | Standard Deviation 0.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Bilirubin, Month 6 (n= 9) | 0.18 mg/dL | Standard Deviation 0.45 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Bilirubin, Month 12 (n= 9) | 0.04 mg/dL | Standard Deviation 0.28 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Total Bilirubin, Month 18 (n= 7) | 0.36 mg/dL | Standard Deviation 0.74 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Direct Bilirubin, Month 3 (n= 5) | 0.08 mg/dL | Standard Deviation 0.17 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Direct Bilirubin, Month 6 (n= 9) | 0.06 mg/dL | Standard Deviation 0.28 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Direct Bilirubin, Month 12 (n= 9) | 0.03 mg/dL | Standard Deviation 0.28 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Direct Bilirubin, Month 18 (n= 7) | 0.13 mg/dL | Standard Deviation 0.21 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Glucose, Month 3 (n= 16) | 2.50 mg/dL | Standard Deviation 9 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Glucose, Month 6 (n= 21) | 4.13 mg/dL | Standard Deviation 29.9 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Glucose, Month 12 (n= 24) | 8.24 mg/dL | Standard Deviation 27.36 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Glucose, Month 18 (n= 20) | -2.10 mg/dL | Standard Deviation 26.15 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Creatinine, Month 3 (n= 60) | -0.02 mg/dL | Standard Deviation 0.2 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Creatinine, Month 6 (n= 64) | -0.21 mg/dL | Standard Deviation 1.29 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Creatinine, Month 12 (n= 60) | -0.33 mg/dL | Standard Deviation 1.6 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | Creatinine, Month 18 (n= 53) | -0.38 mg/dL | Standard Deviation 1.7 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | BUN, Month 3 (n= 22) | 1.31 mg/dL | Standard Deviation 8.87 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | BUN, Month 6 (n= 25) | 1.14 mg/dL | Standard Deviation 8.8 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | BUN, Month 12 (n= 24) | -0.18 mg/dL | Standard Deviation 8.31 |
| Monotherapy | Phase II: Mean Change From Baseline in Total Cholesterol, Low-density and High-density Lipoprotein Cholesterol, Triglycerides, Total Bilirubin, Direct Bilirubin, Glucose, Creatinine, Blood Urea Nitrogen Levels Over Time | BUN, Month 18 (n= 22) | 0.06 mg/dL | Standard Deviation 8.91 |
Secondary
Phase II: Mean VAS Fatigue Score Overtime
The VAS fatigue score ranging from 0 (symptom-free and no arthritis symptoms) to 100 (worsening in symptoms and arthritis disease activity). Higher score indicate worsening.
Time frame: At Baseline (Day of first administration of TCZ as a monotherapy) and Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase II: Mean VAS Fatigue Score Overtime | Baseline (n= 19) | 54.95 Scores on scale | Standard Deviation 25.49 |
| Monotherapy | Phase II: Mean VAS Fatigue Score Overtime | Month 3 (n= 24) | 40.58 Scores on scale | Standard Deviation 20.67 |
| Monotherapy | Phase II: Mean VAS Fatigue Score Overtime | Month 6 (n= 24) | 30.42 Scores on scale | Standard Deviation 21.2 |
| Monotherapy | Phase II: Mean VAS Fatigue Score Overtime | Month 12 (n= 17) | 33.82 Scores on scale | Standard Deviation 23.72 |
| Monotherapy | Phase II: Mean VAS Fatigue Score Overtime | Month 18 (n= 23) | 23.35 Scores on scale | Standard Deviation 25.01 |
Secondary
Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AE. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect. The AE were captured only for Phase II.
Time frame: Up to 18 months
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events | Any SAE | 5 Participants |
| Monotherapy | Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events | Any AE | 56 Participants |
| Monotherapy | Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events | AE/SAE of special interest | 10 Participants |
| Monotherapy | Phase II: Number of Participants With Any Adverse Events, Any Serious Adverse Events, Adverse Events of Special Interest, and Tubercular Events | Tubercular AE/SAE | 0 Participants |
Secondary
Phase II: Number of Participants With Retention in Therapy Without Interruption Due to Side Effects
Number of participants who retained in therapy without interruption due to side effects is reported.
Time frame: Up to 18 months
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase II: Number of Participants With Retention in Therapy Without Interruption Due to Side Effects | 103 Participants |
Secondary
Phase II: Number of Side Effects That Had Not Induced Discontinuation of Treatment
Number of side effects (AEs) that had not induced discontinuation of treatment is reported. The AEs were captured only for Phase II.
Time frame: Up to 18 months
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase II: Number of Side Effects That Had Not Induced Discontinuation of Treatment | 19 AEs |
Secondary
Phase II: Number of Side Effects That Induced Transient Interruption of Treatment
Number of side effects (AEs) that induced transient interruption of treatment is reported. The AEs were captured only for Phase II.
Time frame: Up to 18 months
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase II: Number of Side Effects That Induced Transient Interruption of Treatment | 15 AEs |
Secondary
Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18
Percentage of participant achieving SDAI remission (\< 3.3), after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy is reported. The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA which (based on 0-10 cm VAS, 0 = no disease activity and 10 = worst disease activity, where higher scores represent higher disease activity), and CRP. The SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 | Month 3 | 12.5 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 | Month 6 | 22.22 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 | Month 12 | 50.00 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participant Achieving SDAI Remission (< 3.3) at Months 3, 6, 12, and 18 | Month 18 | 36.36 Percentage of participants |
Secondary
Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18
Percentage of participants achieving CDAI remission \< 2.8, after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. CDAI is the numerical sum of four outcome parameters: TJC, SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 | Month 3 | 11.11 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 | Month 6 | 16.67 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 | Month 12 | 33.33 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving CDAI Remission (< 2.8) at Months 3, 6, 12, and 18 | Month 18 | 31.58 Percentage of participants |
Secondary
Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18
The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC (28 joints) + 0.28 square root of SJC (28 joints) + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 CRP \< 2.6 indicates disease remission and \>=2.6 to 3.2 indicates low disease activity.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 2.6, Month 3 | 18.18 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 2.6, Month 6 | 43.1 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 2.6, Month 12 | 64.15 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 2.6, Month 18 | 60.78 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 3.2, Month 3 | 32.73 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 3.2, Month 6 | 67.24 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 3.2, Month 12 | 84.91 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS28 CRP Remission (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 CRP < 3.2, Month 18 | 76.47 Percentage of participants |
Secondary
Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18
The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease. The DAS28 ESR \< 2.6 indicates disease remission and \>=2.6 to 3.2 indicates low disease activity.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 2.6, Month 3 | 14.04 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 2.6, Month 6 | 42.62 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 2.6, Month 12 | 53.57 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 2.6, Month 18 | 64.71 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 3.2, Month 3 | 24.56 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 3.2, Month 6 | 70.49 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 3.2, Month 12 | 83.93 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Achieving DAS 28 ESR (< 2.6) and Low Disease Activity (<3.2) at Months 3, 6, 12, and 18 | DAS28 ESR < 3.2, Month 18 | 80.39 Percentage of participants |
Secondary
Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18
Participants who maintained the change in DAS28 (Delta DAS28) CRP of \>=0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28-CRP is a combined index that measured RA disease activity. It is calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). It is calculated by using the formula: DAS28 CRP= 0.56 × square root of TJC 28 + 0.28 square root of SJC 28 + 0.36 × log n at (CRP+1) + 0.014 × PtGA + 0.96. The DAS28 CRP- scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); decrease in score indicated improvement of disease.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 | Month 3 | 55.36 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 | Month 6 | 56.6 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 | Month 12 | 60.78 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS 28 CRP of >= 0.6 at Months 3, 6, 12, and 18 | Month 18 | 60 Percentage of participants |
Secondary
Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18
Participants who maintained delta DAS28 ESR of \>= 0.6 after 3, 6, 12, and 18 months from the first infusion with tocilizumab as monotherapy are reported. The DAS28 ESR is a measure of the participant's disease activity calculated using TJC (28 joints), SJC (28 joints), PtGA using 0-10 cm VAS (0 = no disease activity and 10 = worst disease activity), and ESR. It is calculated by using the following formula: DAS28 ESR = 0.56 x square root of TJC + 0.28 x square root of SJC + 0.70 x log n at ESR + 0.014 x PtGA. The DAS28 ESR scores ranged from 0.49 (less disease activity) to 9.07 (maximal disease activity); where decrease in score indicated improvement of disease.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 | Month 3 | 55.00 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 | Month 6 | 67.86 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 | Month 12 | 58.82 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants Maintaining Delta DAS28 ESR >= 0.6 at Months 3, 6, 12, and 18 | Month 18 | 72.55 Percentage of participants |
Secondary
Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18
Percentage of participants with change in HAQ (Delta HAQ) of \>= 0.21 after 3, 6, 12 and 18 months from the first infusion with tocilizumab as monotherapy are reported. The HAQ consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity.
Time frame: At Months 3, 6, 12, and 18
Population: Analysis population included participants who were enrolled in Phase I and received tocilizumab as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 | Month 18 | 8.11 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 | Month 3 | 8.51 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 | Month 6 | 10.00 Percentage of participants |
| Monotherapy | Phase II: Percentage of Participants With Delta HAQ >= 0.21 at Months 3, 6, 12, and 18 | Month 12 | 13.89 Percentage of participants |
Secondary
Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy
Mean dose of corticosteroids at study entry (Baseline) is reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants who received corticosteroids were considered for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy | 4.64 milligrams | Standard Deviation 3 |
| Combination Therapy | Phase I: Mean Dose of Corticosteroids At Study Entry in Monotherapy and Combination Therapy | 4.71 milligrams | Standard Deviation 3.12 |
Secondary
Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy
Mean duration of previous treatment with a biologic drug in monotherapy are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants who received previous treatment with a biologic drug before monotherapy were considered for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy | 1254.7 Days | Standard Deviation 816 |
| Combination Therapy | Phase I: Mean Duration of Previous Treatment With a Biologic Drug in Monotherapy and Combination Therapy | 1188.3 Days | Standard Deviation 995 |
Secondary
Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy
Mean duration of treatment with a biologic drug in combination with DMARDs before monotherapy is reported in days.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants who received previous treatment with a biologic drug in combination with DMARDs before monotherapy were considered for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy | 1486.1 Days | Standard Deviation 988.4 |
| Combination Therapy | Phase I: Mean Duration of Treatment With A Biologic Drug in Combination With DMARDs Before Monotherapy | 1525.9 Days | Standard Deviation 1132.1 |
Secondary
Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy
The HAQ-DI is a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted of 20 questions in eight domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities) rated on a 4-point scale, where 0 (equals) = without difficulties; 1= with some difficulties; 2= with great difficulties; and 3= unable to perform these actions at all. The HAQ-DI scale was an average of all the scores and ranged from 0 (mild disability) to 3 (severe disability), where higher scores represents higher disease activity. Participants assessed their ability to do each task over the past seven days.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy | 0.873 Scores on scale | Standard Deviation 0.686 |
| Combination Therapy | Phase I: Mean Health Assessment Questionnaire-Disability Index in Monotherapy and Combination Therapy | 0.915 Scores on scale | Standard Deviation 0.667 |
p-value: 0.690895% CI: [-0.251, 0.167]t-test, 2 sided
Secondary
Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy
Mean of tender and swollen joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender and swollen joints was recorded on the joint assessment as no tenderness = 0 and tenderness = 1.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available tender and swollen joints at Baseline are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy | Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy | Tender Joints | 2.49 Joints | Standard Deviation 3.3 |
| Monotherapy | Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy | Swollen Joints | 1.29 Joints | Standard Deviation 2.34 |
| Combination Therapy | Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy | Tender Joints | 2.71 Joints | Standard Deviation 3.75 |
| Combination Therapy | Phase I: Mean Tender Joints and Swollen Joints as Disease Activity at Study Entry in Monotherapy and Combination Therapy | Swollen Joints | 1.20 Joints | Standard Deviation 2.45 |
Secondary
Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy
The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. The DAS28 scale ranges from 0 to 10 (0= no disease activity and 10= maximum disease activity) where higher scores represents higher disease. The DAS28 \<2.6 indicates disease remission, \>=2.6 and \<3.2 indicates Low disease activity, \>=3.2 and \<=5.1 indicates Moderate disease activity and \>5.1 indicates High disease activity. Median score for DAS28 at the study entry (Baseline) is reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available DAS28 score at Baseline are reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy | 2.51 Scores on scale |
| Combination Therapy | Phase I: Median DAS28 at Study Entry in Monotherapy and Combination Therapy | 2.77 Scores on scale |
Secondary
Phase I: Median Disease Duration in Monotherapy and Combination Therapy
The duration of disease is defined as the total time from the diagnosis of RA until the study entry.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Phase I: Median Disease Duration in Monotherapy and Combination Therapy | 125 Months |
| Combination Therapy | Phase I: Median Disease Duration in Monotherapy and Combination Therapy | 114 Months |
p-value: 0.3895Regression, Cox
Secondary
Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines
The first biologic treatment line was defined as the first use of any biologic drug in treatment of rheumatoid arthritis, regardless its association with DMARDs, the second treatment line as the subsequent use of a different biologic drug and so on for the third, fourth, fifth and sixth treatment line. According to the study protocol objectives, this analysis was performed only for Monotherapy arm.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 1 | 71 Participants |
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 2 | 35 Participants |
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 3 | 35 Participants |
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 4 | 6 Participants |
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 5 | 4 Participants |
| Monotherapy | Phase I: Number of Participants Receiving a Biologic Drug as Monotherapy at Different Treatment Lines | Treatment Line 6 | 1 Participants |
Secondary
Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy
Number of participants who received at least one previous treatment with a biologic drug as a monotherapy in both groups is reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. One participant in monotherapy group and 4 participants in combination group were not included because they had not received a previous treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy | 57 Participants |
| Combination Therapy | Phase I: Number of Participants With at Least One Previous Treatment With Biologics Drug as a Monotherapy in Monotherapy and Combination Therapy | 27 Participants |
Secondary
Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy
The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment; and PtGA and PhGA assessed on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity, where higher scores represents higher disease activity. The CDAI total score ranges from 0 (no disease activity) to 76 (maximal disease activity), where higher scores represents higher disease activity. The CDAI =\< 2.8 indicates clinical remission, \> 2.8 to 10 indicates low disease activity, \> 10 to 22 indicates moderate disease activity, and \> 22 indicates high disease activity. Number of participants with CDAI scores for both the groups at study entry (baseline) are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available CDAI score at Baseline are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Moderate disease activity | 20 Participants |
| Monotherapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Low disease activity | 28 Participants |
| Monotherapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | High disease activity | 8 Participants |
| Monotherapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Disease remission | 18 Participants |
| Combination Therapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | High disease activity | 10 Participants |
| Combination Therapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Low disease activity | 30 Participants |
| Combination Therapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Moderate disease activity | 21 Participants |
| Combination Therapy | Phase I: Number of Participants With CDAI Scores at Study Entry in Monotherapy and Combination Therapy | Disease remission | 16 Participants |
Secondary
Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy
The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (assessed on 0-10 cm) VAS; 0 = no disease activity and 10 = worst disease activity), and CRP (mg/dL). SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. Participants with available SDAI score at Baseline are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Disease remission | 19 Participants |
| Monotherapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Moderate disease activity | 22 Participants |
| Monotherapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Low disease activity | 25 Participants |
| Monotherapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | High disease activity | 6 Participants |
| Combination Therapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Low disease activity | 26 Participants |
| Combination Therapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Disease remission | 17 Participants |
| Combination Therapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | High disease activity | 6 Participants |
| Combination Therapy | Phase I: Number of Participants With SDAI Scores at Study Entry in Monotherapy and Combination Therapy | Moderate disease activity | 20 Participants |
Secondary
Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy
The percentage of participants treated with corticosteroids at enrollment is reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy | 46.05 Percentage of participants |
| Combination Therapy | Phase I: Percentage of Participants Treated With Corticosteroids at Study Entry in Monotherapy and Combination Therapy | 55.26 Percentage of participants |
Secondary
Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy
The table below shows percentage participants who started treatment with a biologic drug in monotherapy compared with percentage of participants who stopped DMARDs while taking a biologic drug in combination.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants. One participant in monotherapy group and 4 participants in combination group were not included because they had not received a previous treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy | 49.01 Percentage of Participants |
| Combination Therapy | Phase I: Percentage of Participants Who Started Treatment With a Biologic Drug in Monotherapy and Percentage of Participants Who Stopped a DMARDs While Taking a Biologic Drug in Combination Therapy | 35.81 Percentage of Participants |
p-value: 0.021Pearson's chi-squared test
Secondary
Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy
Comorbidity is the presence of previous or concomitant diseases. Percentage of participants with comorbidity is reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy | 79.61 Percentage of participants |
| Combination Therapy | Phase I: Percentage of Participants With Comorbidity in Monotherapy and Combination Therapy | 76.32 Percentage of participants |
p-value: 0.4995% CI: [0.703, 2.086]Regression, Logistic
Secondary
Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy
Participants who had prevalence with at least one previous switch, swaps or switch/swap to other therapy either monotherapy or combination therapy are reported.
Time frame: At Baseline (Day of informed consent form signed)
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Switch | 19.74 Percentage of participants |
| Monotherapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Swap | 48.68 Percentage of participants |
| Monotherapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Switch/Swap | 53.29 Percentage of participants |
| Combination Therapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Switch | 26.32 Percentage of participants |
| Combination Therapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Swap | 36.84 Percentage of participants |
| Combination Therapy | Phase I: Percentage of Participants With Prevalence of Previous Therapy Switches and Swaps in Monotherapy and Combination Therapy | Switch/Swap | 49.34 Percentage of participants |