Rheumatoid Arthritis
Conditions
Brief summary
This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial compares the change in disease activity (as assessed by Disease Activity Score in 28 joints \[DAS28\] erythrocyte sedimentation rate \[ESR\]) from randomization to Week 24 post-randomization, in participants with stable low disease activity \[LDA\] (DAS28 ESR score less than or equal to \[\<=\] 3.2) who receive tocilizumab, and have been randomized to either continue or taper prednisone in a double-blinded fashion.
Interventions
DRUGPlacebo matched to prednisone
Participants will receive placebo matched to prednisone orally for 24 weeks.
DRUGPrednisone
Participants will receive prednisone either at a constant dose of 5 mg/day, or 5 mg/day with 1 mg decrements every 4 weeks orally for 24 weeks.
BIOLOGICALTocilizumab
Participants will receive tocilizumab at a dose of 162 mg once a week subcutaneously for 24 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Tocilizumab-experienced participants: * Comply with the requirements of the study protocol (including treatment on an outpatient basis) * Rheumatoid arthritis (RA) of greater than or equal to (\>=) 6 months duration diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010 ACR / European League Against Rheumatism (EULAR) criteria * Have received tocilizumab either subcutaneous (162 milligram \[mg\] once in a week) or intravenously (8 milligram per kilogram \[mg/kg\] once every 4 weeks) for the treatment of RA for at least 24 weeks prior to randomization * Have received 5 - 15 milligrams per day \[mg/day\] of glucocorticoids (prednisone or equivalent) for the treatment of RA for at least 20 weeks prior to screening * Currently receiving 5 mg/day of prednisone * Have attained and maintained LDA (DAS28 ESR score \<=3.2) or remission (DAS28 ESR score less than \[\<\] 2.6) for at least 4 weeks prior to randomization Tocilizumab-naïve participants: * Comply with the requirements of the study protocol (including treatment on an outpatient basis) * RA of \>=6 months duration diagnosed according to the revised 1987 ACR criteria or 2010 ACR / EULAR criteria * Have active RA (defined as DAS28 ESR score greater than \[\>\] 3.2) * Are considered by the investigator as inadequate responders to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs) * Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA
Exclusion criteria
General * Major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery during the study and up to 6 months after randomization * Pregnant women or nursing (breastfeeding) mothers * In females of childbearing potential, a positive serum pregnancy test at screening * Females of childbearing potential unwilling or unable to use a reliable means of contraception (for example, physical barrier \[participant or partner\], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during study treatment and for a minimum of 3 months after the last dose of tocilizumab * Body weight of \>=150 kilogram (kg) * Lack of peripheral venous access Disease-related * RA of functional Class 4, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis * Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the investigator * Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 years * Prior or current inflammatory joint disease other than RA (for example, gout, Lyme disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease), or prior or current joint infections * Previous history of primary or secondary adrenal insufficiency Previous or Concomitant Prohibited Therapy * Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening * Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD20) * Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of screening * Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4 weeks prior to screening * Previous treatment with glucocorticoids for conditions other than RA, at any dose and in any formulation used continuously for \>1 week, during the last 1 year prior to screening. Topical glucocorticoid creams or ointments for the treatment of skin conditions (for example eczema) are allowed * Immunization with a live/attenuated vaccine within 30 days prior to screening. Participants must agree not to take live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, vaccines for measles, mumps or rubella without or with varicella \[MMR or MMRV\], oral polio vaccine and vaccines for yellow fever), within 30 days before the Screening Visit, throughout the duration of the trial and for 60 days following the last dose of study drug * Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid irradiation Laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization | Baseline to Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | Baseline and Week 24 | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index is calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter (cm) visual analog scale (VAS) + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 100 mm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement. |
| Percentage of Participants With >=1 Flare | 24 weeks | Percentage of participants with \>=1 flare |
| Time to First RA Flare | Randomization to 24 weeks | The mean time of onset for the first RA flare since randomization. |
| Percentage of Visits With RA Flares | Randomization to 24 weeks | — |
| Percentage of Participants With >=1 Administration of Flare Rescue Medication | Randomization to 24 weeks | The proportion of participants with at least one administration of RA flare rescue medication. |
| Time to First Administration of Flare Rescue Medication | Randomization to 24 weeks | Time of onset of first administration of RA flare rescue medication since randomization date |
| Number of Administrations of Flare Rescue Medication | Randomization to 24 weeks | Proportion of participants who received courses of RA flare rescue medication by number of courses received. |
| Cumulative Prednisone Exposure (Dose) | Randomization to 24 weeks | In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 \* 1 mg) + (3/4 \* number of capsules taken during week 5 to 8 \* 1 mg) + (1/2 \* number of capsules taken during week 9 to 12 \* 1 mg) + (1/4 \* number of capsules taken during week 13 to 16 \* 1 mg). In continued arm, cumulative dose = (1/4 \* number of capsule taken \* 5 mg). Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone. |
| Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Randomization to Week 24 | The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24. LDA was defined as DAS28 ESR score \<= 3.2. Remission was defined as DAS28 ESR score \<= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 \<= DAS28-ESR at baseline. |
| Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control | 24 weeks | Percentage of participants who permanently discontinue study treatment due to insufficient flare control |
| Treatment Success | Week 24 | Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 \> 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts | Baseline to Week 24 | Count of tender joints based on 68 assessed joints. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain | Baseline to Week 24 | The ACR patient's assessment of pain is scored on a visual analog scale (VAS) from 0 (no pain) to 100 mm (unbearable pain). A positive change in score indicates worsening, and a negative change indicates improvement. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity | Baseline to Week 24 | The ACR patient's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity | Baseline to Week 24 | The ACR physician's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline to Week 24 | A measure of self-perceived disability containing 20 questions in eight categories and including additional section about aid from other people and devices needed to correct the disabilities. Scores range from 0 to 3, with higher scores indicating worse disability. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) | Baseline to Week 24 | Change from baseline in the acute phase reactant hsCRP |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR) | Baseline to Week 24 | Change from baseline in the acute phase reactant ESR |
| Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score | Baseline and Week 24 | The RAID is a participant-completed questionnaire specific for RA consisting of a 0-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result. A positive change in score indicates worsening, and a negative change indicates improvement. |
| Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Baseline and Week 24 | The WPAI:SHP is a 6-item questionnaire to measure performance impairment of work and regular daily activity and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score range from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity. A positive change in score indicates impairment, and a negative change indicates improvement. |
| Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24 | Randomization to Week 24 | The SDAI is the numerical sum of 5 outcome parameters: tender and swollen joint count based on a 28-joint assessment, patient and physician global assessment of disease activity according to 100-mm visual analog scale (VAS) and level of C-reactive protein in milligrams per deciliter (mg/dL, normal \<1 mg/dl). The total SDAI score range is 0-86, where higher scores indicate increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement. |
| Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts | Baseline to Week 24 | Count of swollen joints based upon 66 assessed joints. |
Countries
France, Germany, Italy, Russia, Serbia, Tunisia
Participant flow
Pre-assignment details
314 participants were enrolled in the study; 55 participants discontinued the study prior to randomization; 259 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab+Prednisone (Tapering Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. | 131 |
| Tocilizumab+Prednisone (Constant Dose) Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. | 128 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 |
| Overall Study | Lack of Efficacy | 5 | 4 |
| Overall Study | Non-compliance | 1 | 2 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Study Ended per Protocol | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Tocilizumab+Prednisone (Tapering Dose) | Total | Tocilizumab+Prednisone (Constant Dose) |
|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 14 | 54.4 Years STANDARD_DEVIATION 13.4 | 54.0 Years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants | 234 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 24 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 129 Participants | 252 Participants | 123 Participants |
| Sex: Female, Male Female | 103 Participants | 200 Participants | 97 Participants |
| Sex: Female, Male Male | 28 Participants | 59 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 131 | 0 / 128 |
| other Total, other adverse events | 46 / 131 | 21 / 128 |
| serious Total, serious adverse events | 7 / 131 | 4 / 128 |
Outcome results
Primary
Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline to Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization | 0.538 Score on a scale |
| Tocilizumab+Prednisone (Constant Dose) | Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization | -0.075 Score on a scale |
p-value: 0.00195% CI: [0.346, 0.879]ANCOVA
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index is calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter (cm) visual analog scale (VAS) + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 100 mm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | 2.663 Score on a scale |
| Tocilizumab+Prednisone (Constant Dose) | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | 0.321 Score on a scale |
p-value: 0.00695% CI: [0.661, 4.023]ANCOVA
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24
The SDAI is the numerical sum of 5 outcome parameters: tender and swollen joint count based on a 28-joint assessment, patient and physician global assessment of disease activity according to 100-mm visual analog scale (VAS) and level of C-reactive protein in milligrams per deciliter (mg/dL, normal \<1 mg/dl). The total SDAI score range is 0-86, where higher scores indicate increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Randomization to Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24 | 2.511 Score on a scale |
| Tocilizumab+Prednisone (Constant Dose) | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24 | 0.248 Score on a scale |
p-value: 0.00995% CI: [0.574, 3.953]ANCOVA
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR)
Change from baseline in the acute phase reactant ESR
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR) | 1.517 mm/hr | Standard Deviation 7.892 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR) | -0.679 mm/hr | Standard Deviation 5.433 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI)
A measure of self-perceived disability containing 20 questions in eight categories and including additional section about aid from other people and devices needed to correct the disabilities. Scores range from 0 to 3, with higher scores indicating worse disability.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI) | 0.167 Score on a scale | Standard Deviation 0.486 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.087 Score on a scale | Standard Deviation 0.527 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP)
Change from baseline in the acute phase reactant hsCRP
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) | -0.135 mg/dL | Standard Deviation 1.47 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) | -0.040 mg/dL | Standard Deviation 0.277 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain
The ACR patient's assessment of pain is scored on a visual analog scale (VAS) from 0 (no pain) to 100 mm (unbearable pain). A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain | 4.648 mm | Standard Deviation 24.315 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain | -8.010 mm | Standard Deviation 25.98 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity
The ACR patient's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity | 0.280 cm | Standard Deviation 2 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity | -0.153 cm | Standard Deviation 1.506 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity
The ACR physician's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity | 0.345 cm | Standard Deviation 1.463 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity | -0.248 cm | Standard Deviation 1.167 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts
Count of swollen joints based upon 66 assessed joints.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts | 0.129 Swollen joints | Standard Deviation 6.687 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts | -0.107 Swollen joints | Standard Deviation 1.618 |
Secondary
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts
Count of tender joints based on 68 assessed joints.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts | 0.793 Tender joints | Standard Deviation 7.764 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts | -0.330 Tender joints | Standard Deviation 2.729 |
Secondary
Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score
The RAID is a participant-completed questionnaire specific for RA consisting of a 0-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result. A positive change in score indicates worsening, and a negative change indicates improvement.
Time frame: Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score | 0.469 Score on a scale | Standard Deviation 2.109 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score | -0.220 Score on a scale | Standard Deviation 1.94 |
Secondary
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score
The WPAI:SHP is a 6-item questionnaire to measure performance impairment of work and regular daily activity and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score range from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity. A positive change in score indicates impairment, and a negative change indicates improvement.
Time frame: Baseline and Week 24
Population: Intent to Treat population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent work time missed due to problem | 4.535 Score on a scale | Standard Deviation 23.283 |
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent impairment while working due to problem | -0.851 Score on a scale | Standard Deviation 24.92 |
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent overall work impairment due to problem | 6.219 Score on a scale | Standard Deviation 29.223 |
| Tocilizumab+Prednisone (Tapering Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent activity impairment due to problem | 3.398 Score on a scale | Standard Deviation 23.786 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent activity impairment due to problem | -4.190 Score on a scale | Standard Deviation 21.608 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent work time missed due to problem | 0.572 Score on a scale | Standard Deviation 31.455 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent overall work impairment due to problem | -6.191 Score on a scale | Standard Deviation 30.531 |
| Tocilizumab+Prednisone (Constant Dose) | Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score | Percent impairment while working due to problem | -5.584 Score on a scale | Standard Deviation 23.343 |
Secondary
Cumulative Prednisone Exposure (Dose)
In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 \* 1 mg) + (3/4 \* number of capsules taken during week 5 to 8 \* 1 mg) + (1/2 \* number of capsules taken during week 9 to 12 \* 1 mg) + (1/4 \* number of capsules taken during week 13 to 16 \* 1 mg). In continued arm, cumulative dose = (1/4 \* number of capsule taken \* 5 mg). Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone.
Time frame: Randomization to 24 weeks
Population: Safety Population. The cumulative flare rescue prednisone dose population is based upon the number of participants who required rescue treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative flare rescue prednisone dose | 98.519 mg | Standard Deviation 51.921 |
| Tocilizumab+Prednisone (Tapering Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative blinded prednisone dose | 267.099 mg | Standard Deviation 40.048 |
| Tocilizumab+Prednisone (Tapering Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative prednisone dose | 287.405 mg | Standard Deviation 63.184 |
| Tocilizumab+Prednisone (Constant Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative blinded prednisone dose | 769.459 mg | Standard Deviation 175.882 |
| Tocilizumab+Prednisone (Constant Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative flare rescue prednisone dose | 121.875 mg | Standard Deviation 54.898 |
| Tocilizumab+Prednisone (Constant Dose) | Cumulative Prednisone Exposure (Dose) | Cumulative prednisone dose | 777.136 mg | Standard Deviation 172.881 |
Secondary
Number of Administrations of Flare Rescue Medication
Proportion of participants who received courses of RA flare rescue medication by number of courses received.
Time frame: Randomization to 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Number of Administrations of Flare Rescue Medication | 1 course | 15.3 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Number of Administrations of Flare Rescue Medication | 3 courses | 0 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Number of Administrations of Flare Rescue Medication | 2 courses | 4.6 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Number of Administrations of Flare Rescue Medication | >3 courses | 0.8 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Number of Administrations of Flare Rescue Medication | 0 courses | 79.4 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Number of Administrations of Flare Rescue Medication | >3 courses | 0 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Number of Administrations of Flare Rescue Medication | 0 courses | 93.8 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Number of Administrations of Flare Rescue Medication | 1 course | 3.9 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Number of Administrations of Flare Rescue Medication | 2 courses | 1.6 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Number of Administrations of Flare Rescue Medication | 3 courses | 0.8 Percentage of Participants |
Secondary
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level
The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24. LDA was defined as DAS28 ESR score \<= 3.2. Remission was defined as DAS28 ESR score \<= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 \<= DAS28-ESR at baseline.
Time frame: Randomization to Week 24
Population: Intent to Treat population. The number of participants for LDA at Week 24 and Remission at Week 24 are based upon the number with LDA at baseline and DAS28-ESR ≤ 2.6 at baseline respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | LDA at Week 24 | 73.4 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Remission at Week 24 | 61.2 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Baseline DAS28-ESR ≤ 2.6 | 78.6 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Maintained baseline activity at Week 24 | 36.6 Percentage of Participants |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | LDA at baseline | 97.7 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Maintained baseline activity at Week 24 | 54.7 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | LDA at baseline | 96.9 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | LDA at Week 24 | 83.1 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Baseline DAS28-ESR ≤ 2.6 | 76.6 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level | Remission at Week 24 | 81.6 Percentage of Participants |
Secondary
Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control
Percentage of participants who permanently discontinue study treatment due to insufficient flare control
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control | 0 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control | 0.8 Percentage of Participants |
Secondary
Percentage of Participants With >=1 Administration of Flare Rescue Medication
The proportion of participants with at least one administration of RA flare rescue medication.
Time frame: Randomization to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants With >=1 Administration of Flare Rescue Medication | 20.6 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants With >=1 Administration of Flare Rescue Medication | 6.3 Percentage of Participants |
Secondary
Percentage of Participants With >=1 Flare
Percentage of participants with \>=1 flare
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Participants With >=1 Flare | 26.0 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Participants With >=1 Flare | 10.9 Percentage of Participants |
Secondary
Percentage of Visits With RA Flares
Time frame: Randomization to 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Visits With RA Flares | >3 Visits | 0.8 Percentage of visits with flares |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Visits With RA Flares | 2 Visits | 6.9 Percentage of visits with flares |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Visits With RA Flares | 1 Visit | 16.0 Percentage of visits with flares |
| Tocilizumab+Prednisone (Tapering Dose) | Percentage of Visits With RA Flares | 3 Visits | 2.3 Percentage of visits with flares |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Visits With RA Flares | >3 Visits | 0 Percentage of visits with flares |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Visits With RA Flares | 3 Visits | 0 Percentage of visits with flares |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Visits With RA Flares | 1 Visit | 7.0 Percentage of visits with flares |
| Tocilizumab+Prednisone (Constant Dose) | Percentage of Visits With RA Flares | 2 Visits | 3.9 Percentage of visits with flares |
Secondary
Time to First Administration of Flare Rescue Medication
Time of onset of first administration of RA flare rescue medication since randomization date
Time frame: Randomization to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Time to First Administration of Flare Rescue Medication | 13.59 Weeks | Standard Deviation 6.77 |
| Tocilizumab+Prednisone (Constant Dose) | Time to First Administration of Flare Rescue Medication | 8.76 Weeks | Standard Deviation 5.26 |
Secondary
Time to First RA Flare
The mean time of onset for the first RA flare since randomization.
Time frame: Randomization to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Time to First RA Flare | 15.64 Weeks | Standard Deviation 7.13 |
| Tocilizumab+Prednisone (Constant Dose) | Time to First RA Flare | 12.11 Weeks | Standard Deviation 7.96 |
Secondary
Treatment Success
Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 \> 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission.
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab+Prednisone (Tapering Dose) | Treatment Success | 64.9 Percentage of Participants |
| Tocilizumab+Prednisone (Constant Dose) | Treatment Success | 77.3 Percentage of Participants |
p-value: 0.01895% CI: [0.285, 0.889]Regression, Logistic
p-value: 0.02195% CI: [0.714, 0.972]Cochran-Mantel-Haenszel