Rheumatoid Arthritis
Conditions
Brief summary
This observational study will assess the long-term efficacy and safety of MabThera/Rituxan in routine clinical practice in patients with sero-positive rheumatoid arthritis who are non-responders or intolerant to a single tumour necrosis factor (TNF) inhibitor. Data will be collected from each patient over 2 years.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Rheumatoid arthritis positive for rheumatoid factor and/or anti-CCP * Non-responder or intolerant to single TNF-inhibitor therapy * Initiating treatment with MabThera/Rituxan
Exclusion criteria
* Contra-indications to MabThera/Rituxan therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Disease-activity Score 28-Erythrocyte Sedimentation Rate at Month 24 | Baseline (Day 0) and Month 24 | The disease-activity score 28 (DAS28) score is a measure of validated instrument for the assessment of the overall severity of RA disease activity calculated using the tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity, and erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in SJC at Month 24 | Baseline (Day 0) and Month 24 | A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/ not swollen (0) giving a total possible SJC score of 0 to 28. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in ESR at Month 24 | Baseline (Day 0) and Month 24 | The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in C-reactive Protein at Month 24 | Baseline (Day 0) and Month 24 | The C-reactive protein is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in Physician's Global Assessment of Disease Activity At Month 24 | Baseline (Day 0) and Month 24 | The Physician's Global Assessment of disease activity was assessed using a Visual Analogue Scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. |
| Mean Change From Baseline in Patient's Global Assessment of Disease Activity at Month 24 | Baseline (Day 0) and Month 24 | The Patient's Global Assessment of disease activity was assessed using VAS. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. |
| Mean Change From Baseline in Severity of Pain at Month 24 | Baseline (Day 0) and Month 24 | The patient's assessment of pain was performed using a 100 mm VAS ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. |
| Mean Change From Baseline in TJC at Month 24 | Baseline (Day 0) and Month 24 | A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28. A negative change from baseline indicates improvement. |
| Reason for Change From First TNF-inhibitor Therapy to Rituximab | At Screening | Adverse event, primary and secondary insufficient responses and monoclonal gammopathy were the reasons for starting rituximab therapy. |
| Number of Participants on Each Pattern of Re-treatment | Up to Month 24 | There are two patterns of re-treatment, namely treat-to-target and according to the clinic. Treat-to-target: a new cycle every 6 months if not in remission, with the participant receiving no new course of treatment as long as he is in remission. On demand (according to clinic): a new cycle when, in an assessment performed at least 16 weeks after the last treatment cycle, the participant shows moderate or high disease activity \[DAS28 \> 3.2 or difference in DAS28 (ΔDAS28) \> 0.6\] |
| Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions | At Months 6, 12 and 24 | An infusion reaction or injection site reaction is an event that occurs after infusion or injection which may include hypersensitivity reactions or anaphylactic reactions. |
| Number of Participants With Incidence of Infectious Events | At Months 6, 12 and 24 | Follow-up of the infectious events was done after Month 6 visit, Month 12 visit and Month 24 visit. |
| Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Up to Month 24 | An Adverse Events (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect |
| Mean Change Form Baseline in Functional Capacity at Month 24 | Baseline (Day 0) and Month 24 | The functional capacity was analyzed using Health Assessment Questionnaire-Disability Index (HAQ-DI). It is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 domains (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each domain are scored from 0 to 3 (0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do). Overall score was computed as sum of domain scores and divided by the number of domains. A total possible score ranged from 0 (best) to 3 (worst). |
Countries
Portugal
Participant flow
Recruitment details
A total of 9 participants were enrolled in one center from Portugal between 01 Jul 2010 and 30 Jun 2011. The first participant's screening visit was on 01 Jul 2010 and the last participant's last visit was on 19 Aug 2013. Although it was initially planned to involve two centers, it was only possible to involve a single center.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants with sero-positive (RF and/or CCP+) RA, who had commenced therapy with rituximab following lack of response or intolerance to a single TNF-inhibitor, were included in this arm. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 57.78 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Mean Change From Baseline in Disease-activity Score 28-Erythrocyte Sedimentation Rate at Month 24
The disease-activity score 28 (DAS28) score is a measure of validated instrument for the assessment of the overall severity of RA disease activity calculated using the tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity, and erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in Disease-activity Score 28-Erythrocyte Sedimentation Rate at Month 24 | -2.31 Scores on a scale | Standard Deviation 0.88 |
p-value: 0.0078Wilcoxon signed rank test
Secondary
Mean Change Form Baseline in Functional Capacity at Month 24
The functional capacity was analyzed using Health Assessment Questionnaire-Disability Index (HAQ-DI). It is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 domains (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each domain are scored from 0 to 3 (0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do). Overall score was computed as sum of domain scores and divided by the number of domains. A total possible score ranged from 0 (best) to 3 (worst).
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, the results are presented only for the participants with available data and who completed Month 24 visit (n=7).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change Form Baseline in Functional Capacity at Month 24 | -0.27 Scores on a scale | Standard Deviation 0.59 |
p-value: 0.2969Wilcoxon signed rank test
Secondary
Mean Change From Baseline in C-reactive Protein at Month 24
The C-reactive protein is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in C-reactive Protein at Month 24 | -8.11 Milligrams/liter | Standard Deviation 24.42 |
p-value: 0.5469Wilcoxon signed rank test
Secondary
Mean Change From Baseline in ESR at Month 24
The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in ESR at Month 24 | -28.50 Millimeter (mm)/hour | Standard Deviation 29.66 |
p-value: 0.0355Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Patient's Global Assessment of Disease Activity at Month 24
The Patient's Global Assessment of disease activity was assessed using VAS. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in Patient's Global Assessment of Disease Activity at Month 24 | -28.50 Scores on a scale | Standard Deviation 20.71 |
p-value: 0.0225Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Physician's Global Assessment of Disease Activity At Month 24
The Physician's Global Assessment of disease activity was assessed using a Visual Analogue Scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in Physician's Global Assessment of Disease Activity At Month 24 | -34.29 Scores on a scale | Standard Deviation 13.94 |
p-value: 0.0225Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Severity of Pain at Month 24
The patient's assessment of pain was performed using a 100 mm VAS ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in Severity of Pain at Month 24 | -23.15 Scores on a scale | Standard Deviation 30.48 |
p-value: 0.0904Wilcoxon signed rank test
Secondary
Mean Change From Baseline in SJC at Month 24
A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/ not swollen (0) giving a total possible SJC score of 0 to 28. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in SJC at Month 24 | -4.13 Swollen joints | Standard Deviation 2.3 |
p-value: 0.01403Wilcoxon signed rank test
Secondary
Mean Change From Baseline in TJC at Month 24
A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) and Month 24
Population: The analysis was conducted with all the participants who complied with the inclusion and exclusion criteria, thus defining full analysis set (n=9). However, data is presented only for those participants who completed Month 24 visit (n=8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Mean Change From Baseline in TJC at Month 24 | -7.5 Tender joints | Standard Deviation 6.48 |
p-value: 0.0078Wilcoxon signed rank test
Secondary
Number of Participants on Each Pattern of Re-treatment
There are two patterns of re-treatment, namely treat-to-target and according to the clinic. Treat-to-target: a new cycle every 6 months if not in remission, with the participant receiving no new course of treatment as long as he is in remission. On demand (according to clinic): a new cycle when, in an assessment performed at least 16 weeks after the last treatment cycle, the participant shows moderate or high disease activity \[DAS28 \> 3.2 or difference in DAS28 (ΔDAS28) \> 0.6\]
Time frame: Up to Month 24
Population: The analysis was conducted with all 9 participants who complied with the inclusion and exclusion criteria, thus defining the full analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants on Each Pattern of Re-treatment | Treat-to-target | 9 Participants |
| Rituximab | Number of Participants on Each Pattern of Re-treatment | On demand (according to clinic) | 0 Participants |
Secondary
Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events
An Adverse Events (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect
Time frame: Up to Month 24
Population: Safety population was used for the analysis which included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not and who complied with the criteria for inclusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Any AEs | 5 Participants |
| Rituximab | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Any SAEs | 0 Participants |
Secondary
Number of Participants With Incidence of Infectious Events
Follow-up of the infectious events was done after Month 6 visit, Month 12 visit and Month 24 visit.
Time frame: At Months 6, 12 and 24
Population: Safety population was used for the analysis which included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not and who complied with the criteria for inclusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Incidence of Infectious Events | Month 6 | 0 Participants |
| Rituximab | Number of Participants With Incidence of Infectious Events | Month 12 | 2 Participants |
| Rituximab | Number of Participants With Incidence of Infectious Events | Month 24 | 0 Participants |
Secondary
Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions
An infusion reaction or injection site reaction is an event that occurs after infusion or injection which may include hypersensitivity reactions or anaphylactic reactions.
Time frame: At Months 6, 12 and 24
Population: Safety population was used for the analysis which included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not and who complied with the criteria for inclusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions | Month 6 | 0 Participants |
| Rituximab | Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions | Month 12 | 0 Participants |
| Rituximab | Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions | Month 24 | 1 Participants |
Secondary
Reason for Change From First TNF-inhibitor Therapy to Rituximab
Adverse event, primary and secondary insufficient responses and monoclonal gammopathy were the reasons for starting rituximab therapy.
Time frame: At Screening
Population: The analysis was conducted with all 9 participants who complied with the inclusion and exclusion criteria, thus defining the full analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Reason for Change From First TNF-inhibitor Therapy to Rituximab | Adverse event - esophageal candidiasis | 1 Participants |
| Rituximab | Reason for Change From First TNF-inhibitor Therapy to Rituximab | Insufficient Response: Primary | 1 Participants |
| Rituximab | Reason for Change From First TNF-inhibitor Therapy to Rituximab | Insufficient Response: Secondary | 6 Participants |
| Rituximab | Reason for Change From First TNF-inhibitor Therapy to Rituximab | Monoclonal gammopathy | 1 Participants |