Rheumatoid Arthritis Extension Trial For Subjects Who Have Participated In Other PF-05280586 Trials (REFLECTIONS B328-04)

Study Overview
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Brief Summary
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This extension study will evaluate the safety (including immunogenicity) of treatment with rituximab-Pfizer, as well as the safety and immunogenicity after transitioning from rituximab-US or rituximab-EU to rituximab-Pfizer. This study will provide continued treatment access to subjects with active rheumatoid arthritis who have participated for at least 16 weeks in other studies in the rituximab Pfizer program.

Official Title
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EXTENSION STUDY EVALUATING TREATMENT WITH PF-05280586 VERSUS RITUXIMAB IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE PARTICIPATED IN OTHER PF-05280586 CLINICAL TRIALS

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Rituximab-Pfizer (PF-05280586) x 3 courses
* Biological: Rituximab-EU+ Rituximab-Pfizer x 2 Courses
* Biological: Rituximab-US + Rituximab-Pfizer x 2 Courses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Participated for a minimum of 16 weeks after the initiation of the last course of treatment in a previous rheumatoid arthritis study in the rituximab-Pfizer program within the past 2 months. Exclusion Criteria: Investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the study. Initiated treatment with investigational agents or other biologics (including Rituxan and MabThera) since participating in a previous rheumatoid arthritis study in the rituximab-Pfizer program.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab-Pfizer<br> | Biological: Rituximab-Pfizer (PF-05280586) x 3 courses<br>* 1000 mg intravenous infusion [IV] on Days 1 and 15 of each 24 week treatment course for up to 3 treatment courses<br>|
| Active Comparator: Rituximab-EU+Rituximab-Pfizer<br>Subjects will receive Rituximab-EU x 1 course followed by Rituximab-Pfizer x 2 courses. | Biological: Rituximab-EU+ Rituximab-Pfizer x 2 Courses<br>* Subjects will receive Rituximab-EU x 1 course followed by Rituximab-Pfizer x 2 courses. 1000 mg IV infusion of Rituximab-EU on Days 1 and 15 of a 24 week treatment course followed by 1000 mg IV infusion of PF-05280586 on Days 1 and 15 of each 24 week course for up to 2 additional treatment courses<br>|
| Active Comparator: Rituximab-US+Rituximab-Pfizer<br>Subjects will receive Rituximab-US x 1 course followed by Rituximab-Pfizer x 2 courses. | Biological: Rituximab-US + Rituximab-Pfizer x 2 Courses<br>* Subjects will receive Rituximab-US x 1 course followed by Rituximab-Pfizer x 2 courses. 1000 mg IV infusion of Rituximab-US on Days 1 and 15 of a 24 week treatment course followed by 1000 mg IV infusion of PF-05280586 on Days 1 and 15 of each 24 week course for up to 2 additional treatment courses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants by Anti-Drug Antibody (ADA) Status Using Anti-PF-05280586 Antibody Assay | Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive (+ve) for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586. | Course 1 (C1) Overall, Course 2 (C2) Overall, Course 3 (C3) Overall, and All Courses Overall. | 
| Percentage of Participants by ADA Status Using Anti-Rituximab Antibody Assay | Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586. | Course 1 Overall, Course 2 Overall, Course 3 Overall, and All Courses Overall. | 
| Percentage of Participants by Neutralizing Antibody (Nab) Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay | Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays - None of the ADA samples tested positive for NAb. | Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3). | 
| Percentage of Participants by Nab Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay Using Anti-Rituximab NAb Assay | Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays. - None of the ADA samples tested positive for NAb. | Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3). | 
| Mean Rituximab Serum Trough Concentrations | Serum samples for determination of drug concentrations were collected pre-dose concurrent with ADA sample collection. Drug concentrations in the samples were determined using a validated assay. | Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3), Follow up Months 3, 6, 9, and 12. Course 3/Week 25 is End of Treatment (EOT). | 
| Cluster of Differentiation 19 (CD19+) B Cell Count | Blood samples were assayed for CD19+ B-cell counts using laser scanning cytometry. | Weeks 1, 6, 13, and 25 (Course 1 and Course 2), Weeks 1, 13, 25 (Course 3), and Follow up Months 3, 6, and 9. | 
| Circulating Immunoglobulin G (IgG) Concentrations | Blood samples for immunoglobulin assessments were obtained to determine IgG levels in serum. | Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3). | 
| Circulating Immunoglobulin M (IgM) Concentrations | Blood samples for immunoglobulin assessments were obtained to determine IgM levels in serum. | Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3). | 
| Circulating Rheumatoid Factor (RF) Concentrations | RF is the auto-antibody directed against IgG. Blood samples were obtained to determine RF levels in serum. | Week 1 and 25 (Course 1, Course 2, and Course 3). | 
| Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Complement | Blood samples were obtained to determine anti-CCP and compliment levels in serum. | Week 1 and 25 (Course 1, Course 2, and Course 3). | 
| Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 1 | The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. | Baseline B3281001, Week 1, 6, 13, and 25 (Course 1). | 
| Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 2 | The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. | Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 3 | The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. | Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 1 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 2 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 3 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1. | Week 1, 6, 13, and 25 (Course 1 and Course 2) and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 1 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 2 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 3 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 1 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 2 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 3 | The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 1 | ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 2 | ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 3 | ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 1 | ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 2 | ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 3 | ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 1 | ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1). | 
| Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 2 | ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 3 | ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 1 | Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 2 | Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 3 | Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 1 | Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 2 | Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 3 | Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed. | Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 1 | Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. | Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 2 | Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 3 | Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 1 | Participants were asked the following question, Considering all the ways your arthritis affects you, how are you feeling today? Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 2 | Participants were asked the following question, Considering all the ways your arthritis affects you, how are you feeling today? Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 3 | Participants were asked the following question, Considering all the ways your arthritis affects you, how are you feeling today? Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 1 | The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 2 | The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 3 | The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor). | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 1 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale. | Week 1, 6, 13, and 25 (Course 1). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 2 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 3 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 
| Outcome Measure Using HAQ-DI - by the End of Course 1 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3. | Week 1, 6, 13, and 25 (Course 1). | 
| Outcome Measure Using HAQ-DI - by the End of Course 2 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3. | Week 1, 6, 13, and 25 (Course 1 and Course 2). | 
| Outcome Measure Using HAQ-DI - by the End of Course 3 | HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3. | Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extension trial, rheumatoid arthritis, rituximab