SMART Study: A Study of Re-treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on Anti-TNF Alfa Therapy

• ClinicalTrials.gov Identifier: NCT01126541
• Recruitment Status: Completed
• First Posted: May 19, 2010
• Results First Posted: September 15, 2014
• Last Update Posted: September 15, 2014
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: rituximab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparative Study to Assess the Effect of Retreatment With 2 Doses of MabThera on Disease Activity Score in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response or Intolerance to antiTNF-alfa Therapy.(SMART)
• Study Start Date: September 2006
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; 1000 mg IV rituximab	Drug: rituximab; Arm A: 1000 mg IV (one infusion) every 2 months \nArm B: 2 x 1000 mg IV (2 infusions) every 2 months; Other Name: MabThera/Rituxan
Experimental: B; 2 x 1000 mg IV rituximab	Drug: rituximab; Arm A: 1000 mg IV (one infusion) every 2 months \nArm B: 2 x 1000 mg IV (2 infusions) every 2 months; Other Name: MabThera/Rituxan

Outcome Measures

Primary Outcome Measures :

1. Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104 [ Time Frame: Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and serum CRP levels (measured in milligrams per liter [mg/L]) at each visit. Joint counts included swollen joint count (SJC) and tender joint count (TJC). Total score range was 0 to 9.4; a higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity, and less than (<)2.6 equals (=) remission. The AUC of all DAS28-CRP values between Day 1 and Week 104 (15 values of protocol visits) was calculated using the trapeze method (AUC between t1 and t2=(t2-t1)*((DAS28-CRP at t1 + DAS28-CRP at t2)/2). The true visit dates were used to calculate the time between 2 DAS28-CRP evaluations. All the AUC were censored at Week 104 (linear extrapolation using the 2 last DAS28-CRP values (Weeks 96 and 104) to obtain the "true" DAS28-CRP value at the "true" Week 104).

Secondary Outcome Measures :

1. DAS28-CRP During the Initial Treatment [ Time Frame: Days 1 and 15, and Weeks 6, 12, and 24 ]
   Mean DAS28-CRP at Week 24 of the Initial Treatment study. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity, and <2.6=remission.
2. DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course [ Time Frame: Day 1, 24 weeks following each infusion up to 72 Weeks ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity, and <2.6=remission.
3. Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2) [ Time Frame: Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment ]
   Percentage of participants with clinical remission and low disease activity as measured by DAS28-CRP for Arm A and Arm B at Week 24 of the Initial Treatment, at 24 weeks after first re-treatment, and at 24 weeks after second retreatment. DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity and <2.6 = remission.
4. DAS28-CRP AUC Weighted Time [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity, and <2.6=remission.
5. Time to Achieve DAS28-CRP Remission After the First Course [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP <2.6=remission.
6. Time to Achieve DAS28-CRP Remission After Retreatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP <2.6=remission.
7. Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
8. Time to Achieve DAS28-CRP ≤3.2 After Retreatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
9. Duration of DAS28-CRP Remission After the First Course of Treatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
   DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP <2.6=remission.
10. Duration of DAS28-CRP Remission After Retreatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
    DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP <2.6=remission.
11. Duration of DAS28-CRP ≤3.2 After the First Course of Treatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
    DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
12. Duration of DAS28-CRP ≤3.2 After Retreatment [ Time Frame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104 ]
    DAS28-CRP was based on joint counts, overall participant assessment, and the serum CRP level at each visit. Joint counts included SJC and TJC using the 28 joints count and CRP (mg/L). Total score range=0 to 9.4; a higher score indicated more disease activity. A DAS28-CRP score of ≤3.2 implied low disease activity.
13. Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70) [ Time Frame: Week 24 of the initial treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment ]
    ACR20/50/70 response defined as ≥20%, 50%, or 70% improvement, respectively, in TJC and SJC, and ≥20%, 50%, or 70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: Patient Global Assessment of Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity (on a visual analog scale [VAS]); Health Assessment Questionnaire-Disability Index (HAQ-DI); and CRP.
14. Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category [ Time Frame: Day 15, Weeks 6, 12, and 24 ]
    DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline >1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline >1.2 with a DAS28 score of >3.2 to ≤ 5.1 or change from baseline >0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline >0.6 and ≤ 1.2 with a DAS28 score of >5.1.
15. Percentage of Participants Achieving a Response During Retreatment by EULAR Category [ Time Frame: Week 24, 24 weeks after 1st retreatment, 24 weeks after 2nd retreatment ]
    DAS28-based EULAR response criteria were used to measure individual response as no response, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders = change from baseline >1.2 with a DAS28 score of ≤3.2; moderate responders = change from baseline >1.2 with a DAS28 score of >3.2 to ≤ 5.1 or change from baseline >0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = change from baseline ≤0.6 or change from baseline >0.6 and ≤ 1.2 with a DAS28 score of >5.1.
16. Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment [ Time Frame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment ]
    RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 international units per milliliter (IU/mL) is considered positive.
17. Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment [ Time Frame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment ]
    Anti-CCP antibodies are auto antibodies (antibodies directed against 1 or more of an individual's own proteins) that are frequently detected in the blood of rheumatoid arthritis participants. Anti-CCP antibodies value higher than 10 U/mL is considered positive.
18. Physician's Global Assessment of Disease Activity [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    The Physician's Global Assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal VAS by the physician. 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). Physicians were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high disease activity).
19. Patient Global Assessment of Disease Activity [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    The Patient's Global Assessment of Disease Activity is assessed on a 0 to 100 mm horizontal VAS by the participant. 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). Higher values correspond to worst state of participant (high disease activity).
20. Patient's Global Assessment of Pain [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels).
21. Participant Assessment of Fatigue [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    Participants were asked to rate their level of fatigue over the last 7 days on a 100-mm VAS. The left-hand extreme of the line equals 0 mm, and is described as "no fatigue" and the right-hand extreme equals 100 mm as "extreme fatigue". Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high levels of fatigue).
22. Cortisone Intake AUC (Time- and Weight-Weighted) [ Time Frame: Day 1 (each infusion), Week 24, Week 104 ]
    All cortisone intakes (in mg) were taken into account (oral, IV [including the cortisone administration before the rituximab infusion], intramuscular, and intra-articular).
23. Total Mean Dose of Cortisone Between Week 24 and Week 104 [ Time Frame: Week 24 to Week 104 ]
    All cortisone intakes were taken into account, including oral, IV (including the cortisone administration before the rituximab infusion), intramuscular and intra-articular.
24. HAQ-DI Scores [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
25. Short Form 12 (SF-12) Physical Health Composite Score [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    Physical and Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
26. SF-12 Mental Health Composite Score [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    Mental Health Composite Scores of SF-12 were computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
27. Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index [ Time Frame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment ]
    The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The SLP6 index is comprised of 6 items: provides a summary of sleep problems and contains questions from the sleep disturbance, sleep adequacy, respiratory impairment, and somnolence domains. The SLP6 index score ranges between 0 and 100, with higher values corresponding to more sleep problems.
28. Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS) [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of disease activity they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".
29. Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    The Patient's Global Assessment of Disease Activity assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. 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). Higher values correspond to worst state of participant (high disease activity).
30. Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Participants were asked how their disease activity had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more disease activity.
31. Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII [ Time Frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment ]
    The Patient's Global Assessment of Disease Activity was assessed in participants reporting MCII on a 0 to 100 mm horizontal VAS by the participant. 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). Higher values correspond to worst state of participant (high disease activity).
32. Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of function they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of function they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".
33. HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    HAQ-DI was assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of disease activity they had during the last 48 hours). HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
34. Percentage of Participants With MCII in Functioning [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Participants were asked how their functioning had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse.
35. Change From Baseline in HAQ-DI in Participants With MCII [ Time Frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment ]
    HAQ-DI was assessed in participants with MCII. HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3 extreme difficulty.
36. Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, participants who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".
37. Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Patient Global Assessment of Pain assessed in participants reporting acceptable symptom state using PASS (acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours) on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". Higher values correspond to worst state of participant (high pain levels).
38. Percentage of Participants With MCII in Pain [ Time Frame: Week 24, 12 and 24 weeks after 1st retreatment ]
    Participants were asked how their pain had been during the last 48 hours compared to baseline. Those participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse pain.
39. Change From Baseline in Patient Global Assessment of Pain in Participants With MCII [ Time Frame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment ]
    The participants assessed their pain over the past 24 hours on a 0 to 100 mm horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". Participants were asked to mark the line and the distance from the left edge was measured. Higher values correspond to worst state of participant (high pain levels).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult patients >18 years of age
• RA for >=6 months
• Receiving outpatient treatment
• Ongoing treatment with methotrexate for >=3 months, stable for >=1 month
• Inadequate response or intolerance to etanercept, infliximab or adalimumab

Exclusion Criteria:

• Previous treatment with MabThera
• Concurrent treatment with any anti TNF-alfa therapy or biologic therapy
• Previous treatment with any investigational cell-depleting therapies

Contacts and Locations

Locations

France

Abbeville, France, 80142

Agen, France, 47923

Aix En Provence, France, 13616

Aix Les Bains, France, 73106

Amiens, France, 80054

Belfort, France, 90016

Berck, France, 62600

Bobigny, France, 93009

Bois-guillaume, France, 76233

Boulogne-billancourt, France, 92104

Brest, France, 29609

Caen, France, 14033

Cahors, France, 46005

Clermont-ferrand, France, 63003

Corbeil-essonnes, France, 91106

Echirolles, France, 38434

La Roche Sur Yon, France, 85925

Le Kremlin Bicetre, France, 94275

Libourne, France, 33505

Lievin, France, 62800

Lille, France, 59037

Limoges, France, 87042

Lomme, France, 59462

Lyon, France, 69365

Marseille, France, 13013

Montivilliers, France, 76290

Montpellier, France, 34295

Nantes, France, 44035

Narbonne, France, 11108

Nice, France, 06202

Paris, France, 75019

Paris, France, 75475

Paris, France, 75571

Paris, France, 75651

Paris, France, 75674

Paris, France, 75679

Paris, France, 75877

PAU, France, 64046

Perpignan, France, 66046

Pessac, France, 33600

Pierre Benite, France, 69495

Poitiers, France, 86021

Reims, France, 51100

Rennes, France, 35203

Saint-etienne, France, 4200

Strasbourg, France, 67098

Toulon, France, 83100

Toulouse, France, 31054

Toulouse, France, 31059

Valence, France, 26000

Valenciennes, France, 59322

Vandoeuvre-les-nancy, France, 54511

Vannes, France, 56017

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Jong TD, Sellam J, Agca R, Vosslamber S, Witte BI, Tsang-A-Sjoe M, Mantel E, Bijlsma JW, Voskuyl AE, Nurmohamed MT, Verweij CL, Mariette X. A multi-parameter response prediction model for rituximab in rheumatoid arthritis. Joint Bone Spine. 2018 Mar;85(2):219-226. doi: 10.1016/j.jbspin.2017.02.015. Epub 2017 Mar 28.

Sellam J, Riviere E, Courties A, Rouzaire PO, Tolusso B, Vital EM, Emery P, Ferraccioli G, Soubrier M, Ly B, Hendel Chavez H, Taoufik Y, Dougados M, Mariette X. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016 Dec 13;18(1):294. doi: 10.1186/s13075-016-1190-z. Erratum In: Arthritis Res Ther. 2017 Jan 23;19(1):11.

Sellam J, Rouanet S, Hendel-Chavez H, Miceli-Richard C, Combe B, Sibilia J, Le Loet X, Tebib J, Jourdan R, Dougados M, Taoufik Y, Mariette X. CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2013 Sep;65(9):2253-61. doi: 10.1002/art.38023.

Mariette X, Rouanet S, Sibilia J, Combe B, Le Loet X, Tebib J, Jourdan R, Dougados M. Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial. Ann Rheum Dis. 2014 Aug;73(8):1508-14. doi: 10.1136/annrheumdis-2013-203480. Epub 2013 May 30.

Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y. Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.

Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, Combe B, Le Loet X, Tebib J, Sibilia J, Taoufik Y, Dougados M, Mariette X. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011 Apr;63(4):933-8. doi: 10.1002/art.30233.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01126541
• Other Study ID Numbers: ML19895
• First Posted: May 19, 2010
• Results First Posted: September 15, 2014
• Last Update Posted: September 15, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents