An Open-label Study to Evaluate the Effect of MabThera in Combination With Methotrexate on Treatment Response in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 主要终点
- Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24
研究概览
简要总结
This single arm study will evaluate the efficacy and safety of MabThera in combination with methotrexate in patients with rheumatoid arthritis who have had an inadequate response to one or more anti-TNF therapies. Patients will receive MabThera 1000mg i.v. on days 1 and 15, and methotrexate (10-25mg/week p.o. or parenteral), together with methylprednisolone 100mg i.v. prior to infusion of MabThera. After week 24, eligible patients may receive re-treatment. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, 18-80 years of age;
- •rheumatoid arthritis for >=6 months;
- •receiving outpatient treatment;
- •an inadequate response to at least one anti-TNF therapy;
- •stable methotrexate for >=12 weeks.
排除标准
- •other rheumatic autoimmune disease or inflammatory joint disease;
- •previous treatment with MabThera;
- •concurrent treatment with any DMARD (apart from methotrexate), anti-TNF alpha therapy, or other biologic agent.
研究组 & 干预措施
Rituximab, Methotrexate
Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15. Participants also received methylprednisolone 100 mg, IV, 30 minutes before the infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate greater than or equal to (≥) 5 mg/week, PO, folate greater than or equal to (≥) 5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone less than or equal to (≤) 10 milligrams per day (mg/day), PO, OR equivalent corticosteroid, OR non-steroidal anti-inflammatory drugs (NSAIDs), PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
干预措施: rituximab (Drug)
Rituximab, Methotrexate
Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15. Participants also received methylprednisolone 100 mg, IV, 30 minutes before the infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate greater than or equal to (≥) 5 mg/week, PO, folate greater than or equal to (≥) 5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone less than or equal to (≤) 10 milligrams per day (mg/day), PO, OR equivalent corticosteroid, OR non-steroidal anti-inflammatory drugs (NSAIDs), PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
干预措施: Methotrexate (Drug)
Rituximab, Methotrexate
Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15. Participants also received methylprednisolone 100 mg, IV, 30 minutes before the infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate greater than or equal to (≥) 5 mg/week, PO, folate greater than or equal to (≥) 5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone less than or equal to (≤) 10 milligrams per day (mg/day), PO, OR equivalent corticosteroid, OR non-steroidal anti-inflammatory drugs (NSAIDs), PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
干预措施: Corticosteroid or NSAID (Drug)
Rituximab, Methotrexate
Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15. Participants also received methylprednisolone 100 mg, IV, 30 minutes before the infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate greater than or equal to (≥) 5 mg/week, PO, folate greater than or equal to (≥) 5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone less than or equal to (≤) 10 milligrams per day (mg/day), PO, OR equivalent corticosteroid, OR non-steroidal anti-inflammatory drugs (NSAIDs), PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
干预措施: Folate (Dietary Supplement)
结局指标
主要结局
Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24
时间窗: Week 24
ACR20 response: ≥20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and either C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).
次要结局
- Disease Activity Score Based on 28-Joint Count (DAS-28)(Baseline and Week 24)
- Tender Joint Count (TJC)(Baseline, Weeks 24 and 48)
- Patient Assessment of Pain (VAS)(Baseline, Weeks 24 and 48)
- Swollen Join Count (SJC)(Baseline, Weeks 24 and 48)
- Percentage of Participants With An American College of Rheumatology 50% Improvement Criteria (ACR50) Response at Week 24(Week 24)
- Percentage of Participants With An American College of Rheumatology 70% Improvement Criteria (ACR70) Response at Week 24(Week 24)
- Physician Global Assessment of Disease Activity (VAS)(Baseline, Weeks 24 and 48)
- C-reactive Protein (CRP) Level(Baseline, Weeks 24 and 48)
- Percentage of Participants With Change in DAS-28 From BL to Week 24 of ≥1.2(Baseline, Week 24)
- Percentage of Participants With DAS Response by European League Against Rheumatism (EULAR) Category at Week 24(Week 24)
- Patient Global Assessment of Disease Activity (VAS)(Baseline, Weeks 24 and 48)
- Erythrocyte Sedimentation Rate (ESR)(Baseline, Weeks 24 and 48)
- Modified Total Sharp-Genant Score (mTSS)(Screening and Weeks 24 and 48)
- Modified Sharp Radiographic Joint Space Narrowing Score (JSN)(Screening, Weeks 24 and 48)
- HAQ-DI Score(Baseline, Weeks 24 and 48)
- Physical Function as Assessed by Short Form 36 (SF-36)(Screening, Weeks 24 and 48)
- SF-36 Mental Component Scores(Screening, Weeks 24 and 48)
- Modified Sharp Radiographic Erosion Score (ES)(Screening, Weeks 24 and 48)