A Randomized, Placebo Controlled, Double-blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate, Compared to Methotrexate Monotherapy, in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 511
- 主要终点
- Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
研究概览
简要总结
This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo + methotrexate (MTX)
Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Folate (Drug)
Placebo + methotrexate (MTX)
Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methotrexate (Drug)
Placebo + methotrexate (MTX)
Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methylprednisolone (Drug)
Placebo + methotrexate (MTX)
Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Placebo (Drug)
Placebo + methotrexate (MTX)
Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Rituximab (Drug)
Rituximab 2 x 0.5 g + MTX
Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Folate (Drug)
Rituximab 2 x 0.5 g + MTX
Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methotrexate (Drug)
Rituximab 2 x 0.5 g + MTX
Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methylprednisolone (Drug)
Rituximab 2 x 0.5 g + MTX
Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Rituximab (Drug)
Rituximab 2 x 1.0 g + MTX
Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Folate (Drug)
Rituximab 2 x 1.0 g + MTX
Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methotrexate (Drug)
Rituximab 2 x 1.0 g + MTX
Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Methylprednisolone (Drug)
Rituximab 2 x 1.0 g + MTX
Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
干预措施: Rituximab (Drug)
结局指标
主要结局
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
时间窗: Baseline and Week 24
To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements: * Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (assessed using a 100 mm VAS); * Patient's assessment of pain (assessed using a 100 mm VAS); * Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3); * Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR). Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
次要结局
- Percent Change From Baseline in Tender Joint Count(Baseline, Week 24 and Week 48)
- Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24(Baseline and Week 24)
- Percent Change From Baseline in Patient's Pain Assessment(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain Score(Baseline, Week 24 and Week 48)
- Percentage of Participants With an ACR50 Response at Week 24(Baseline and Week 24)
- Percentage of Participants With an ACR70 Response at Week 24(Baseline and Week 24)
- Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24(Baseline and Week 24)
- Percent Change From Baseline in C-Reactive Protein(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Swollen Joint Count(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Patient's Global Assessment of Disease Activity(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Short Form 36 Health Survey (SF-36) Summary Scores (Physical and Mental Components)(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Physician's Global Assessment of Disease Activity(Baseline, Week 24 and Week 48)
- Percent Change From Baseline in Erythrocyte Sedimentation Rate(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain Score(Baseline, Week 24 and Week 48)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scores(Baseline, Week 24 and Week 48)
- Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24(Week 24)
- Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain Score(Baseline, Week 24 and Week 48)
- Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48(Baseline and Week 48)
- Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24(Baseline and Week 24)
- Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48(Week 48)
- Percentage of Participants With an ACR50 Response at Week 48(Baseline and Week 48)
- Percentage of Participants With an ACR70 Response at Week 48(Baseline and Week 48)
- Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48(Baseline and Week 48)