A Phase IV Multicenter, Randomized, Double-blind Study. prospeCtive Study on Intensive Early Rheumatoid Arthritis Treatment With adalimUmab: Induction of REmission and Maintenance
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 251
- 试验地点
- 1
- 主要终点
- to evaluate the proportion of subjects who achieve remission at week 52 after treatment, as defined by DAS 28 </= 2.6
研究概览
简要总结
Hypothesis: Early intensive treatment with anti-TNF agent plus methotrexate plus high dose prednisone may increase remission rate and may induce stable remission in Rheumatoid Arthritis Objective: to evaluate induction of remission using adalimumab, prednisone and methotrexate and maintenance of remission after discontinuation of adalimumab and prednisone
详细描述
Treatment group A 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + prednisone 50 mg/d tapered to 6.25 mg 6 - 12 months: Adalimumab 40 mg eow plus methotrexate 20 mg weekly group B 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + placebo 6 - 12 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly
Follow up period - Open Label phase:
Patients achieving clinical remission will be than treated only with MTX and observed for another 12 months period. Patients who do not achieve clinical remission or patients who will experience a relapse of the disease will be treated according to standard of care (SOC) modalities.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Active rheumatoid arthritis diagnosed for at least 6 weeks, but no more than 1 year, according to the revised 1987 ACR criteria
- •Naïve to treatment with MTX
- •Swollen joint count (SJC) > 8 tender joint count (TJC) > 8
- •At screening CRP > 1.5 mg/dL (15 mg/L) or ESR ≥ 28 mm/h
- •≥ 1 joint erosion or RF positivity or anti-CCP positivity
- •Age 18-70 years.
排除标准
- •Rheumatic autoimmune disease other than RA
- •Functional class IV
- •Any surgical procedure within 12 weeks prior to baseline or planned during the study.
- •Pregnancy or breast feeding.
- •Evidence of significant concomitant disease
- •Primary or secondary immunodeficiency
- •active infection of any kind
- •History of previously untreated infection with mycobacterium tuberculosis or current treatment for same.
- •History of cancer
- •Any history or presence of congestive heart failure (CHF) (New York Heart Association classification for CHF: Class III or IV).
- •Any history of myocardial infarction within 5 years.
- •History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of adalimumab or methotrexate.
- •Positive serology for hepatitis B or C indicating active infection.
- •Hemoglobin < 8.0 g/dL.
- •Absolute neutrophil count (ANC) < 1.5 x 103/L.
- •Liver function abnormality
研究组 & 干预措施
group A
- adalimumab 40 mg subcutaneous injections every other week from baseline to month 12
- methotrexate orally weekly at initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24.
- prednisone orally 50 mg daily, gradually tapered up to 6.25 mg at week 7 and stopped at month 6
干预措施: adalimumab, plus prednisone (Drug)
group B
- adalimumab 40 mg subcutaneous injections every other week from baseline to the end of month 12
- methotrexate orally oweekly at an initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24.
- placebo orally, stopped at month 6
干预措施: adalimumab plus placebo (Drug)
结局指标
主要结局
to evaluate the proportion of subjects who achieve remission at week 52 after treatment, as defined by DAS 28 </= 2.6
时间窗: 52 weeks
次要结局
- subjects who maintain stable remission at 24 months; ACR 20,50,70 at month 4,8,12,24; DAS 28 at month 4,8,12,24; HAQ at week 0,4,8,12,24; radiographic progression at months 12, 24; safety of different treatment regimens(24 months)
研究者
Carlomaurizio Montecucco
Director, Academic Division of Rheumatology, IRCCS Policlinico S. Matteo and University of Pavia
Fondazione IRCCS Policlinico San Matteo di Pavia