A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 8
- 主要终点
- Percentage of Participants in Remission at Week 28
研究概览
简要总结
The purpose of this pilot study is to investigate the possibility of discontinuing adalimumab therapy in patients with rheumatoid arthritis who are in stable remission after treatment with adalimumab in combination with methotrexate.
详细描述
Treatments with adalimumab and other tumor necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), are usually continued indefinitely. Information concerning the possibility of discontinuing anti-TNF therapy in RA patients who are in remission is limited. This is a pilot study in one country to study the effect of adalimumab discontinuation. The objective is to assess the proportion of patients with established RA in stable remission (Disease Activity Score [DAS]28 <2.6) after treatment with adalimumab in combination with methotrexate, in whom it is possible to discontinue adalimumab and to compare the remission rates among patients on sustained therapy with adalimumab + methotrexate with remission rates among patients who discontinued adalimumab.
Rheumatoid arthritis patients in stable remission (DAS28 < 2.6) treated with adalimumab + methotrexate were randomized in a 1:1 ratio to continue with adalimumab treatment or discontinue adalimumab treatment for the following 52 weeks. Subsequently an observational extension was conducted to observe patients treated at the discretion of the investigator. The observational extension period lasted until Weeks 105 - 156 (average Week 125) and consisted of one follow-up visit. Participants randomized to discontinue adalimumab therapy will be reinstituted to adalimumab if DAS28-score increases by >1.2 units from baseline and/or is scored ≥2.6 at any visit during the study and will be followed for an additional 12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Diagnosis of RA as defined by the 1987-revised American College of Rheumatology (ACR)-classification and has positive rheumatoid factor (RF) test or erosion on X-ray of hands or feet.
- •Currently treated with adalimumab and MTX (at least 10 mg/week; orally or subcutaneously).
- •In remission as defined by disease activity score (DAS)28 <2.6 for at least the past 3 months.
- •Concomitant disease-modifying anti-rheumatic drug (DMARD) or oral corticosteroid therapy has been stable for at least 3 months at study entry.
- •Female subject is either not of childbearing potential or is practicing a relevant method of birth control.
- •Subject is judged to be in good general health.
- •Subjects must be able and willing to provide written informed consent.
- •Subjects must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.
排除标准
- •Treatment with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks.
- •Oral prednisone or prednisone equivalent > 10 mg/day at baseline.
- •Joint surgery within the preceding two months.
- •History of acute inflammatory joint disease other than RA.
- •Treatment with any investigational drug within 30 days or 5 half lives, whichever is longer prior to study entry.
- •Poorly controlled medical condition, which would put the subject at risk by participation in the study.
- •History of clinically significant hematologic, renal or liver disease.
- •Diagnosis of, or history suggestive of, central nervous system (CNS) demyelinating disease.
- •History of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma of the cervix.
- •History of listeriosis, histoplasmosis, untreated tuberculosis (TB), persistent chronic infections, or recent active infections.
- •Known immune deficiency or human immunodeficiency virus (HIV).
- •Female who is pregnant or breast-feeding or considering becoming pregnant or breast feeding during the study.
研究组 & 干预措施
Adalimumab + MTX
Participants continued treatment with adalimumab 40 mg subcutaneously every other week plus methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
干预措施: adalimumab (Biological)
Adalimumab + MTX
Participants continued treatment with adalimumab 40 mg subcutaneously every other week plus methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
干预措施: methotrexate (Drug)
Methotrexate
Participants discontinued adalimumab and continued to receive methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. Participants with a significant increase in RA disease activity were re-instituted to adalimumab 40 mg every other week (rescue arm). After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.
干预措施: methotrexate (Drug)
结局指标
主要结局
Percentage of Participants in Remission at Week 28
时间窗: Week 28
Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (CRP), and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity. In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 28 were considered not to be in remission at Week 28. Also, participants who did not complete 28 weeks were considered not in remission.
Percentage of Participants in Remission at Week 28 in the Full Analysis Set 2 (FAS2)
时间窗: Week 28
Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (CRP), and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity. In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 28 were considered not to be in remission at Week 28. Also, participants who did not complete 28 weeks were considered not in remission.
次要结局
- Percentage of Participants in Remission at Week 52(Week 52)
- Number of Participants With a Flare(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52)
- Percentage of Participants With Response to Adalimumab Treatment (DAS28 <2.6 or DAS28 Decrease >1.2 Units) After a Flare(1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy)
- European Quality of Life-5 Dimensions (EQ-5D) Mobility Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- Percentage of Participants With Response to Adalimumab Treatment (Return to Baseline DAS28 + ≤ 10%) After a Flare(1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy)
- European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- Work Instability Score (WIS) for RA: I'm Finding my Job is About All I Can Manage(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: The Stress of my Job Makes my Arthritis Flare(Baseline and at Weeks 12, 28, 52, and 104-156)
- Percentage of Participants in Remission at Week 52 (FAS2)(Week 52)
- Health Assessment Questionnaire (HAQ) Total Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- European Quality of Life-5 Dimensions (EQ-5D) Self-care Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- Work Instability Score (WIS) for RA: I Have Used my Vacation so That I Don't Have to Take Sick Leave(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I've Got to Watch How Much I do Certain Things at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Have Great Difficulty Opening Some of the Doors at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Have to Allow Myself Extra Time to do Some Jobs(Baseline and at Weeks 12, 28, 52, and 104-156)
- European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- Work Instability Score (WIS) for RA: I'm Getting up Earlier Because of Arthritis(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Get Very Stiff at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: If I Don't Reduce my Hours I May Have to Give up Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: It's Very Frustrating Because I Can't Always do Things at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Feel I May Have to Give up Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale by Visit(Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit))
- Work Instability Score (WIS) for RA: I'm Finding Any Pressure on my Hands is a Problem(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Get Good Days and Bad Days at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Can Get my Job Done, I'm Just a Lot Slower(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I am Very Worried About my Ability to Keep Working(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Have Pain or Stiffness All the Time at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Don't Have the Stamina to Work Like I Used to(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Push Myself to go to Work Because I Don't Want to Give in to the Arthritis(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: Sometimes I Can't Face Being at Work All Day(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Have to Say No to Certain Things at Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I Get on With the Work But Afterwards I Have a Lot of Pain(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: When I'm Feeling Tired All the Time Work is a Grind(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Instability Score (WIS) for RA: I'd Like Another Job But I am Restricted to What I Can do(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Productivity and Activity Impairment (WPAI): Currently Employed(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Productivity and Activity Impairment (WPAI): Hours Missed From Work(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Productivity and Activity Impairment (WPAI): Hours Missed From Work for Other Reasons(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Productivity and Activity Impairment (WPAI): Hours Worked(Baseline and at Weeks 12, 28, 52 and 104-156)
- Work Productivity and Activity Impairment (WPAI): Work Productivity(Baseline and at Weeks 12, 28, 52, and 104-156)
- Work Productivity and Activity Impairment (WPAI): Daily Activities(Baseline and at Weeks 12, 28, 52, and 104-156)
- Change From Baseline in Radiological Modified Total Sharp Score(Baseline, Week 52, and Weeks 104-156)