Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: A Pragmatic Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- percentage of participants on prednisone
研究概览
简要总结
This study will examine the effectiveness of administering adalimumab as a treatment for patients in the early stages of steroid-dependent immune checkpoint Inhibitor associated inflammatory arthritis (ir-IA). Adalimumab (ADA) is a TNF inhibitor (TNFi) that is well established as a standard of care treatment for numerous types of inflammatory arthritis. It is hoped that adalimumab at the early stages of the ir-IA will reduce the symptoms and therefore reduce the need for steroids. This study is a pragmatic randomized clinical trial. Patients will be randomized 1:1 to each treatment group. To evaluate the steroid sparing effect of early induction six doses of Adalimumab will be administered to patients in the study treatment arm as compared to the usual standard of care of a predefined corticosteroid regimen and taper at 12 weeks administered in the control group.
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
- 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
- •• Patients are deemed eligible for study participation if they meet all the following:
- •Adult patients (age 18 or older)
- •New (within the last 6 months prior to enrollment) inflammatory arthritis defined by any of the following at the time of screening (either on physical exam or by ultrasound) by a certified rheumatologist:
- •1 or more swollen joints OR
- •1 or more tenosynovitis OR
- •1 or more enthesitis
- •Arthritis onset with taking ICI therapy OR within 4 weeks of stopping ICI therapy including CTLA-4, PD-1, and PDL-1 inhibitors
- •Initiation of ICI therapy must predate the onset of inflammatory arthritis
- •Glucocorticoid dependence at any time before enrolment, defined by either:
- •Patients requiring prednisone at a dose of at least 10 mg daily (or equivalent) OR
- •Patients for whom at least 1 glucocorticoid taper failed to control the disease activity
- •Negative tuberculosis (TB) status within the past 12 months (TB skin test or quantiferon) for the patients in the adalimumab group. If not available, the status should be confirmed within 6 months of enrollment in the study (adalimumab group only)
- •Written informed consent provided by patient or power of attorney
排除标准
- •Patients are excluded if they meet any of the following:
- •Previous diagnosis of inflammatory arthritis or other rheumatic disease (prior to current acute episode)
- •Including but not limited to: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, systemic vasculitis, undifferentiated inflammatory arthritis, undifferentiated connective tissue disease
- •Tenosynovitis, synovitis or enthesitis attributed to another cause, fracture or acute gout/CPPD flare.
- •Presence of a contraindication to adalimumab therapy
- •Any of the following in the 7 days prior to initiation of adalimumab: positive tuberculin skin test (>5mm induration within 48 to 72 hours) or positive quantiferon, evidence of untreated active infection including fungal infection, opportunistic infection, hepatitis B/C, or HIV
- •Personal history of congestive heart failure
- •Personal or family history of demyelinating neurologic disease
- •History of previous TNF inhibitor use
- •Current use of other disease modifying agents including: Chloroquine, Sulfasalazine, Azathioprine, 6-MP, and Leflunomide
- •Presence of a concomitant non-rheumatic irAE which required systemic immunosuppression within the past 3 months e.g. pneumonitis, hepatitis, colitis, scleritis, nephritis
- •Require chronic steroid treatment for adrenal insufficiency or another medical reason other than ir-IA
- •Pregnancy, breastfeeding or childbearing potential without practicing highly effective contraception.
- •Inability to participate in follow-up visits
研究组 & 干预措施
Standard of care group
Baseline oral prednisone dose taken daily for one week, then weekly prednisone taper for 12 weeks or until stopped according to the 12-week Glucocorticoid Tapering Schedule
干预措施: Prednisone (Drug)
Adalimumab group
Adalimumab 40mg SC every 2 weeks x 6 doses + Baseline oral prednisone dose taken daily for one week, then weekly prednisone taper for 12 weeks or until stopped according to the 12-week Glucocorticoid Tapering Schedule.
干预措施: Adalimumab (Drug)
Standard of care group
Baseline oral prednisone dose taken daily for one week, then weekly prednisone taper for 12 weeks or until stopped according to the 12-week Glucocorticoid Tapering Schedule
干预措施: Adalimumab (Drug)
结局指标
主要结局
percentage of participants on prednisone
时间窗: at 12 weeks
Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.
Cumulative prednisone dose
时间窗: at 12 weeks
Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1.
次要结局
- percentage of participants on prednisone(24 weeks)
- Cumulative prednisone dose(24 weeks)
- percentage of dose reduction of prednisone(At 12 and 24 weeks)
- percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)(at 12 and 24 weeks)
- percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator)(at 12 and 24 weeks)
研究者
Tom Appleton
Principal Investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's