Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

Официальное название

Early Adalimumab Induction for Treatment of Steroid Dependent Immune Checkpoint Inhibitor Associated Inflammatory Arthritis: A Pragmatic Randomized Clinical Trial

Обзор

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.

Вмешательства

• Препарат Adalimumab
  Participants will be randomized 1:1 (non-blinded) to receive either adalimumab (40 mg subcutaneous every 2 weeks for 12 weeks) and prednisone vs prednisone alone. Addition of methotrexate (MTX) and/or hydroxychloroquine (HCQ) is permitted, as needed, at the discretion of the treating rheumatologist. No additional conventional synthetic, targeted synthetic or biologic DMARDs are permitted during the trial.
• Препарат Prednisone
  Prednisone as per standard of care. The 12-week glucocorticoid regimen and taper will be standardized between the groups. At Baseline, all participants will be switched to oral prednisone dose at 10, 20, 30, 40, 50, or 60 mg once daily. The initial dose of prednisone is at the discretion of the investigator, based on disease severity and comorbid medical conditions, at a minimum of 10 mg once daily at Baseline. At Baseline, if a participant is on a dose other than 10, 20, 30, 40, 50, or 60 mg Q

Первичные конечные точки

• percentage of participants on prednisone [Срок оценки: at 12 weeks]
• Cumulative prednisone dose [Срок оценки: at 12 weeks]

Вторичные конечные точки (5)

• percentage of participants on prednisone [Срок оценки: 24 weeks]
• Cumulative prednisone dose [Срок оценки: 24 weeks]
• percentage of dose reduction of prednisone [Срок оценки: At 12 and 24 weeks]
• percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator) [Срок оценки: at 12 and 24 weeks]
• percentage of participants with immune-related inflammatory arthritis resolution (based on opinion of investigator) [Срок оценки: at 12 and 24 weeks]

Критерии участия

Критерии включения

• • 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• St. Joseph's Health Care — London

Идентификаторы

NCT: NCT06037811 · CanRIO ADA2023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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