Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

Tom Appleton

Status and phase: Enrolling; Phase 2

Conditions: Inflammatory Arthritis; Immune-related Adverse Event

Treatments: Drug: Adalimumab; Drug: Prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT06037811

CanRIO ADA2023

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• • 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
  • Arthritis either does not respond completely to prednisone doses of 10mg (equivalent) OR recurs with prednisone taper below 10mg daily.
  • 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Standard of care group

Active Comparator group

Description:

Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.

Treatment:

Drug: Prednisone

Adalimumab group

Active Comparator group

Description:

Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses (12 weeks) + Prednisone 10 mg daily for 2 weeks, tapering by 2.5 mg every 2 weeks until stopped.

Treatment:

Drug: Prednisone

Drug: Adalimumab