Early Adalimumab Induction for Immune Checkpoint Inhibitor Associated Inflammatory Arthritis

ConditionsInflammatory Arthritis Immune-related Adverse Event

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorTom Appleton

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult patients (age 18 or older)

1 or more swollen joints OR

1 or more tenosynovitis OR

1 or more enthesitis

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

Adalimumab
Drug
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.
Prednisone
Drug
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 QD, the dose will be rounded up or down, as clinically indicated per investigator discretion, to the nearest of these doses. The prednisone taper regimen is tailored to each patient based on the starting dose over a 12-week period.

Treatment groups

30 Participants

are divided into 2 treatment groups

Group A: Standard of care groupActive comparator 2 interventions

Group B: Adalimumab groupActive comparator 1 intervention

Trial outcomes

Primary outcomes

percentage of participants on prednisone

Definition of success: Thirty percent fewer participants on prednisone in Group 2 vs Group 1.

Time frame

at 12 weeks

Cumulative prednisone dose

Definition of success: Thirty percent reduction in the cumulative dose of steroids in Group 2 compared to Group 1.

Time frame

at 12 weeks

Secondary outcomes

percentage of participants on prednisone

Definition of success: Thirty percent difference between the two groups

Time frame

24 weeks

Cumulative prednisone dose

Definition of success: Thirty percent difference between the two groups

Time frame

24 weeks

percentage of dose reduction of prednisone

Definition of success: Thirty percent difference between the two groups

Time frame

At 12 and 24 weeks

percentage of participants with immune-related inflammatory arthritis in remission (based on opinion of investigator)

Definition of success: Thirty percent difference between the two groups

Time frame

at 12 and 24 weeks

Other outcomes

percentage of participants with persistent active synovitis/tenosynovitis (yes/no)

Differences between treatment groups ≥20% will be considered significant

Time frame

at 12 and 24 weeks

percentage of participants treated with methotrexate and/or hydroxychloroquine

Differences between treatment groups ≥20% will be considered significant

Time frame

at 12 and 24 weeks

MDGA (MD global assessment) of arthritis 0 to 10

Differences between treatment groups ≥20% will be considered significant

Time frame

at weeks 12 and 24

Participant reported pain on a visual analog scale from 0 to 10.

Enhancement of quality of life due to ADA will be defined as 50% improvement in any of these readouts in ≥50% of participants at weeks 12 and 24 compared to Group 1.

Time frame

at weeks 12 and 24