Clinical outcomes in cancer patients with immune checkpoint inhibitor-induced arthritis treated with methotrexate: a retrospective longitudinal monocentric pilot study.

Abstract

Objectives: Immune-mediated adverse events (irAEs) from immune checkpoint inhibitors (ICIs) often require high-dose glucocorticoids (GCs), which can promote cancer progression and counteract ICI benefits. This study evaluated the articular and oncologic clinical outcomes of ICI-induced arthritis treated with methotrexate (MTX) as a GC-sparing agent.

Methods: Adult patients with ICI-induced arthritis in 2023 were included. Arthritis was assessed using the disease activity score on 28 joints by C-reactive protein (DAS28-CRP), with follow-ups every 3 months. All patients received subcutaneous MTX, and oncologic outcomes were evaluated using RECIST 1.1 criteria after one year.

Results: Fourteen patients (median age 74.5 years) with melanoma (64.3%), colorectal cancer (14.3%), lung cancer (14.3%), or Hodgkin's lymphoma (7.1%) were treated with PD1 antagonists (92.9%) or combined with CTLA4 blockers (7.1%). Arthritis presentations included oligo-arthritis (36%), mono-arthritis (29%), polyarthritis (21%), and polymyalgia rheumatica-like syndrome (14.3%), with a mean onset of 4.7±3.7 months post-ICI. MTX was started for all at a mean dose of 9.5±1.5 mg weekly, beginning at the first rheumatology visit in 78.5% of patients. Over a mean follow-up of 12.8±4.6 months, DAS28-CRP scores improved significantly, and prednisone dosage was in all reduced (3.6 mg at V4 vs. 8.4 mg at V0, p=0.003). No major MTX-related toxicities were noted. Cancer responses at follow-up were complete (50%), partial (21.4%), stable disease (7.1%), and progression (21.5%).

Conclusions: The use of MTX in ICI-induced arthritis showed promising results in reducing GC dosages and managing the inflammatory articular activity, with no major toxicities observed over one year. These findings suggest that MTX may be a viable GC-sparing option in this context, but larger, controlled studies are needed to confirm these observations and better understand the impact on both articular and oncologic outcomes.