Clinical phenotypes and management of patients with musculoskeletal immune-related adverse events treated with immune checkpoint inhibitors.

Abstract

e14625 Background: Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) can cause systemic toxicities, including musculoskeletal manifestations such as ICI-inflammatory arthritis (ICI-IA), polymyalgia rheumatica (PMR)-like syndrome, and myositis. Recently, improved descriptions of arthritis phenotypes have included osteoarthritis (aOA), which involves heightened pain in joints affected by OA without evidence of significant inflammation.This study examines clinical features and DMARD management of ICI-associated arthritides (ICI-IA, PMR-like syndrome, and aOA). Methods: We retrospectively analyzed 50 patients who developed musculoskeletal irAEs post-ICI therapy, leading to rheumatology referral at a tertiary center (July 2016–June 2019). Myositis cases were excluded. Data included demographics, cancer type, ICI regimen, symptom onset, autoantibodies, joint involvement, and arthritis treatment. Results: The cohort included 29 men (58%) and 21 women (42%). Common cancers were melanoma (76%) and non-small cell lung cancer (12%). 98% received anti-PD-1/PD-L1, and 46% received anti-CTLA-4. Five had pre-existing autoimmune rheumatic disease. 78% had other irAEs, most commonly rash (30%), colitis (18%), hepatitis (16%), hypothyroidism (16%), and pneumonitis (12%). Musculoskeletal symptoms emerged a median of 84 days (IQR 34-236) post-ICI initiation. Autoantibody testing was notable for 6% RF/CCP(+) and 16% ANA(+). Joint involvement patterns included polyarthritis (44%), oligoarthritis (40%), and monoarthritis (14%), with 38% of all patients showing symmetric involvement. Most affected joints were the knees (62%), PIPs (40%), shoulders (40%), wrists (40%), MCPs (36%), ankles (34%), hips (28%), elbows (22%). Musculoskeletal phenotypes included ICI-IA (58%), aOA (38%), crystalline arthritis (12%), and PMR-like syndrome (10%), with some presenting multiple types. Although shoulder pain was common, only 15% had PMR-like syndrome. Treatment included NSAIDs (70%) and oral steroids (54%). The majority of patients presented with grade 2-3 toxicity, and 56% required the initiation of DMARDs, including biologics. Among these, hydroxychloroquine was the most frequently prescribed (44%). Median DMARD duration was 123 weeks (IQR 33-233), with a median of 2 DMARDs per patient (IQR 1-3). Conclusions: Musculoskeletal irAEs present variably, with knee involvement, oligo/polyarthritis, and inflammatory arthritis being common. Although PMR-like syndrome is often suspected in shoulder pain, 85% of those in our cohort had ICI-IA, aOA, or mechanical causes (e.g., rotator cuff tear). Musculoskeletal toxicity is often persistent, requiring prolonged DMARD therapy ( > 2 years). Close oncology-rheumatology collaboration is essential.