Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can result in toxicities, known as immune-related adverse events (irAEs), due to a hyperactivated immune system. ICI-related inflammatory arthritis has been described in literature, but herewith we introduce and characterize post-ICI-activated osteoarthritis (ICI-aOA). We conducted a multicenter, retrospective, observational study of patients with cancer treated with ICIs and diagnosed with ICI-aOA by a rheumatologist. ICI-aOA was defined by (1) an increase in non-inflammatory joint pain after ICI initiation, (2) in joints characteristically affected by osteoarthritis, and (3) lack of inflammation on exam. Cases were graded using the Common Terminology Criteria for Adverse Events (CTCAE) V.6.0 rubric for arthralgia. Response Evaluation Criteria in Solid Tumors V.1.1 (v.4.03) guidelines determined tumor response. Results were analyzed using χ2 tests of association and multivariate logistic regression. Thirty-six patients had ICI-aOA with a mean age at time of rheumatology presentation of 66 years (51-81 years). Most patients had metastatic melanoma (10/36, 28%) and had received a PD-1/PD-L1 inhibitor monotherapy (31/36, 86%) with 5/36 (14%) combination therapy. Large joint involvement (hip/knee) was noted in 53% (19/36), small joints of hand 25% (9/36), and spine 14% (5/36). Two-thirds (24/36) suffered multiple joint involvement. Three of 36 (8%) had CTCAE grade 3, 14 (39%) grade 2 and 19 (53%) grade 1 manifestations. Symptom onset ranged from 6 days to 33.8 months with a median of 5.2 months after ICI initiation; five patients suffered from ICI-aOA after ICI cessation (0.6, 3.5, 4.4, 7.3, and 15.4 months after ICI cessation). The most common form of therapy was intra-articular corticosteroid injections only (15/36, 42%) followed by non-steroidal anti-inflammatory drugs only (7/36, 20%). Twenty patients (56%) experienced other irAEs, with rheumatic and dermatological being the most common. All three patients with high-grade ICI-aOA also had another irAE diagnosis at some point after ICI initiation. ICI-aOA should be recognized as an adverse event of ICI immunotherapy. Early referral to a rheumatologist can facilitate the distinction between ICI induced inflammatory arthritis from post-ICI mechanical arthropathy, the latter of which can be managed with local therapy that will not compromise ICI efficacy.