Clinical Phenotypes, Treatment, and Outcomes of Rheumatic Immune-Related Adverse Events in Patients Treated With...

Immune checkpoint inhibitors (ICIs) induce a broad range of immune-related adverse events (irAEs), including rheumatic manifestations. Evidence from dedicated rheumatology cohorts on the clinical spectrum, severity, treatment, and outcomes of rheumatic irAEs (rh-irAEs) remains limited. We aimed to describe clinical phenotypes, treatment, and outcomes of rh-irAEs in a national registry.

The German ERIN Registry (Registry for the Documentation of Rheumatic Immunotherapy-Related Adverse Events) is a multicenter observational registry of adults receiving ICIs. Rh-irAEs were classified using a rheumatology-oriented phenotype-based framework. Variables included demographics, oncological characteristics, treatments, and outcomes. Severity was graded by Common Terminology Criteria for Adverse Events version 5.0. Univariate analyses identified predictors of second-line systemic therapy.

As of January 1, 2026, 60 patients (56.7% men; median age 66 years) were included. Predominant malignancy was melanoma (40.0%). The leading phenotype was rheumatoid arthritis-like polyarthritis (41.7%), followed by polymyalgia rheumatica-like (18.3%) and peripheral spondyloarthritis-like syndrome (11.7%). Axial spondyloarthritis (axSpA)-like syndrome occurred in younger patients. Rh-irAEs were moderate or severe in 90%; 23.3% required hospitalization and 38.3% led to permanent ICI discontinuation. Systemic glucocorticoids (GCs) were used in 85.0%; 58.3% were GC-refractory and 53.3% required second-line immunomodulatory therapy. Complete remission was achieved in 33.3% and partial remission in 51.7%. Oncological progression occurred in 15.0% overall and in 28.1% of patients requiring second-line therapy. Male sex was the strongest predictor of second-line systemic therapy.

Rh-irAEs in a rheumatologists-referred population were more severe than previously described, with frequent ICI discontinuation and escalation beyond GCs. Male sex was associated with treatment escalation. An underrecognized axSpA-like phenotype occurred in younger patients, warranting further study.