Beyond Glucocorticoids: The Current Landscape and Prospects for Treating Immune Checkpoint Inhibitor‐Induced Autoimmunity

The rapid integration of immune checkpoint inhibitors (ICIs) into standard oncology protocols has birthed a new frontier in clinical rheumatology: immune‐related adverse events (irAEs). By disrupting the programmed cell death‐1 (PD‐1)/PD‐L1 and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) axes to restore antitumor T cell activity, these therapies inadvertently breach peripheral tolerance. This results in a spectrum of de novo autoimmune and inflammatory syndromes that frequently mimic established rheumatic diseases, including inflammatory arthritis and myositis. Although ICIs have revolutionized survival outcomes, the resultant irAEs pose a significant clinical challenge, affecting nearly 50% of patients and often necessitating the expertise of rheumatologists for management. This manuscript explores the unique rheumatologic phenotype of ICI‐induced toxicities, emphasizing the urgent need for a shift from broad‐spectrum glucocorticoid use toward targeted, mechanism‐driven therapies that do not compromise the abscopal antitumor effect. We review the current landscape of clinical trials investigating the repurposing of traditional disease‐modifying antirheumatic drugs and advanced biologics. Specifically, we discuss the efficacy and safety of tumor necrosis factor–alpha inhibitors, interleukin‐6 receptor antagonists, and JAK inhibitors in the context of steroid‐refractory irAEs. We further analyze the molecular commonalities between idiopathic autoimmune diseases and ICI‐induced inflammation. As the patient population receiving ICIs grows, the rheumatologist's role as a co‐manager is increasingly essential. This review highlights the need for standardized grading and treatment algorithms for rheumatologic irAEs and advocates collaborative research to separate immunotherapy toxicities from its oncological benefits.