Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

Abstract

Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs. Clinical challenge You receive a consult from a local oncologist. A 65-yearold man with a history of knee osteoarthritis (OA) who had previously undergone total joint arthroplasty of the left knee and is being treated with nivolumab (anti-programmed death 1 [anti-PD-1] monoclonal antibody) for non-small cell lung cancer has new symptoms of severe aching in his arms and legs, with limited mobility. The oncologist does not localize symptoms to the joints and/or muscles but notes that the patient is having trouble doing chores around the house such as cleaning and cooking.

Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events

“…RF and anti-citrullinated peptide antibodies (ACPA) are present in ≅19% of patients ( 51 , 180 , 182 ). Treatment of irAEs should be guided by severity ( 183 ). Most patients can be managed with non-steroidal anti-inflammatory drugs or intra-articular glucocorticoid injections.…”

“…Arthritis often persists even after stopping ICIs and may require prolonged immunosuppression with biological disease-modifying anti-rheumatic drugs (DMARDs) ( 40 ). Diagnostic and management algorithms for rheumatoid irAEs have been recently proposed ( 183 ).…”

“…ICI-related myositis can manifest in the form of acute or subacute myalgia or muscle weakness ( 183 , 184 ). When concomitant myocarditis and myasthenia gravis-like symptoms (e.g., ptosis and oculomotor weakness) occur, fatality rates are relatively high ( 185 ).…”

“…Glucocorticoids are the first-line therapy for ICI-associated myositis. Initial dosing can range from 0.5 mg/Kg prednisone daily up to 2,000 mg IV methylprednisolone ( 183 ). IVIG and plasmapheresis have been used in refractory cases ( 183 , 184 , 186 ).…”

Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR

“…The wide spectrum of irAE clinical presentations (eg, colitis, pancreatitis, hepatitis, myocarditis, neurotoxicities, thyroiditis, ICB-induced insulin dependent diabetes mellitus and lymphocytic hypophysitis) was discussed in detail during the meeting. As these clinical presentations have been thoroughly reviewed recently, [21][22][23][24][25][26][27][28] this report focuses on summarizing the critical challenges and opportunities posed by immunotherapy-induced irAEs and strategies that should be the focus of future investigations that were identified during the meeting.…”