Checkpoint Inhibitor-related Myositis – Something Different Save

As expected, this year’s ACR meeting saw an upswing in the number of abstracts on immune related adverse events from checkpoint inhibitor therapy compared to last year. With the increase in approved indications for checkpoint inhibitors (CPIs), rheumatologists everywhere are going to be getting referrals for rheumatic irAEs.

Two abstracts in particular caught my eye as they both shed some light on CPI-related myositis, a rare but often devastating complication.

Andrew Mammen presented results of a study (abstract #2288) in which they collected serum and PBMCs before and after avelumab (anti-PD-L1) therapy in patients with thymoma and monitored for CK elevations. They also assessed for thymoma- and myositis-associated autoantibodies. They enrolled 8 patients, all with normal baseline CK levels. Four patients developed elevated CK (762-16,037 IU/L) and proximal muscle weakness after avelumab initiation. These patients were treated with immunosuppressive therapy for myositis and all CK levels normalized within weeks. Of note, one patient with myositis also developed myocarditis. Very interestingly, all 4 patients who developed myositis had pre-existing anti-AChR autoantibodies, and none were positive for any traditional myositis autoantibody. While we are still learning the pathophysiologic mechanism of irAEs, this study suggests that some patients who develop myositis may have a predisposition to autoimmunity, and that we should be screening these patients pre-CPI.

A second abstract (#2976) looking at 180 CPI-related myositis cases collected from a WHO database (VigiBase) found that this entity carries a significant morbidity and mortality, with fatalities occurring 21.2%. They also found a proportion of patients have atypical features including concurrent myocarditis in 16.1% and myasthenia gravis-like symptoms in 15.6%.

We have much to learn about rheumatic irAEs, and the 20+ abstracts presented at this meeting reassure me we are headed in the right direction to answering key questions about risk factors, biomarkers, pathophysiology and treatment, as well as raising awareness among rheumatologists.