Monday, 26 Aug 2019

You are here

Checkpoint Inhibitor-related Myositis – Something Different

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.


Add new comment

More Like This

With Autoimmunity, Checkpoint Inhibitors Can Be Used

Among patients with pre-existing autoimmune diseases who developed cancer and were treated with immune checkpoint inhibitors (ICI), flares of the underlying disease and other immune-related adverse events were common, a retrospective study conducted in France showed.

New EULAR/ACR Classification Criteria for SLE

The European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) have jointly developed new classification criteria for systemic lupus erythematosus (SLE); prompted by the need for criteria that were both highly sensitive and specific. The net result is improved sensitivity and specificity, but the use of positive ANA requirement along with a longer list of weighted criteria ensures its utility in SLE research (including early or latent SLE), but not clinical practice.

Sjogren's Syndrome at Risk for Psychiatric Disorders

A population-based claims study from Taiwan shows significantly increased incidences of depressive disorder, anxiety disorder, and sleep disorder in patients with primary Sjögren’s syndrome (pSS). 

Abatacept Disappoints in Systemic Sclerosis

A 12‐month, Phase 2 trial has shown that subcutaneous abatacept was well tolerated in patients with diffuse cutaneous systemic sclerosis (dcSSc), but failed to significantly change the skin outcomes as measured by the change in modified Rodnan skin score (mRSS)

FDA AAC Splits Vote in Favor of Nintedanib for Scleroderma Interstitial Lung Disease

The FDA convened Arthritis Advisory Committee to consider nintedanib for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) and voted 10-7 in favor of approving the drug for this new indication.