Rheumatic diseases and treatment with checkpoint inhibitors
Authors:
Pavelka Karel
Authors‘ workplace:
Revmatologický ústav Praha
Published in:
Čes. Revmatol., 31, 2023, No. 2, p. 89-97.
Category:
Reviews
Overview
Pavelka K. Rheumatic diseases and treatment with checkpoint inhibitors
Tumor treatment with immune checkpoint inhibitors (ICIs) has improved the outcomes of oncological treatment on the one hand but can cause several immune-related adverse effects (AEs) on the other. ICIs are monoclonal antibodies that block CTLA-4, PD-1, and PD-L1, thereby increasing the activation of T-cells, which then have a greater ability to kill tumor cells, but can also trigger the onset or flare-up of an autoimmune disease. The most common immune-related side effects include skin rashes, colitis, thyroiditis, hepatitis, and also rheumatic diseases. Common rheumatic side effects of this treatment include polyarthritis (RA-like), polymyalgia rheumatica (PMR), and the myositis-myastheniamyocarditis triad. In an analysis of 372 patients with immune-related adverse effects of rheumatic origin, half of the patients had polyarthritis and a fifth of the patients had PMR. The incidence of autoantibodies in polyarthritis induced by ICIs is significantly lower than in primary RA (rheumatoid factor positivity in 9%, anticitrullinated antibody positivity in 8%). Patients with a pre-existing rheumatic disease before treatment with ICIs have an increased risk of developing immune-related side effects; on the other hand, they may have a better course of arthritis. Glucocorticoids are used in the treatment of RA induced by ICIs, but some patients require treatment with disease-modifying antirheumatic drugs (DMARDs). The drug of choice is methotrexate, followed by biological and targeted synthetic DMARDs. Of the biological DMARDs, there is some experience with the IL-6R inhibitor tocilizumab, which led to polyarthritis regression in 11/13 patients but also led to serious side effects (GIT perforation, cancer progression in half of the patients). Other studies show the suitability of using TNF-blockers. In case of more serious immune-related adverse effects, treatment with ICIs must be discontinued.
Keywords:
immune checkpoint inhibitors – tocilizumab – autoimmune-related side effects
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