Journal Article

Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment

Coutte, Laetitia, Belkhir, Rakiba, Hollebecque, Antoine, Fain, Olivier, Marabelle, Aurélien, Dunogeant, Laetitia, Mouterde, Gaël, Pertuiset, Edouard, Lambotte, Olivier, Besse, Benjamin, Burel, Sébastien Le, Voisin, Anne-Laure, Leary, Alexandra, Pontoizeau, Clémence, Mariette, Xavier

2017

Overview

ObjectivesImmune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment.MethodsThis was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR.ResultsIn 10 patients who received ICI therapy (all anti-PD-1 or anti-PDL1 antibodies), RA or PMR developed at a median of 1 month (1 to 9) after exposure. No patient had pre-existing rheumatic or autoimmune disease. RA developed in six patients; all six were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and four for rheumatoid factor. Anti-CCP antibodies were detected in two out of three patients tested before immunotherapy. Disease-modifying antirheumatic drugs were needed for three patients; the three others received corticosteroids or non-steroid anti-inflammatory drugs. PMR was diagnosed in four patients, all responded to corticosteroids. Despite these IrAEs, immunotherapy was pursued for all but one patient until cancer progression.ConclusionsThis is the first description of RA occurring after ICI therapy for cancer. PMR can also occur after ICI, particularly after anti-PD-1 therapy. All cases responded to corticosteroids or with immunosuppressive therapy. Collaboration between rheumatologists and oncologists is crucial and could lead to better recognition and care of these patients.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Aged / Aged, 80 and over / Anti-inflammatory agents / Antibodies / Antibodies - blood / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal, Humanized - adverse effects / Antineoplastic Agents - adverse effects / Apoptosis / Arthralgia / Arthritis, Rheumatoid - blood / Arthritis, Rheumatoid - chemically induced / Arthritis, Rheumatoid - drug therapy / Autoimmune diseases / B7-H1 Antigen - antagonists & inhibitors / Bioengineering / Cancer / Cancer therapies / Cell death / Citrulline / Clinical and epidemiological research / Clinical trials / Collaboration / Corticosteroids / CTLA-4 Antigen - antagonists & inhibitors / Cytotoxicity / Disease / Female / Human health and pathology / Humans / Imaging / Immune checkpoint inhibitors / Immunoglobulins / Immunosuppressive agents / Immunotherapy / Inflammation / Internal medicine / Ipilimumab / Life Sciences / Ligands / Lung cancer / Lymphocytes T / Male / Melanoma / Mesothelioma / Metastasis / Middle Aged / Nivolumab / Patients / PD-1 protein / Peptides, Cyclic - immunology / Polymyalgia rheumatica / Polymyalgia Rheumatica - blood / Polymyalgia Rheumatica - chemically induced / Polymyalgia Rheumatica - drug therapy / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Proteins / Psoriasis / Retrospective Studies / Rheumatic diseases / Rheumatism / Rheumatoid arthritis / Rheumatoid factor / Rheumatology / Rhumatology and musculoskeletal system