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Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment
  1. Rakiba Belkhir1,
  2. Sébastien Le Burel2,
  3. Laetitia Dunogeant3,
  4. Aurélien Marabelle4,
  5. Antoine Hollebecque4,
  6. Benjamin Besse5,
  7. Alexandra Leary5,
  8. Anne-Laure Voisin6,
  9. Clémence Pontoizeau7,
  10. Laetitia Coutte8,
  11. Edouard Pertuiset9,
  12. Gaël Mouterde10,
  13. Olivier Fain11,
  14. Olivier Lambotte2,12,
  15. Xavier Mariette1,13
  1. 1Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France
  2. 2AP-HP, Hôpital Bicêtre, Service de Médecine Interne et Immunologie clinique, Le Kremlin-Bicêtre, France
  3. 3Service de rhumatologie et médecine interne, Centre Hospitalier du Pays d’Aix, Aix-en-Provence, France
  4. 4Département d’Innovation Thérapeutique et Essais Précoces (DITEP), Gustave Roussy Cancer Campus, France
  5. 5Gustave Roussy Cancer Campus, Villejuif; Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France
  6. 6Institut Gustave Roussy, Unité Fonctionnelle de Pharmacovigilance, Villejuif, France
  7. 7Service de médecine nucléaire, Centre Hospitalier de Saint Brieuc, 22000 Saint Brieuc, France
  8. 8AP-HP, université Paris-Descartes, hôpital Cochin, centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, Paris, France
  9. 9Rheumatology Department, René Dubos Hospital, Pontoise, France
  10. 10Rheumatology Department, Lapeyronie Hospital and &EA 2415, Montpellier, France
  11. 11AP-HP, Service de Médecine Interne, Hôpital Saint-Antoine, Université Paris, France
  12. 12CEA, DSV/iMETI, Division d’Immunovirologie, IDMIT, Fontenay-aux-Roses, France
  13. 13Université Paris Sud, INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France
  1. Correspondence to Dr Xavier Mariette, Rheumatology, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 LeKremlin Bicêtre, France; xavier.mariette{at}bct.aphp.fr

Abstract

Objectives Immune 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.

Methods This 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.

Results In 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.

Conclusions This 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.

  • immune-checkpoint inhibitors
  • rheumatoid arthritis
  • polymyalgia rheumatica

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Footnotes

  • Contributors All the authors contributed to the manuscript: conception and design (RB and XM), collection of data (all authors). All the authors read and validated the final version of the manuscript.

  • Funding The authors received no financial support for the research, authorship and/or publication of this article.

  • Competing interests AM reports being one of the principal investigator for clinical trials from Roche/Genentech, BMS, Merck (MSD), Pfizer, Lytix pharma, Eisai, Astra Zeneca/Medimmune, Bayer, Celgene. AH reports advisory boards for Amgen and Lilly. OL reports consulting for MSD, BMS and Genzyme and received travel support from LFB and CSL Behring. All the others authors declared no conflict of interest for this work.

  • Patient consent Informed consent was obtained from all subjects, and the study was approved by the local ethics committee.

  • Ethics approval local ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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