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EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors
  1. Marie Kostine1,
  2. Axel Finckh2,
  3. Clifton O Bingham 3rd3,
  4. Karen Visser4,
  5. Jan Leipe5,6,
  6. Hendrik Schulze-Koops6,
  7. Ernest H Choy7,
  8. Karolina Benesova8,
  9. Timothy R D J Radstake9,
  10. Andrew P Cope10,
  11. Olivier Lambotte11,
  12. Jacques-Eric Gottenberg12,
  13. Yves Allenbach13,
  14. Marianne Visser14,
  15. Cindy Rusthoven14,
  16. Lone Thomasen15,
  17. Shahin Jamal16,
  18. Aurélien Marabelle17,
  19. James Larkin18,
  20. John B A G Haanen19,
  21. Leonard H Calabrese20,
  22. Xavier Mariette21,22,
  23. Thierry Schaeverbeke1
  1. 1 Rheumatology, University Hospital of Bordeaux, Bordeaux, France
  2. 2 Division of Rheumatology, University Hospital of Geneva, Geneva, Switzerland
  3. 3 Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA
  4. 4 Rheumatology, Haga Hospital, Den Haag, The Netherlands
  5. 5 Department of Medicine V, Division of Rheumatology, University Hospital Centre, Mannheim, Germany
  6. 6 Department of Internal Medicine IV, Division of Rheumatology and Clinical Immunology, University of Munich, Munich, Germany
  7. 7 Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
  8. 8 Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
  9. 9 Rheumatology and Clinical Immunology, Utrecht Medical Center, Utrecht, The Netherlands
  10. 10 Academic Department of Rheumatology, King's College London, London, UK
  11. 11 Internal Medicine and Clinical Immunology, Hopital Bicetre, Le Kremlin-Bicetre, France
  12. 12 Rheumatology, University Hospital of Strasbourg, Strasbourg, France
  13. 13 Internal Medicine and Clinical Immunology, Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France
  14. 14 EULAR PARE Patient Research Partners, Amsterdam, The Netherlands
  15. 15 Aarhus University Hospital, Aarhus, Denmark
  16. 16 Rheumatology, The University of British Columbia, Vancouver, British Columbia, Canada
  17. 17 Drug Development, Gustave Roussy Cancer Center, Villejuif, France
  18. 18 Royal Marsden Hospital NHS Foundation Trust, London, UK
  19. 19 The Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands
  20. 20 Immunology and Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA
  21. 21 Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud – Hôpital Bicêtre, Le Kremlin Bicêtre, France
  22. 22 3Université Paris-Sud, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin Bicêtre, France
  1. Correspondence to Dr Marie Kostine, Rheumatology, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux 33000, France; marie.kostine{at}


Background Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.

Methods First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.

Results The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.

Conclusion These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

  • treatment
  • arthritis
  • autoimmunity
  • inflammation
  • multidisciplinary team care

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  • XM and TS are joint senior authors.

  • Handling editor Josef S Smolen

  • Twitter @MarieKostine

  • Contributors The paper was drafted by MK, XM, AF and TS and all authors contributed with specific comments and revisions to the paper.

  • Funding This study was funded by European League Against Rheumatism (grant no: CLI106).

  • Competing interests MK: honoraria from Abbvie, BMS, Lilly, Novartis, Pfizer; TRDJR: grants from AbbVie, Takeda, UCB, Janssen, GSK and honoraria from Abbvie, Pfizer, Takeda, Lilly, Medimmune, Novartis, GSK, BMS, AstraZeneca, Janssen; XM: honoraria from BMS; COB: grants and honoraria from BMS and honoraria from Genetech/Roche, Sanofi/Regeneron; OL: grant from Gilead and honoraria from BMS, MSD, AstraZeneca, Janssen; JLe: grants from Novartis, Pfizer and honoraria from Abbvie, AstraZeneca, BMS, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; AM: grants from BMS, Merus and honoraria from Merck Serono, Lytix, BMS, Symphogen, Amgen, AZ/Medimmune, Servier, Gritstone, Pierre Fabre, EISAI, Sanofi; TS: honoraria from Pfizer, Lilly, Novartis, BMS, Abbvie, Sanofi; EHC: grants from Biogen, grants and honoraria from Amgen, Bio-Cancer, Roche, UCB, Pfizer, honoraria from Chugai Pharma, Abbvie, BMS, Celgene, Eli Lilly, Janssen, ObsEva, Regeneron, Sanofi, SynAct Pharma, Tonix, Gilead; LT: honoraria from Novartis; KB: grants from Abbvie, Novartis, Rheumaliga Baden-Württemberg and honoraria from MSD, Abbvie, BMS, Janssen, Lilly, Mundipharma, Novartis, Pfizer, Roche, UCB; KV: speaker fees from BMS; JLa: grants from Aveo and Pharmacyclics, grants and honoraria from Achilles Therapeutics, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche/Genetech and Immunocore, honoraria from AstraZeneca, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugen, Incyte, iOnctura, Kymab, Merck Serono, Secarna, Vitaccess and Covance; JBAGH: grants from BMS, Novartis and advisory boards and/or lectures for MSD, BMS, Roche, Novartis; J-EG: grants from BMS, UCB, Pfizer, Sanofi and honoraria from BMS, Lilly, Pfizer, Sanofi-Genzyme, UCB.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information

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