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Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer—clinical aspects and relationship with tumour response: a single-centre prospective cohort study
  1. Marie Kostine1,
  2. Léa Rouxel1,
  3. Thomas Barnetche1,
  4. Rémi Veillon2,
  5. Florent Martin2,
  6. Caroline Dutriaux3,
  7. Léa Dousset3,
  8. Anne Pham-Ledard3,
  9. Sorilla Prey3,
  10. Marie Beylot-Barry3,
  11. Amaury Daste4,
  12. Marine Gross-Goupil4,
  13. Julie Lallier4,
  14. Alain Ravaud4,
  15. Edouard Forcade5,
  16. Bernard Bannwarth1,
  17. Marie-Elise Truchetet1,
  18. Christophe Richez1,
  19. Nadia Mehsen1,
  20. Thierry Schaeverbeke1
  21. and on behalf of the FHU ACRONIM
  1. 1Rheumatology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France
  2. 2Pulmonology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France
  3. 3Dermatology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France
  4. 4Oncology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France
  5. 5Hematology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France
  1. Correspondence to Dr Marie Kostine, Rheumatology Department, Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux 33000, France; marie.kostine{at}chu-bordeaux.fr

Abstract

Objectives To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response.

Methods This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management.

Results From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001).

Conclusion Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.

  • arthritis
  • polymyalgia rheumatica
  • psoriatic arthritis
  • inflammation
  • treatment

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Footnotes

  • MK and LR contributed equally.

  • Handling editor Josef S Smolen

  • Contributors All the authors contributed to the manuscript: conception and design (LR, NM, MK and TS), collection of data (all authors) and statistical analysis (TB). MK, LR and TS drafted the manuscript, and all the authors critically reviewed and approved the final version of the manuscript.

  • Competing interests MB-B reports consulting and advisory boards for BMS and MSD France. AR reports being a member of Global, European and/or French Advisory Board in GU tumours and/or immunotherapy for Pfizer, Novartis, BMS, Roche, Astra Zeneca and MSD and received travel support from Pfizer, BMS, Roche, Astra Zeneca and MSD. SP reports consulting for BMS and travel support from MSD. AP-L has received honoraria and travel support from BMS and MSD. RV reports being one of the investigators for a clinical trial from BMS, consulting and advisory boards for BMS and MSD and travel support from BMS and MSD. All the others authors declared no conflict of interest for this work.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The study was approved by the local ethics committee (CE-GR-2017/007).

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

  • Data sharing statement We are publishing all data either in the paper or in the online supplementary material.

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