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Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis
  1. Anne R Bass1,2,
  2. Noha Abdel-Wahab3,
  3. Pankti D Reid4,
  4. Jeffrey A Sparks5,
  5. Cassandra Calabrese6,
  6. Deanna P Jannat-Khah7,8,
  7. Nilasha Ghosh1,2,
  8. Divya Rajesh9,
  9. Carlos Andres Aude7,
  10. Lydia Gedmintas10,
  11. Lindsey MacFarlane10,
  12. Senada Arabelovic10,
  13. Adewunmi Falohun3,
  14. Komal Mushtaq11,
  15. Farah Al Haj12,
  16. Adi Diab13,
  17. Ami A Shah14,
  18. Clifton O Bingham15,
  19. Karmela Kim Chan1,2,
  20. Laura C Cappelli15
  1. 1 Rheumatology, Hospital for Special Surgery, New York, New York, USA
  2. 2 Medicine, Weill Cornell Medicine, New York, New York, USA
  3. 3 Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  4. 4 Rheumatology, University of Chicago Medical Center, Chicago, Illinois, USA
  5. 5 Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  6. 6 Rheumatic & Immunologic Disease, Cleveland Clinic, Cleveland, Ohio, USA
  7. 7 Jannat Khah: Medicine; Aude: Rheumatology, Hospital for Special Surgery, New York, New York, USA
  8. 8 Epidemiology in Medicine, Weill Cornell Medical College, New York, New York, USA
  9. 9 Harvard Medical School, Boston, Massachusetts, USA
  10. 10 Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  11. 11 Medicine, Cleveland Clinic, Cleveland, Ohio, USA
  12. 12 Hematology and Medical Oncology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA
  13. 13 Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  14. 14 Medicine/Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  15. 15 Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr Anne R Bass, Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA; bassa{at}hss.edu

Abstract

Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).

Methods The retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.

Results 147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.

Conclusion The treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.

  • methotrexate
  • arthritis
  • biological therapy
  • outcome assessment, health care
  • tumor necrosis factor inhibitors

Data availability statement

No data are available. All data relevant to the study are included in the article or uploaded as an online supplemental information.

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Data availability statement

No data are available. All data relevant to the study are included in the article or uploaded as an online supplemental information.

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Footnotes

  • Handling editor Josef S Smolen

  • Twitter @lovetolearn27, @ReidMDMPH, @jeffsparks, @CCalabreseDO, @CappelliMD

  • NA-W, PDR, JAS and CC contributed equally.

  • Contributors The following authors contributed to study design: ARB, NA-W, PDR, JAS, CC, DPJ-K, NG, KKC and LCC. All of the authors contributed to the data collection and critical revision of the manuscript. ARB served as guarantor of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests ARB: Rheumatology Research Foundation, Hospital for Special Surgery, Memorial Sloan Kettering Cancer Center. PDR: University of Chicago Institute of Translational Medicine K12/KL2 5KL2TR002387-05, University of Chicago COVID-19 Funds to Retain Clinical Scientists by the SECURED, Level Ex, pending patent for IL6 inhibitors for viral pneumonitis. NA-W: NIAID K01 A1163412, MD Anderson, ChemoCentryx. JAS: NIAMS R01 AR077607, P30 AR070253 and P30 AR072577, R. Bruce and Joan M. Mickey Research Scholar Fund, the Laura Gund Award for Rheumatoid Arthritis Research and Care, Rheumatology Research Foundation, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer. CC: Astrazenica, Sanofi, Lilly. DPJ-K: Walgreens Boots Alliance, AstraZeneca, Cytodyn. NG: Hospital for Special Surgery. AD: Nektar Therapeutics, Idera Pharmaceuticals, Apexigen. AAS: NIAMS K24 AR080217, RO1 AR073208, Arena Pharmaceuticals; Eicos Sciences, Kadmon Corporation Medpace LLC; Bingham: Bristol Myers Squibb, UptoDate. LCC: NIAMS K23 AR075872, Bristol-Myers Squibb. This work has been presented as an abstract at the American College of Rheumatology Convergence Meeting (November 2022) and to the Society for the Immunotherapy of Cancer Annual Meeting (November 2022).

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.