Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis

Ann Rheum Dis. 2023 Jul;82(7):920-926. doi: 10.1136/ard-2023-223885. Epub 2023 Apr 5.

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.

Keywords: arthritis; biological therapy; methotrexate; outcome assessment, health care; tumor necrosis factor inhibitors.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Biological Products* / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immune Checkpoint Inhibitors
  • Interleukin-6 Inhibitors
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Tumor Necrosis Factor-alpha

Substances

  • Antirheumatic Agents
  • Biological Products
  • Immune Checkpoint Inhibitors
  • Interleukin-6 Inhibitors
  • Methotrexate
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha