Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Understanding the pathophysiology of arthritis-irAE is critical to treating it without impeding antitumor immunity; however, these mechanisms remain elusive. As a first step in elucidating these mechanisms, we characterized functional immune cell profiles in synovial fluid from patients with arthritis-irAE.
Methods: We collected and performed immunoprofiling of synovial fluid from seven patients with active arthritis-irAE who received ICIs and three control patients with osteoarthritis who did not receive ICIs.
Results: Four patients developed arthritis after PD-1 inhibitor monotherapy and three after combination therapy with CTLA-4 and PD-1 inhibitors. Two patients in the combination therapy group required interleukin (IL)-6 receptor inhibitor therapy in addition to steroids, compared with one patient in the monotherapy group (sulfasalazine). IL-17-producing CD4+ T cells (Th17) were enriched in the combination therapy group (1.01±0.73% live CD4+ T cells in the monotherapy group compared with 3.19±0.31% in the combination therapy group; P=0.005). Synovial fluid levels of IL-6 and IL-17A, key cytokines for Th17 cell differentiation and function, were higher in the combination therapy group than in the monotherapy group, although this difference was not statistically significant.
Conclusion: Our results demonstrate that combination therapy with CTLA-4 and PD-1 inhibitors may result in enhanced incidence of steroid-resistant arthritis-irAE. Th17 cells were enriched in the synovial fluid of arthritis-irAE patients with combination therapy, suggesting their role in disease pathophysiology. Further studies with more cases and controls are needed to better understand the mechanisms underlying arthritis-irAE.
To cite this abstract in AMA style:Kim S, Tayar J, Suárez-Almazor M, Lu H, Zhao Y, Liu Z, Rodriguez E, Neelapu S, Wang J, Shah A, Tannir N, Gibbons D, Garcia-Manero G, Tawbi H, Hwu P, Futreal A, Diab A, Nurieva R. Enrichment of IL-17-producing CD4+ T Cells in Synovial Fluid from Patients with Arthritis After anti-CTLA-4 and anti-PD-1 Combination Therapy [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/enrichment-of-il-17-producing-cd4-t-cells-in-synovial-fluid-from-patients-with-arthritis-after-anti-ctla-4-and-anti-pd-1-combination-therapy/. Accessed November 23, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/enrichment-of-il-17-producing-cd4-t-cells-in-synovial-fluid-from-patients-with-arthritis-after-anti-ctla-4-and-anti-pd-1-combination-therapy/