Background/Purpose: The increasing use of Immune Check-Point Inhibitors (ICIs) to treat malignancy focused attention on immune-related adverse events (irAEs). ICIs-induced arthritis is the most common rheumatic irAEs. Its prevalence is usually underestimated, and the pathogenesis remains unknown (1). Ultrasound (US) Guided Synovial Biopsy (USGSB) has been proven a safe and reliable procedure in Rheumatoid Arthritis (RA), enlarging the understanding of synovitis in RA. To our knowledge, no studies analyzed the histology of ICIs-induced arthritis. This study aimed to describe ICIs-induced arthritis comprehensively, from the clinical presentation to the histological assessment, comparing the results with the clinical and histological characteristics of an Early RA (ERA) Cohort.

Methods: Oncological patients in treatment with ICIs have been enrolled.  Patients were referred to our attention by their oncologist to the appearance of signs and/or symptoms suggestive of arthritis. Each patient received a complete rheumatological evaluation including joint counts and research of autoantibodies (ANA, RF, and ACPA antibodies). An ultrasound-guided synovial biopsy of a small joint or a knee mini arthroscopy was performed. Synovial samples were analyzed for histology (Synovial Hyperplasia, Fibrinoid Necrosis, Hypervascularization, Inflammatory Infiltrate) and IHC (CD3, CD20, CD138, and CD68) on a semiquantitative 0-3 scale. US was systematically performed including scanning of 38 joints (shoulder, elbow, knee, wrist, MCP, IFP, and MTP joints). Synovitis was defined according to the OMERACT guidelines definition (2). As a control, we enrolled age and sex-matched untreated ERA patients.

Results: Up to now, thirteen patients were included [M/F (10/3), median age 65 years (IQR14.5)]. The clinical, serological, and demographic characteristics are reported in Table 1 including the compared ERA cohort. Six patients (46.1%) were positive for ANA or RF. One patient suffered from monoarthritis, 5 (38.4%) from oligoarthritis, and the remaining 7 (53.8%) from polyarthritis. The systematic US pre-biopsy evaluation (Figure 1) demonstrated the presence of any grade synovitis in 23.4% of analyzed joints; the most commonly involved was the knee, followed by wrist, elbow, MCP2, MCP3, and MTP 2-5. The knee was by far the most biopsied joint (69.2%). The histology of ICIs-induced arthritis demonstrated high-grade synovitis: we did not identify any significant difference for any variable. Histology and IHC results did not correlate with the baseline disease severity (DAS28, TJC, SJC, CRP).

Conclusion: In our cohort, as in previous studies ICIs induced arthritis manifested as an oligo-polyarthritis, clinically similar to RA; small and large joints were similarly involved. Histology is not specific to ICI-induced arthritis and to date does not have a diagnostic value. However, the resemblance to ERA suggests common pathogenic mechanisms.  Considering the low numerosity of the cohort, we did not identify any correlation between disease activity and histological assessment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-checkpoint-induced-arthritis-a-comprehensive-single-cohort-descriptive-analysis-from-clinical-evaluation-to-histology/