Immune Checkpoint–Induced Arthritis: A Comprehensive Single Cohort Descriptive Analysis from Clinical Evaluation to Histology

Laurent Meric de Bellefon¹Francesco Natalucci^1,2Adrien Nzesseu Toukap¹Tatiana Sokolova¹Christine Galant³Frank Aboubakar⁴Jean-François Baurain⁵Frank Cornelis⁶Ivan Borbath⁷Patrick Durez^1*

• ¹Pôle of systemic and inflammatory rheumatic pathologies, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium, Brussels, Belgium
• ²Cliniques Universitaires Saint-Luc, Woluwe-Saint-Lambert, Belgium
• ³Department of Pathological Anatomy, Cliniques Universitaires Saint-Luc, Brussels, Belgium, Brussels, Belgium
• ⁴Division of Pneumology, Cliniques Universitaires Saint-Luc, Brussels, Belgium, Brussels, Belgium
• ⁵Medical Oncology Department, Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium, Bruxelles, Belgium
• ⁶Medical Oncology Department, Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium
• ⁷Department of Hepato-gastroenterology, Cliniques Universitaires St Luc, Brussels, Belgium, Bruxelles, Belgium

Background/Purpose: Immune Checkpoint Inhibitors-induced arthritis (ICIs-IA) is the most common rheumatic immune-related adverse event (irAEs). Its pathogenesis remains unknown. 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 have analyzed the histology of ICI-induced arthritis. This study aimed to describe ICIs-IA from clinical presentation to histology. Materials and Methods: Patients who developed inflammatory arthritis while treated by ICIs have been enrolled. A US assessment of 38 joints (shoulders, elbows, knees, wrists, MCPs, PIPs, and MTPs) was systematically performed for inflammatory assessment and joint selection before synovial biopsy. Histopathological analyses consisted of a semiquantitave scores for histological parameters (synovial hyperplasia, fibrinoid necrosis, hypervascularization, inflammatory Infiltrate) and immunohistochemistry staining (CD3, CD20, CD138, and CD68). As a control group, we enrolled age and sex-matched untreated Early RA (ERA) patients with synovial tissue available. Results: Thirteen patients were included [M/F (10/3), median age 65 years (IQR14.5)]. Seven patients suffered from polyarthritis (53.8%), and five (38.4%) from oligoarthritis. The US pre-biopsy evaluation detected synovitis in 23.4% of joints; the most involved was the knee, followed by wrist, elbow, MCP2, MCP3, and MTP 2-5. Synovial tissue analysis was obtained mostly from the knee (69.2%). The histology of ICI-induced arthritis demonstrated a synovial inflammation similar to that found in ERA. ICIs-IA and ERA were similar from a clinical and histological perspective. Conclusions: Clinically, ICIs-IA manifested as oligo and polyarthritis, similar to RA. Synovial histology in ICI-induced arthritis is indistinguishable from RA, suggesting common pathogenic mechanisms. Further transcriptomics analyses are ongoing to better describe this new arthritis condition.