Effect of JAK inhibitors on extraintestinal manifestations and concurrent immune-mediated inflammatory diseases in patients with inflammatory bowel disease

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BACKGROUND AND AIMS: Extraintestinal manifestations (EIMs) and immune-mediated inflammatory diseases (IMIDs) are common in inflammatory bowel diseases (IBD) and contribute substantially to morbidity. The aim was to evaluate the real-world effectiveness of JAK inhibitors on EIMs/IMIDs. METHODS: This multicenter retrospective study included adults with ulcerative colitis (UC) or Crohn's disease (CD) and one or more EIM/IMID initiating a JAK inhibitor (tofacitinib, upadacitinib, or filgotinib). Baseline was defined as treatment initiation; EIM/IMID and IBD activity were assessed at fixed timepoints using physician global assessment. Response rates are reported as observed, with patients discontinuing for worsening of the manifestation counted as non-responders. Logistic and Cox regression analyses identified factors associated with response and treatment discontinuation. RESULTS: A total of 246 patients were included; 67% had two or more prior advanced therapies. Peripheral spondyloarthritis (SpA) (48%) and axial SpA (43%) were the most prevalent EIMs/IMIDs. Peripheral SpA response rates were 82% post-induction and 74% at month 12; axial SpA response rates were 71% and 59%, respectively. Psoriasis response was observed in 65% post-induction and in 50% at month 12, and hidradenitis suppurativa response in 91% and 78%, respectively. Steroid-free clinical IBD remission was 58% at month 12, and was independently associated with peripheral SpA response (adjusted odds ratio [aOR] 4.2, 95% CI 1.2-14.7). Treatment was discontinued in 31%; factors associated with discontinuation were filgotinib use (adjusted hazard ratio [aHR] 3.0, 95% CI 1.4-6.2) and co-existing axial and peripheral SpA (aHR 2.8, 95% CI 1.5-5.1). CONCLUSIONS: JAK inhibitors were associated with favorable physician-assessed outcomes for EIMs/IMIDs in treatment-experienced IBD patients. Co-existing axial and peripheral SpA was associated with treatment discontinuation, suggesting a more complex phenotype.

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