Orofacial granulomatosis associated with Crohn's disease: clinical phenotype and response to biologics and Janus kinase inhibitor therapy in a large multi-center cohort.

BACKGROUND & AIMS: Orofacial granulomatosis (OFG) is strongly associated with Crohn's disease (CD). The CD phenotype associated with OFG is poorly defined, and there is little evidence regarding treatment. We aimed to characterize OFG-associated CD phenotypes and evaluate the response of OFG to advanced therapies in the largest cohort described to date. METHODS: We conducted a retrospective cohort study of patients with OFG and CD from two UK centers, derived from patient records compiled since 2008. Phenotypic characteristics were compared with a CD control cohort of 1609 individuals without OFG from the NIHR IBD-BioResource. Clinical response to biologic/Janus kinase inhibitor (JAKi) therapies was assessed. RESULTS: A total of 117 patients were included. Compared with controls, OFG was associated with earlier CD diagnosis (<17 years: 43% vs 22%, P < .001), increased ileocolonic disease (61% vs 41%, P < .001), perianal disease (46% vs 35%, P = .012), and upper gastrointestinal disease (21% vs 8%, P < .001). Clinical remission was achieved in 29 of 53 (55%) prescribed infliximab and 35 of 59 (59%) prescribed adalimumab, with frequent dose escalation. Remission was achieved with ustekinumab, risankizumab, and upadacitinib in 14 of 25 (56%), 6 of 12 (50%), and 3 of 5 (60%), respectively in biologic-experienced patients. Higher anti-TNF drug levels were associated with higher odds of achieving treatment response (adalimumab OR 1.14 per 1 µg/mL increase, P = .049; infliximab OR 1.27, P = .047). CONCLUSIONS: OFG is associated with a distinct CD phenotype characterized by frequent UGI and perianal involvement. Advanced therapies, including anti-TNF, anti-IL23, and JAKi therapies, are effective, with evidence supporting dose optimization.