Abstract Background Perianal Crohn’s disease (pCD) is difficult to treat. Although anti-TNF agents are the mainstay of medical therapy, many patients become refractory or intolerant. Upadacitinib (UPA) has shown efficacy for luminal CD in phase 3 trials and post hoc analyses have suggested benefit in pCD. This study aims to assess the effectiveness of UPA in refractory pCD in the real-world clinical practice. Methods Retrospective cohort study including patients with active pCD treated with UPA in our IBD Unit between September 2023 and October 2025. Demographic and disease characteristics, prior perianal surgery, and exposure to immunomodulators or biologics were recorded. Treatment success was defined as: clinical response/remission (CR) (improvement or absence of spontaneous drainage), biological response (BR) (reduction in CRP and faecal calprotectin), MRI-based improvement or healing, and absence of new antibiotic or surgical interventions for pCD. Results Thirty-two patients were included (62,5% male; median age at diagnosis was 24 years(17-32); age at Upadacitinib initiation 36 years). Ileocolonic disease (46,9%) and 62% had previous perianal surgery. All had prior biologic exposure, with 59,4% receiving 2 advanced therapies. UPA 45mg maintenance after the standard 12-week induction period was used in 28 (87,5%) . CR at induction and at 6 and 12 months were comparable between patients receiving 45mg and those maintained on 30mg (p 0,05). At 3 months, CR was acieved 25/32 (78,1%); at 6 months (n = 28), CR to 24/28 (85,7%) and. At 12 months (n = 17), 82,4% maintained CR. Antibiotic or surgical interventions were required in 6 patients respectively (18,8%). Treatment persistence was 79% at 6 months and 67% at 12 months (median follow-up 11 months). Adverse events included acne (15,6%) and infections (18,8%), with no thrombotic events or discontinuations. Conclusion In this real-world single-centre cohort of highly refractory pCD, UPA achieved high and sustained CR and an acceptable safety profile. These findings support upadacitinib as a promising therapeutic option for complex pCD and highlight the need for prospective studies to define optimal dosing, duration, and radiological endpoints. Conflict of interest: Mrs. Algara, Maria: No conflict of interest Suárez-Saro Fernández, Ana: No conflict of interest Ferreiro Pérez, Elena: No conflict of interest Franchez Martincorena, Beatriz: No conflict of interest Blanco, Alejandro: No conflict of interest Rafael De La Cruz Esteban, David: No conflict of interest López Romero-Salazar, Francisco: No conflict of interest Yela San Bernardino, M. Carmen: No conflict of interest Masedo Gonzalez, Angeles: No conflict of interest Casis Herce, M. Begoña: No conflict of interest Gonzalez Lama, Yago: I have provided scientific advisory / participated in educational activities / received unrestricted research grants / received payments for lecturing from Janssen, Takeda, Pfizer, AbbVie, Lilly, Alfasigma, Ferring, Gilead, Amgen.
Algara et al. (2026) studied this question.