Upadacitinib’s Effectiveness for Perianal Fistulizing Crohn’s Disease

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J-F Colombel et al. Clinical Gastroenterology and Hepatology, Volume 23, Issue 6, 1019 – 1029. Open Access! Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials

Methods: This post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in the following studies: phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials. It was noted that there were 1021 patients in U-EXCEL and U-EXCEED; 143 (14.0%) had any fistulas at baseline (66 draining). Most (n = 128) had perianal fistulas (56 draining).

Key findings:

  • Fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo
These slides from Figure 1 show the resolution of drainage in perianal draining fistulas, closure of external perianal fistula openings, and closure of external openings for any fistula at week 12 of the induction trials and week 52 of the maintenance trial.

Discussion points:

  • Patients with draining fistulas often experience higher disease burden
  • Most patients in U-EXCEL and U-EXCEED had failed at least 2 prior biologic treatments (which often included anti-TNF therapy), reflecting a more refractory and difficult-to-treat population in CD
  • Despite the presence of perianal disease, patients with fistulizing CD treated with upadacitinib showed concurrent improvements in CD symptoms (CDAI, SF, and APS), luminal disease (endoscopic response and SES-CD), and markers of inflammation

My take: This study shows that upadacitinib is more effective than placebo; however, the majority of patients continued with ongoing perianal disease.

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