In patients with moderate-to-severe Crohn’s disease, the oral selective Janus kinase (JAK) inhibitor upadacitinib was superior to placebo when used for induction and maintenance treatment, researchers report.
Results of 2 induction trials and a maintenance trial are reported. Patients with moderate-to-severe Crohn’s disease were randomized to upadacitinib 45 mg or placebo once daily for 12 weeks in the induction trials (U-EXCEL and U-EXCEED). Those with a clinical response to upadacitinib induction therapy were randomized to 15 mg of upadacitinib 15 mg or 30 mg or to placebo once daily for 52 weeks in the U-ENDURE trial.
Based on clinical remission during induction (week 12) and maintenance (week 52), the study showed: “A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P <0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P <0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib.”
Editorial: “An understanding of the breadth of efficacy of upadacitinib on the full spectrum of Crohn’s disease will be important,” writes an editorialist. “Perianal fistulas are a distressing, often painful complication of Crohn’s disease, and polymorphisms in JAK1 have been associated with perianal fistulizing disease. A study of the use of upadacitinib in patients with perianal disease is warranted, as are studies of drugs to treat Crohn’s disease in Black and Hispanic persons, who were underrepresented in these and other trials. A timely assessment of safety in pregnancy and effects on fertility is also warranted; persons with [inflammatory bowel disease] are usually young and should not be unnecessarily denied access to JAK inhibitors.”