A Phase 2 Study of Tofacitinib, an Oral Janus Kinase Inhibitor, in Patients With Crohn’s Disease (original) (raw)

2014, Clinical Gastroenterology and Hepatology

BACKGROUND & AIMS: Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through g-chaincontaining cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn's disease. METHODS: Patients (N [ 139; age, ‡18 y) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg (n [ 36), 5 mg (n [ 34), or 15 mg (n [ 35) tofacitinib or placebo (n [ 34), twice daily for 4 weeks, at 48 centers in 12 countries. The primary end point was the proportion of clinical responders at week 4 (decrease from baseline in the Crohn's Disease Activity Index score of ‡70 points [Response-70]). Secondary end points included clinical remission (Crohn's Disease Activity Index score of <150 points) at week 4. RESULTS: A clinical response was observed in 36% (P [ .467), 58% (P [ .466), and 46% (P ‡ .999) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 47% of patients given placebo. Clinical remission was observed in 31% (P [ .417), 24% (P [ .776), and 14% (P [ .540) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 21% of patients given placebo. The 15-mg dose of tofacitinib reduced levels of C-reactive protein and fecal calprotectin from baseline. Adverse and serious adverse events were similar among groups. Dose-dependent increases in low-and high-density lipoprotein cholesterol were observed in patients given the 5-or 15-mg doses of tofacitinib. CONCLUSIONS: There were no significant differences in the percentage of patients with moderate-to-severe active Crohn's disease who achieved clinical responses (Response-70) or clinical remission after 4 weeks' administration of tofacitinib (1, 5, or 15 mg) or placebo twice daily. However, a large percentage of patients given placebo achieved Response-70 or remission. Reductions in C-reactive protein and fecal calprotectin levels among patients given the 15-mg dose of tofacitinib indicate its biologic activity. ClinicalTrials.gov number: NCT00615199.