• William J Sandborn, Subrata Ghosh, Julian Panes, Ivana Vranic, Wenjin Wang, Wojciech Niezychowski, and Study A3921043 Investigators.
• Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu.
• Clin. Gastroenterol. Hepatol. 2014 Sep 1; 12 (9): 1485-93.e2.

Background & AimsTofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through γ-chain-containing 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.MethodsPatients (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.ResultsA 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.ConclusionsThere 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.Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

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