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

Published:January 30, 2014DOI:

      Background & Aims

      Tofacitinib, 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.


      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.


      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.


      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. number: NCT00615199.


      Abbreviations used in this paper:

      AE (adverse event), ANC (absolute neutrophil count), CDAI (Crohn’s Disease Activity Index), CI (confidence interval), CRP (C-reactive protein), HDL (high-density lipoprotein), IBDQ (Inflammatory Bowel Disease Questionnaire), JAK (Janus kinase), LDL (low-density lipoprotein), SAE (serious adverse event), TNF (tumor necrosis factor)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Baumgart D.
        • Sandborn W.J.
        Crohn's disease.
        Lancet. 2012; 380: 1590-1605
        • Lichtenstein G.R.
        • Abreu M.T.
        • Cohen R.
        • et al.
        American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease.
        Gastroenterology. 2006; 130: 940-987
        • Karaman M.W.
        • Herrgard S.
        • Treiber D.K.
        • et al.
        A qualitive analysis of kinase inhibitor selectivity.
        Nat Biotechnol. 2008; 26: 127-132
        • Meyer D.M.
        • Jesson M.I.
        • Li X.
        • et al.
        Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis.
        J Inflamm. 2010; 7: 41
        • Fleischmann R.
        • Kremer J.
        • Cush J.
        • et al.
        Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.
        N Engl J Med. 2012; 367: 495-507
        • Papp K.
        • Menter A.
        • Strober B.
        • et al.
        Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebo-controlled dose-ranging study.
        Br J Dermatol. 2012; 167: 668-677
        • Sandborn W.J.
        • Ghosh S.
        • Panes J.
        • et al.
        Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.
        N Engl J Med. 2012; 367: 616-624
        • Vincenti F.
        • Tedesco S.H.
        • Busque S.
        • et al.
        Randomized phase 2b trial of tofacitinib (CP-690,550) in de novo kidney transplant patients: efficacy, renal function and safety at 1 year.
        Am J Transplant. 2012; 12: 2446-2456
        • Best W.R.
        • Becktel J.M.
        • Singleton J.W.
        • et al.
        Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.
        Gastroenterology. 1976; 70: 439-444
        • Irvine E.J.
        • Feagan B.
        • Rochon J.
        • et al.
        Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group.
        Gastroenterology. 1994; 106: 287-296
        • Su C.
        • Lichtenstein G.R.
        • Krok K.
        • et al.
        A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease.
        Gastroenterology. 2004; 126: 1257-1269
        • Targan S.R.
        • Hanauer S.B.
        • van Deventer S.J.
        • et al.
        A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.
        N Engl J Med. 1997; 337: 1029-1035
        • Hanauer S.B.
        • Sandborn W.J.
        • Rutgeerts P.
        • et al.
        Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.
        Gastroenterology. 2006; 130: 323-333
        • Sandborn W.J.
        • Feagan B.G.
        • Stoinov S.
        • et al.
        Certolizumab pegol for the treatment of Crohn's disease.
        N Engl J Med. 2007; 357: 228-238
        • Sandborn W.J.
        • Rutgeerts P.
        • Enns R.
        • et al.
        Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.
        Ann Intern Med. 2007; 146: 829-838
        • Sandborn W.J.
        • Schreiber S.
        • Feagan B.G.
        • et al.
        Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial.
        Clin Gastroenterol Hepatol. 2011; 9: 670-678