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OP021 Efficacy and safety of oral tofacitinib for induction therapy in patients with moderate-to-severe Crohns disease: results of a Phase 2b randomised placebo-controlled trial

J. Panés*1, W. J. Sandborn2, S. Schreiber3, B. E. Sands4, S. Vermeire5, G. Chan6, M. Moscariello6, W. Wang6, W. Niezychowski6, A. Marren6, P. Healey7, E. Maller6

1Hospital Clinicas de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, 2Division of Gastroenterology, University of California, San Diego, United States, 3Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany, 4Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, United States, 5Dept of Gastroenterology, University Hospitals Leuven, Leuven, Belgium, 6Pfizer Inc, Collegeville, United States, 7Pfizer Inc, Groton, United States

Background

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. Here we investigated the efficacy and safety of tofacitinib 5 mg and 10 mg twice daily (BID) for inducing clinical remission in patients with moderate-to-severe Crohn’s disease (CD).

Methods

We conducted a randomised, double-blind, placebo-controlled, multicentre Phase 2b study (NCT01393626). Adults with moderate-to-severe CD (CD activity index] ≥ 220 to ≤ 450, with intestinal ulcerations documented by colonoscopy within 6 weeks before randomisation), were randomised (1:1:1) to receive placebo or tofacitinib 5 mg or 10 mg BID for 8 weeks. Patients had a history of inadequate response or intolerance to ≥ 1 of corticosteroids, azathioprine/6-mercaptopurine, methotrexate, or tumour necrosis factor inhibitors (TNFi). Concomitant immunosuppressants were discontinued, and corticosteroids were allowed up to oral prednisone equivalent 30 mg/day or budesonide 9 mg/day. The primary endpoint was clinical remission (CDAI < 150) at week 8. Secondary endpoints included clinical response-70 and -100 (decrease in CDAI score from baseline > 70 and > 100, respectively) at weeks 2, 4, and 8; CDAI scores over time; and serum C-reactive protein (CRP) and faecal calprotectin (FCP) concentrations over time. Patients were assessed for safety through 4 weeks after last dose.

Results

In the study, 280 patients were randomised. The observed proportion of patients with clinical remission at week 8 was higher with tofacitinib 5 mg and 10 mg BID (43.5% and 43.0%, respectively) than placebo (36.7%). Similar findings were observed in TNFi-experienced patients with tofacitinib 10 mg BID. The observed proportions of response-100 (and response-70) at week 8 were 14%–16% (and 12%–14%) higher than placebo with tofacitinib 5 mg and 10 mg BID. Mean decreases from baseline in CDAI score and CRP concentration at week 8 were significantly larger with both tofacitinib doses compared with placebo. Serious infection developed in 2 patients in each treatment group. There was one case of malignancy (breast cancer; with 10 mg BID) and no death or herpes zoster cases. Tofacitinib was well tolerated.

Conclusion

After 8 weeks of induction therapy, small treatment effects in proportions of subjects in remission with tofacitinib 5 mg and 10 mg BID were observed. A consistent but modest treatment effect of tofacitinib was demonstrated by secondary clinical endpoints and supported by changes in biomarkers. Tofacitinib appears to be well tolerated.