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Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.
Gut. 2017 06; 66(6):1049-1059.Gut

Abstract

OBJECTIVE

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD).

DESIGN

We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study.

RESULTS

180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments.

CONCLUSIONS

Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib.

TRIAL REGISTRATION NUMBERS

NCT01393626 and NCT01393899.

Links

PMC Free PDF

Authors+Show Affiliations

Panés J
Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Sandborn WJ
Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Schreiber S
Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Sands BE
Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Vermeire S
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
D'Haens G
Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Panaccione R
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Higgins PDR
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Colombel JF
Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Feagan BG
Robarts Research Institute, London, Ontario, Canada.
Chan G
Pfizer Inc, Collegeville, Pennsylvania, USA.
Moscariello M
Pfizer Inc, Collegeville, Pennsylvania, USA.
Wang W
Pfizer Inc, Collegeville, Pennsylvania, USA.
Niezychowski W
Pfizer Inc, Collegeville, Pennsylvania, USA.
Marren A
Pfizer Inc, Collegeville, Pennsylvania, USA.
Healey P
Pfizer Inc, Groton, Connecticut, USA.
Maller E
Pfizer Inc, Collegeville, Pennsylvania, USA.

MeSH

AdultC-Reactive ProteinCrohn DiseaseDouble-Blind MethodFemaleHumansMaintenance ChemotherapyMaleMiddle AgedPiperidinesProtein Kinase InhibitorsPyrimidinesPyrrolesRemission InductionSeverity of Illness Index

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28209624

Clinical Trial Links

Clinical trial which this article describes [1]
Clinical trial which this article describes [2]
Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications

Citation

Panés, Julian, et al. "Tofacitinib for Induction and Maintenance Therapy of Crohn's Disease: Results of Two Phase IIb Randomised Placebo-controlled Trials." Gut, vol. 66, no. 6, 2017, pp. 1049-1059.
Panés J, Sandborn WJ, Schreiber S, et al. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017;66(6):1049-1059.
Panés, J., Sandborn, W. J., Schreiber, S., Sands, B. E., Vermeire, S., D'Haens, G., Panaccione, R., Higgins, P. D. R., Colombel, J. F., Feagan, B. G., Chan, G., Moscariello, M., Wang, W., Niezychowski, W., Marren, A., Healey, P., & Maller, E. (2017). Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut, 66(6), 1049-1059. https://doi.org/10.1136/gutjnl-2016-312735
Panés J, et al. Tofacitinib for Induction and Maintenance Therapy of Crohn's Disease: Results of Two Phase IIb Randomised Placebo-controlled Trials. Gut. 2017;66(6):1049-1059. PubMed PMID: 28209624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. AU - Panés,Julian, AU - Sandborn,William J, AU - Schreiber,Stefan, AU - Sands,Bruce E, AU - Vermeire,Séverine, AU - D'Haens,Geert, AU - Panaccione,Remo, AU - Higgins,Peter D R, AU - Colombel,Jean-Frederic, AU - Feagan,Brian G, AU - Chan,Gary, AU - Moscariello,Michele, AU - Wang,Wenjin, AU - Niezychowski,Wojciech, AU - Marren,Amy, AU - Healey,Paul, AU - Maller,Eric, Y1 - 2017/02/16/ PY - 2016/07/27/received PY - 2017/01/16/revised PY - 2017/01/17/accepted PY - 2017/2/18/pubmed PY - 2017/8/5/medline PY - 2017/2/18/entrez KW - CLINICAL TRIALS KW - CROHN'S DISEASE KW - IMMUNOLOGY SP - 1049 EP - 1059 JF - Gut JO - Gut VL - 66 IS - 6 N2 - OBJECTIVE: Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). DESIGN: We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. RESULTS: 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. CONCLUSIONS: Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. TRIAL REGISTRATION NUMBERS: NCT01393626 and NCT01393899. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/28209624/Tofacitinib_for_induction_and_maintenance_therapy_of_Crohn's_disease:_results_of_two_phase_IIb_randomised_placebo_controlled_trials_ DB - PRIME DP - Unbound Medicine ER -