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A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease.
Clin Gastroenterol Hepatol. 2014 Sep; 12(9):1485-93.e2.CG

Abstract

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.

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Sandborn WJ
Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu.
Ghosh S
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Panes J
Gastroenterology Department, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain.
Vranic I
Global Medicine Development, Pfizer Inc, Sandwich, United Kingdom.
Wang W
Global Innovative Pharma Division, Pfizer Inc, Collegeville, Pennsylvania.
Niezychowski W
Global Medicine Development, Pfizer Inc, Collegeville, Pennsylvania.
Study A3921043 Investigators
No affiliation info available

MeSH

AdultAnimalsBlood Chemical AnalysisC-Reactive ProteinCrohn DiseaseFecesFemaleHumansJanus KinasesLeukocyte L1 Antigen ComplexMaleMiddle AgedPiperidinesPlacebosProtein Kinase InhibitorsPyrimidinesPyrrolesTreatment Outcome

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

24480677

Clinical Trial Links

Clinical trial which this article describes

Citation

Sandborn, William J., et al. "A Phase 2 Study of Tofacitinib, an Oral Janus Kinase Inhibitor, in Patients With Crohn's Disease." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 12, no. 9, 2014, pp. 1485-93.e2.
Sandborn WJ, Ghosh S, Panes J, et al. A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2014;12(9):1485-93.e2.
Sandborn, W. J., Ghosh, S., Panes, J., Vranic, I., Wang, W., & Niezychowski, W. (2014). A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 12(9), 1485-e2. https://doi.org/10.1016/j.cgh.2014.01.029
Sandborn WJ, et al. A Phase 2 Study of Tofacitinib, an Oral Janus Kinase Inhibitor, in Patients With Crohn's Disease. Clin Gastroenterol Hepatol. 2014;12(9):1485-93.e2. PubMed PMID: 24480677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease. AU - Sandborn,William J, AU - Ghosh,Subrata, AU - Panes,Julian, AU - Vranic,Ivana, AU - Wang,Wenjin, AU - Niezychowski,Wojciech, AU - ,, Y1 - 2014/01/27/ PY - 2013/06/24/received PY - 2014/01/03/revised PY - 2014/01/16/accepted PY - 2014/2/1/entrez PY - 2014/2/1/pubmed PY - 2015/5/28/medline KW - CP-690,550 KW - Crohn’s Disease KW - Randomized Control Trial KW - Tofacitinib SP - 1485 EP - 93.e2 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin Gastroenterol Hepatol VL - 12 IS - 9 N2 - 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. 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. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/24480677/A_phase_2_study_of_tofacitinib_an_oral_Janus_kinase_inhibitor_in_patients_with_Crohn's_disease_ DB - PRIME DP - Unbound Medicine ER -