Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

Stephen Hanauer; Remo Panaccione; Silvio Danese; Adam Cheifetz; Walter Reinisch; Peter D.R. Higgins; Deborah A. Woodworth; Haiying Zhang; Gary S. Friedman; Nervin Lawendy; Daniel Quirk; Chudy I. Nduaka; Chinyu Su

doi:10.1016/j.cgh.2018.07.009

Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

Stephen Hanauer^*, Remo Panaccione, Silvio Danese, Adam Cheifetz, Walter Reinisch, Peter D.R. Higgins, Deborah A. Woodworth, Haiying Zhang, Gary S. Friedman, Nervin Lawendy, Daniel Quirk, Chudy I. Nduaka, Chinyu Su

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

109 Scopus citations

Abstract

Background & Aims: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2). Methods: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein. Results: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups. Conclusions: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951.

Original language	English (US)
Pages (from-to)	139-147
Number of pages	9
Journal	Clinical Gastroenterology and Hepatology
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.cgh.2018.07.009
State	Published - Jan 2019

Keywords

Efficacy
IBD
Inflammatory Bowel Disease
Onset of Action

ASJC Scopus subject areas

Gastroenterology
Hepatology

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10.1016/j.cgh.2018.07.009

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Hanauer, S., Panaccione, R., Danese, S., Cheifetz, A., Reinisch, W., Higgins, P. D. R., Woodworth, D. A., Zhang, H., Friedman, G. S., Lawendy, N., Quirk, D., Nduaka, C. I., & Su, C. (2019). Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis. Clinical Gastroenterology and Hepatology, 17(1), 139-147. https://doi.org/10.1016/j.cgh.2018.07.009

@article{90918cebfa4443a4b3bc6b79ee3694bf,

title = "Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis",

abstract = "Background & Aims: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2). Methods: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein. Results: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups. Conclusions: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951.",

keywords = "Efficacy, IBD, Inflammatory Bowel Disease, Onset of Action",

author = "Stephen Hanauer and Remo Panaccione and Silvio Danese and Adam Cheifetz and Walter Reinisch and Higgins, {Peter D.R.} and Woodworth, {Deborah A.} and Haiying Zhang and Friedman, {Gary S.} and Nervin Lawendy and Daniel Quirk and Nduaka, {Chudy I.} and Chinyu Su",

note = "Funding Information: Conflicts of interest These authors disclose the following: Stephen Hanauer received consulting and lecture fees from AbbVie, Janssen, Samsung Bioepis, Takeda, and UCB; and has received consulting fees from Amgen, Aptalis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Hospira, Merck, Pfizer Inc, Salix and Shire. Remo Panaccione has received consulting fees from AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Biogen, Bristol-Myers Squibb, Celgene, Centocor, Cubist, Eisai, Elan, Ferring, Gilead, GlaxoSmithKline, Janssen, Merck, Pfizer, Robarts Clinical Trials, Salix, Samsung Bioepis, Shire, Takeda, and UCB; received research grants from AbbVie, Ferring, Janssen, and Takeda; received lectures and/or speaker bureau fees from AbbVie, Aptalis, AstraZeneca, Ferring, Janssen, Merck, Prometheus, Shire, and Takeda; and received advisory board fees from AbbVie, Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Celgene, Cubist, Eisai, Elan, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Salix, Schering-Plough, Shire, Takeda, and UCB. Silvio Danese has been a speaker, consultant, and an advisory board member for AstraZeneca, Boehringer Ingelheim, Cosmo Pharmaceuticals, Ferring, Genentech, Gr{\"u}nenthal, Johnson & Johnson, Merck & Co, Millennium, Novo Nordisk, Pfizer, Pharmacosmos, Takeda, TiGenix, and Vifor. Adam Cheifetz has been on consulting/advisory boards for AbbVie, AMAG, Ferring, Janssen, Miraca Laboratories, Pfizer Inc, and Takeda. Walter Reinisch has received grant support from Abbott Laboratories, AbbVie, AESCA, Centocor, Falk Pharma GmbH, Immundiagnostik, and MSD; consultancy fees from Abbott Laboratories, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Bioclinica, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, ChemoCentryx, Celgene, Celltrion, Centocor, Covance, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Gr{\"u}nenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestl{\'e}, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus, Robarts Clinical Trials, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB Pharma, Vifor, Zyngenia, and 4SC; speaker fees from Abbott Laboratories, AbbVie, AESCA, Aptalis, Celltrion, Centocor, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; and has been an advisory board member for Abbott Laboratories, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, ChemoCentryx, Celgene, Celltrion, Centocor, Danone Austria, Elan, Ferring, Galapagos, Genentech, Gr{\"u}nenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestl{\'e}, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB Pharma, Zyngenia, and 4SC. Peter D.R. Higgins has received consulting fees from AbbVie, Amgen, Genentech, JBR Pharma, and Lycera. Deborah A. Woodworth, Haiying Zhang, Gary S. Friedman, Nervin Lawendy, Daniel Quirk, Chudy I. Nduaka, and Chinyu Su are employees and stockholders of Pfizer Inc. Funding Information: Medical writing support, under the direction of the authors, was provided by Daniel Binks, PhD, of CMC CONNECT, a division of Complete Medical Communications Ltd, Macclesfield, UK, and was funded by Pfizer Inc, New York, NY, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). Publisher Copyright: {\textcopyright} 2019 AGA Institute",

year = "2019",

month = jan,

doi = "10.1016/j.cgh.2018.07.009",

language = "English (US)",

volume = "17",

pages = "139--147",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "1",

}

Hanauer, S, Panaccione, R, Danese, S, Cheifetz, A, Reinisch, W, Higgins, PDR, Woodworth, DA, Zhang, H, Friedman, GS, Lawendy, N, Quirk, D, Nduaka, CI & Su, C 2019, 'Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis', Clinical Gastroenterology and Hepatology, vol. 17, no. 1, pp. 139-147. https://doi.org/10.1016/j.cgh.2018.07.009

TY - JOUR

T1 - Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

AU - Hanauer, Stephen

AU - Panaccione, Remo

AU - Danese, Silvio

AU - Cheifetz, Adam

AU - Reinisch, Walter

AU - Higgins, Peter D.R.

AU - Woodworth, Deborah A.

AU - Zhang, Haiying

AU - Friedman, Gary S.

AU - Lawendy, Nervin

AU - Quirk, Daniel

AU - Nduaka, Chudy I.

AU - Su, Chinyu

N1 - Funding Information: Conflicts of interest These authors disclose the following: Stephen Hanauer received consulting and lecture fees from AbbVie, Janssen, Samsung Bioepis, Takeda, and UCB; and has received consulting fees from Amgen, Aptalis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Hospira, Merck, Pfizer Inc, Salix and Shire. Remo Panaccione has received consulting fees from AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Biogen, Bristol-Myers Squibb, Celgene, Centocor, Cubist, Eisai, Elan, Ferring, Gilead, GlaxoSmithKline, Janssen, Merck, Pfizer, Robarts Clinical Trials, Salix, Samsung Bioepis, Shire, Takeda, and UCB; received research grants from AbbVie, Ferring, Janssen, and Takeda; received lectures and/or speaker bureau fees from AbbVie, Aptalis, AstraZeneca, Ferring, Janssen, Merck, Prometheus, Shire, and Takeda; and received advisory board fees from AbbVie, Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Celgene, Cubist, Eisai, Elan, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Salix, Schering-Plough, Shire, Takeda, and UCB. Silvio Danese has been a speaker, consultant, and an advisory board member for AstraZeneca, Boehringer Ingelheim, Cosmo Pharmaceuticals, Ferring, Genentech, Grünenthal, Johnson & Johnson, Merck & Co, Millennium, Novo Nordisk, Pfizer, Pharmacosmos, Takeda, TiGenix, and Vifor. Adam Cheifetz has been on consulting/advisory boards for AbbVie, AMAG, Ferring, Janssen, Miraca Laboratories, Pfizer Inc, and Takeda. Walter Reinisch has received grant support from Abbott Laboratories, AbbVie, AESCA, Centocor, Falk Pharma GmbH, Immundiagnostik, and MSD; consultancy fees from Abbott Laboratories, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Bioclinica, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, ChemoCentryx, Celgene, Celltrion, Centocor, Covance, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestlé, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus, Robarts Clinical Trials, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB Pharma, Vifor, Zyngenia, and 4SC; speaker fees from Abbott Laboratories, AbbVie, AESCA, Aptalis, Celltrion, Centocor, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; and has been an advisory board member for Abbott Laboratories, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, ChemoCentryx, Celgene, Celltrion, Centocor, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestlé, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB Pharma, Zyngenia, and 4SC. Peter D.R. Higgins has received consulting fees from AbbVie, Amgen, Genentech, JBR Pharma, and Lycera. Deborah A. Woodworth, Haiying Zhang, Gary S. Friedman, Nervin Lawendy, Daniel Quirk, Chudy I. Nduaka, and Chinyu Su are employees and stockholders of Pfizer Inc. Funding Information: Medical writing support, under the direction of the authors, was provided by Daniel Binks, PhD, of CMC CONNECT, a division of Complete Medical Communications Ltd, Macclesfield, UK, and was funded by Pfizer Inc, New York, NY, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). Publisher Copyright: © 2019 AGA Institute

PY - 2019/1

Y1 - 2019/1

N2 - Background & Aims: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2). Methods: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein. Results: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups. Conclusions: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951.

AB - Background & Aims: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2). Methods: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein. Results: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups. Conclusions: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951.

KW - Efficacy

KW - IBD

KW - Inflammatory Bowel Disease

KW - Onset of Action

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U2 - 10.1016/j.cgh.2018.07.009

DO - 10.1016/j.cgh.2018.07.009

M3 - Article

C2 - 30012431

AN - SCOPUS:85057839542

SN - 1542-3565

VL - 17

SP - 139

EP - 147

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 1

ER -

Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

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