Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II)

Silvio Danese, Séverine Vermeire, Paul Hellstern, Remo Panaccione, Gerhard Rogler, Gerald Fraser, Anna Kohn, Pierre Desreumaux, Rupert W Leong, Gail M Comer, Fabio Cataldi, Anindita Banerjee, Mary K Maguire, Cheryl Li, Natalie Rath, Jean Beebe, Stefan Schreiber

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Abstract

OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.

DESIGN: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included.Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28.OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up.

RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis.

CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development.

TRIAL REGISTRATION NUMBER: NCT01287897 and NCT01345318.

Original languageEnglish
JournalGut
DOIs
Publication statusE-pub ahead of print - Dec 15 2017

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Crohn Disease
Interleukin-6
Antibodies
Placebos
Nasopharyngitis
Therapeutics
Tumor Necrosis Factor-alpha
Subcutaneous Injections
Abscess
Abdominal Pain
Safety

Keywords

  • Journal Article

Cite this

Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II). / Danese, Silvio; Vermeire, Séverine; Hellstern, Paul; Panaccione, Remo; Rogler, Gerhard; Fraser, Gerald; Kohn, Anna; Desreumaux, Pierre; Leong, Rupert W; Comer, Gail M; Cataldi, Fabio; Banerjee, Anindita; Maguire, Mary K; Li, Cheryl; Rath, Natalie; Beebe, Jean; Schreiber, Stefan.

In: Gut, 15.12.2017.

Research output: Contribution to journalArticle

Danese, S, Vermeire, S, Hellstern, P, Panaccione, R, Rogler, G, Fraser, G, Kohn, A, Desreumaux, P, Leong, RW, Comer, GM, Cataldi, F, Banerjee, A, Maguire, MK, Li, C, Rath, N, Beebe, J & Schreiber, S 2017, 'Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II)', Gut. https://doi.org/10.1136/gutjnl-2017-314562
Danese, Silvio ; Vermeire, Séverine ; Hellstern, Paul ; Panaccione, Remo ; Rogler, Gerhard ; Fraser, Gerald ; Kohn, Anna ; Desreumaux, Pierre ; Leong, Rupert W ; Comer, Gail M ; Cataldi, Fabio ; Banerjee, Anindita ; Maguire, Mary K ; Li, Cheryl ; Rath, Natalie ; Beebe, Jean ; Schreiber, Stefan. / Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II). In: Gut. 2017.
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T1 - Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II)

AU - Danese, Silvio

AU - Vermeire, Séverine

AU - Hellstern, Paul

AU - Panaccione, Remo

AU - Rogler, Gerhard

AU - Fraser, Gerald

AU - Kohn, Anna

AU - Desreumaux, Pierre

AU - Leong, Rupert W

AU - Comer, Gail M

AU - Cataldi, Fabio

AU - Banerjee, Anindita

AU - Maguire, Mary K

AU - Li, Cheryl

AU - Rath, Natalie

AU - Beebe, Jean

AU - Schreiber, Stefan

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2017/12/15

Y1 - 2017/12/15

N2 - OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.DESIGN: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included.Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28.OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up.RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis.CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development.TRIAL REGISTRATION NUMBER: NCT01287897 and NCT01345318.

AB - OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.DESIGN: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included.Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28.OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up.RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis.CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development.TRIAL REGISTRATION NUMBER: NCT01287897 and NCT01345318.

KW - Journal Article

U2 - 10.1136/gutjnl-2017-314562

DO - 10.1136/gutjnl-2017-314562

M3 - Article

C2 - 29247068

JO - Gut

JF - Gut

SN - 0017-5749

ER -