Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Jan;68(1):40-48.
doi: 10.1136/gutjnl-2017-314562. Epub 2017 Dec 15.

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

Silvio Danese #  1 , Séverine Vermeire  2 , Paul Hellstern  3 , Remo Panaccione  4 , Gerhard Rogler  5 , Gerald Fraser  6 , Anna Kohn  7 , Pierre Desreumaux  8 , Rupert W Leong  9 , Gail M Comer  10 , Fabio Cataldi  10 , Anindita Banerjee  11 , Mary K Maguire  12 , Cheryl Li  11 , Natalie Rath  12 , Jean Beebe  11 , Stefan Schreiber #  13
Affiliations
Clinical Trial

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

Silvio Danese et al. Gut. 2019 Jan.

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.

Keywords: anti-IL6 antibody; anti-TNF; crohn’s disease; inadequate response.

PubMed Disclaimer

Conflict of interest statement

Competing interests: SD is a speaker, consultant and advisory board member for Abbott Laboratories, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Hospira, Johnson and Johnson, Merck & Co, Millennium Takeda, Mundipharma, Novo Nordisk, Nycomed, Pharmacosmos, Pfizer, Schering-Plough, UCB Pharma and Vifor. SV received research support from AbbVie, MSD and Takeda and received consultancy and/or speaker honoraria from AbbVie, Celgene, Centocor, Ferring, Galapagos, Genentech/Roche, Hospira, MSD, Mundipharma, Pfizer, Shire and Takeda. PH is a consultant and/or advisory board participant for, and/or has received speaker honoraria, research support and/or educational grants from, Cubist, Evoke, Ferring, Forest, Furiex, Gilead, GlaxoSmithKline, Intercept, Ironwood, Menarini, Nature Coast Clinical Research, Pfizer, Rhythm, Salix, Synergy, Takeda, Theravance and Vivus. RP is a consultant for and/or received lecture fees from Abbott, AbbVie, Allergan, Amgen, AstraZeneca, Axcan Pharma, Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research, ELAN, Ferring, Genentech, GlaxoSmithKline, Janssen, Millennium, MSD, Ocera Therapeutics, Otsuka America Pharmaceuticals, Pfizer, Shire Pharmaceuticals, Prometheus, Robarts Clinical Trials, Schering-Plough, Synta Pharmaceuticals, Takeda, Teva, UCB Pharma and Warner Chilcott. GR is a consultant for Abbott, AbbVie, Augurix, Boehringer, Calypso, FALK, Ferring, Fisher, Genentech, Essex/MSD, Novartis, Pfizer, Phadia, Roche, Takeda, Tillots, UCB, Vifor, Vital Solutions and Zeller; received speaker honoraria from AstraZeneca, Abbott, AbbVie, FALK, MSD, Phadia, Tillots, UCB and Vifor; and received educational grants and research grants from Abbot, AbbVie, Ardeypharm, Augurix, Calypso, Essex/MSD, FALK, Flamentera, Novartis, Roche, Takeda, Tillots, UCB and Zeller. AK received educational grants from AbbVie, MSD and Takeda. PD participated in advisory boards for, and received fees and grants from, AbbVie, Biofortis, BioMérieux Danone, Ferring, Genfit, Intralytix, Kitozyme, Lesaffre, MSD, Norgine, OmegaPharma International, Pileje, PPM, Roquette, Takeda and TxCell. RWL participated in advisory boards for AbbVie, Aspen, Ferring, Janssen, Hospira and Takeda and received research support from Janssen, NHMRC Career Development Fellowship and Shire. SS received consultancy fees from AbbVie, Bristol-Myers Squibb, Boehringer, Ferring, Genentech/Roche, Pfizer, MSD/Janssen, Takeda and UCB and lecture fees from AbbVie, MSD/Janssen, Takeda and UCB. AB, MKM, CL, NR and JB are all employees of Pfizer Inc and hold stock or options in Pfizer Inc. GMC and FC are former employees of Pfizer Inc and FC is a current employee of Shire Pharmaceuticals. GF has no conflicts of interest to report. GMC has been a consultant for Adare, Albireo, AstraZeneca, CinRx, Cutis, OrphoMed, Second Genome, Strongbridge and Zealand.

Figures

Figure 1
Figure 1
Patient disposition. AE, adverse event; ITT, intent to treat; OLE, open-label extension.
Figure 2
Figure 2
Primary end point: CDAI-70 response rates at weeks 8 and 12 (generalised linear mixed model; modified intention-to-treat population). *P<0.05 versus placebo. CDAI, Crohn’s Disease Activity Index; CDAI-70, proportion of patients who achieved a ≥70-point reduction in CDAI score.
Figure 3
Figure 3
CDAI outcomes from week 2 to week 12 by treatment group: (A) CDAI-70 response rate; (B) CDAI-100 response rate; (C) CDAI remission rate; and (D) mean changes in CDAI score from baseline (generalised linear mixed model; modified intention-to-treat population). *P<0.05 versus placebo. CDAI, Crohn’s Disease Activity Index; CDAI-70/100, proportion of patients who achieved a 70/100-point reduction in CDAI score.
See this image and copyright information in PMC

References

    1. Colombel JF, Sandborn WJ, Rutgeerts P, et al. . Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007;132:52–65. 10.1053/j.gastro.2006.11.041 - DOI - PubMed
    1. Hanauer SB, Feagan BG, Lichtenstein GR, et al. . Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002;359:1541–9. 10.1016/S0140-6736(02)08512-4 - DOI - PubMed
    1. Sandborn WJ, Feagan BG, Stoinov S, et al. . Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 2007;357:228–38. 10.1056/NEJMoa067594 - DOI - PubMed
    1. Targan SR, Feagan BG, Fedorak RN, et al. . Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE Trial. Gastroenterology 2007;132:1672–83. 10.1053/j.gastro.2007.03.024 - DOI - PubMed
    1. Ding NS, Hart A, De Cruz P. Systematic review: predicting and optimising response to anti-TNF therapy in Crohn’s disease - algorithm for practical management. Aliment Pharmacol Ther 2016;43:30–51. 10.1111/apt.13445 - DOI - PubMed

Publication types

Substances

Associated data

LinkOut - more resources