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Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial
  1. Walter Reinisch1,
  2. William J Sandborn2,
  3. Daniel W Hommes3,
  4. Geert D'Haens4,
  5. Stephen Hanauer5,
  6. Stefan Schreiber6,
  7. Remo Panaccione7,
  8. Richard N Fedorak8,
  9. Mary Beth Tighe9,
  10. Bidan Huang9,
  11. Wendy Kampman10,
  12. Andreas Lazar11,
  13. Roopal Thakkar9
  1. 1Medical University Vienna, Vienna, Austria
  2. 2Mayo Clinic, Rochester, Minnesota, USA
  3. 3Leiden University Medical Center, Leiden, Netherlands
  4. 4Academic Medical Centre, Amsterdam, Netherlands
  5. 5University of Chicago Medical Center, Chicago, Illinois, USA
  6. 6Christian-Albrechts-University, University-Hospital Schleswig-Holstein, Medical Department I, Kiel, Germany
  7. 7University of Calgary, Calgary, AB, Canada
  8. 8University of Alberta, Edmonton, AB, Canada
  9. 9Abbott, Abbott Park, Illinois, USA
  10. 10Abbott, Maidenhead, UK
  11. 11Abbott, Ludwigshafen, Germany
  1. Correspondence to Dr Walter Reinisch, Universitätsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie, Waehringer Guertel 18-20, A-1090 Vienna, Austria; walter.reinisch{at}meduniwien.ac.at

Abstract

Objective The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor α (TNF), for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis.

Methods This 8-week, multicentre, randomised, double-blind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1:1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score ≤2 with no individual subscore >1) at week 8, assessed in 390 patients randomised (1:1:1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment.

Results At week 8, 18.5% of patients in the ADA160/80 group (p=0.031 vs placebo) and 10.0% in the ADA80/40 group (p=0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths.

Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants.

Clinical trial NCT00385736.

  • Antibody targeted therapy
  • clinical trials
  • ulcerative colitis

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Footnotes

  • See Commentary, p 741

  • Linked articles 233403.

  • Funding This study was funded by Abbott.

  • Competing interests The authors declare that WR, WJS, DH, GD, SH, SS, RP and RNF have received support from Abbott for the submitted work; and MBT, BH, WK, AL and RT are employees of Abbott.

  • Ethics approval This study was conducted with the approval of the institutional review board for each participating site, and carried out according to guidelines of the International Conference on Harmonization and the ethical principles originating in the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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