Gastroenterology

Gastroenterology

Volume 142, Issue 2, February 2012, Pages 257-265.e3
Gastroenterology

Original Research
Clinical—Alimentary Tract
Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative Colitis

https://doi.org/10.1053/j.gastro.2011.10.032Get rights and content

Background & Aims

Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α. Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled, double-blind trial.

Methods

Ulcerative colitis long-term remission and maintenance with adalimumab 2 (ULTRA 2) was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with moderate-to-severe ulcerative colitis who received concurrent treatment with oral corticosteroids or immunosuppressants. Patients were stratified based on prior exposure to TNF-α antagonists (either had or had not been previously treated with anti–TNF-α) and randomly assigned to groups given adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every other week or placebo. Primary end points were remission at weeks 8 and 52.

Results

Overall rates of clinical remission at week 8 were 16.5% on adalimumab and 9.3% on placebo (P = .019); corresponding values for week 52 were 17.3% and 8.5% (P = .004). Among anti–TNF-α naïve patients, rates of remission at week 8 were 21.3% on adalimumab and 11% on placebo (P = .017); corresponding values for week 52 were 22% and 12.4% (P = .029). Among patients who had previously received anti-TNF agents, rates of remission at week 8 were 9.2% on adalimumab and 6.9% on placebo (P = .559); corresponding values for week 52 were 10.2% and 3% (P = .039). Serious adverse events occurred in 12% of patients given adalimumab or placebo. Serious infections developed in 1.6% of patients given adalimumab and 1.9% given placebo. In the group given adalimumab, 1 patient developed squamous cell carcinoma and 1 developed gastric cancer.

Conclusions

Adalimumab was safe and more effective than placebo in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis who did not have an adequate response to conventional therapy with steroids or immunosuppressants.

Section snippets

Patients

This phase 3, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 103 centers in North America, Europe, Australia, New Zealand, and Israel between November 2006 and March 2010. The protocol was approved by the institutional review board for each center. All patients gave written consent.

Eligible patients were adults with moderately-to-severely active UC for at least 3 months with a Mayo score of 6−12 points (endoscopy subscore of at least 2), despite concurrent

Patients

Supplementary Figure 1 shows the disposition of patients. The baseline characteristics were similar in the 2 groups (Table 1). Seventy-five percent (368 of 494) of patients in the overall population were currently receiving steroids and/or azathioprine/6-mercaptopurine. The remaining 25% of patients had previously failed and discontinued one or both of these agents, in the opinion of the investigator. Forty percent (199 of 494) of patients in the overall population had previously received and

Discussion

Treatment with adalimumab demonstrated significant benefits over placebo in the rates of clinical remission at weeks 8 and 52 among patients with moderate-to-severe UC who had previously failed or were currently failing steroids and/or immunosuppressive therapy with azathioprine or 6-mercaptopurine (75% of patients were currently failing these medications). Substantial benefits were also seen for clinical response, mucosal healing, steroid discontinuation, IBDQ response, and other secondary end

Acknowledgments

Medical writing support was provided in the development and revision of this article by Amy Gamelli, PhD, and Eileen-Burkhart-Hartman, PhD, of Abbott Laboratories.

References (17)

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Conflicts of interest The authors disclose the following: Dr Sandborn reports having been a consultant, study investigator, and received grant and/or research support from Abbott Laboratories, Janssen (previously CentocorOrthoBiotech), and UCB Pharma, and a consultant for Merck (previously Schering Plough). Dr Van Assche reports having been a study investigator, consultant, and received grant and/or research support from Abbott Laboratories. In addition, Dr Van Assche has served as consultant for Biogen Idec, Centocor, Ferring, Janssen-Cilag, Novartis, NovoNordisk, PDL BioPharma, Sanofi-aventis, Schering-Plough, UCB Pharma, and Zealand Pharma; has served on advisory committees for Biogen Idec, Centocor, Novartis, NovoNordisk, PDL BioPharma, and Zealand Pharma; has received research support from Ferring; and has received speaking fees from Janssen-Cilag and Schering-Plough. Dr Reinisch reports having served as an advisory board member and speaker for Abbott Laboratories. In addition, Dr Reinisch has received consulting fees from Aesca, Biogen Idec, Centocor, Ferring, Genentech, Millennium Research Group, MSD, Novartis, Schering-Plough, Shire Pharmaceuticals, and UCB Pharma; has served on advisory committees for Aesca, Biogen Idec, Centocor, Genentech, Millennium Research Group, MSD, Novartis, Schering-Plough, Shire Pharmaceuticals, and UCB; and has received speaking fees from Ferring. Dr Colombel reports having served as a study investigator, consultant, advisory board member and speaker for Abbott Laboratories. In addition, Dr Colombel has received consulting fees from ActoGeniX, Albireo Pharma, Amgen, AstraZeneca, Bayer AG, Biogen Idec, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cellerix, Centocor, Chemocentryx, Cosmo Technologies, Danone Research, Elan Pharmaceuticals, Genentech, Giuliani SpA, Given Imaging, Glaxo Smith Kline, Hutchison MediPharma, Merck Sharp and Dohme Corp., Millennium Pharmaceuticals Inc. (now Takeda), Neovacs, Ocera Therapeutics, Inc., Pfizer, Shire Pharmaceuticals, Schering-Plough, Prometheus Laboratories, Sanofi-Aventis, Synta Pharmaceuticals Corp, Teva, Therakos, UCB Pharma, and Wyeth; has served on advisory committees for Centocor, Danone, Elan, Merck Sharp and Dohme Corp., Millennium Pharmaceuticals Inc. (now Takeda), Schering-Plough, and UCB Pharma; has received speaking fees from Centocor, Elan Pharmaceuticals, Given Imaging, Otsuka America Pharmaceutical, Merck Sharp and Dohme Corp., Schering-Plough, Shire Pharmaceuticals, Tillotts Pharma and UCB Pharma; and has received grant support from Astra-Zeneca, Ferring, Schering-Plough, and UCB Pharma. Dr D'Haens reports having been a consultant, study investigator, and received grant and/or research support from Abbott Laboratories. In addition, Dr D'Haens has received consulting fees from ActoGeniX, Centocor, Chemocentryx, Cosmo Technologies, Elan Pharmaceuticals, Ferring, Given Imaging, Glaxo Smith Kline, Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals Inc. (now Takeda), Pfizer, Schering-Plough, Shire Pharmaceuticals, Vifor and UCB Pharma. Dr Wolf reports having served as a study investigator and consultant and received grant and/or research support and speaking fees from Abbott Laboratories. In addition, Dr Wolf has received consulting fees from Bristol-Myers Squibb, Centocor, Millennium Research Group, Ortho McNeil, Prometheus Laboratories, Salix Pharmaceuticals, and UCB Pharma; has received research support from Bristol-Myers Squibb, Centocor, Millennium Research Group, Prometheus Laboratories, and UCB Pharma; has served on advisory committees for Millennium Research Group; and has received speaking fees from Ortho McNeil, Prometheus Laboratories, and UCB Pharma. Drs Kron, Tighe, Lazar, and Thakkar are employees of and own stock in Abbott.

Funding This study was sponsored by Abbott Laboratories.

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