Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial

被引:695
作者
Reinisch, Walter [1 ]
Sandborn, William J. [2 ]
Hommes, Daniel W. [3 ]
D'Haens, Geert [4 ]
Hanauer, Stephen [5 ]
Schreiber, Stefan [6 ]
Panaccione, Remo [7 ]
Fedorak, Richard N. [8 ]
Tighe, Mary Beth [9 ]
Huang, Bidan [9 ]
Kampman, Wendy [10 ]
Lazar, Andreas [11 ]
Thakkar, Roopal [9 ]
机构
[1] Med Univ Vienna, Vienna, Austria
[2] Mayo Clin, Rochester, MN USA
[3] Leiden Univ, Med Ctr, Leiden, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[5] Univ Chicago, Med Ctr, Chicago, IL 60637 USA
[6] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Med 1, Kiel, Germany
[7] Univ Calgary, Calgary, AB, Canada
[8] Univ Alberta, Edmonton, AB, Canada
[9] Abbott, Abbott Pk, IL USA
[10] Abbott, Maidenhead, Berks, England
[11] Abbott, Ludwigshafen, Germany
关键词
NECROSIS-FACTOR-ALPHA; INFLAMMATORY-BOWEL-DISEASE; MONOCLONAL-ANTIBODY; CROHNS-DISEASE; OPEN-LABEL; INTESTINAL INFLAMMATION; PLACEBO-RESPONSE; INFLIXIMAB; THERAPY; MAINTENANCE;
D O I
10.1136/gut.2010.221127
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 alpha (TNF), for the induction of clinical remission in anti-TNF naive 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.
引用
收藏
页码:780 / 787
页数:8
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