Gastroenterology

Gastroenterology

Volume 130, Issue 2, February 2006, Pages 323-333
Gastroenterology

Clinical–alimentary tract
Human Anti–Tumor Necrosis Factor Monoclonal Antibody (Adalimumab) in Crohn’s Disease: the CLASSIC-I Trial

https://doi.org/10.1053/j.gastro.2005.11.030Get rights and content

Background & Aims: Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn’s disease (CD). Adalimumab is a human immunoglobulin G1 (IgG1) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD. Methods: A total of 299 patients with moderate to severe CD naive to anti–TNF therapy were randomized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 (defined as a Crohn’s Disease Activity Index score <150 points) among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups. Results: The rates of remission at week 4 in the adalimumab 40 mg/20 mg, 80 mg/40 mg, and 160 mg/80 mg groups were 18% (P = .36), 24% (P = .06), and 36% (P = .001), respectively, and 12% in the placebo group. Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients. Conclusions: Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn’s disease naive to anti–TNF therapy. The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2. Adalimumab was well tolerated.

Section snippets

Patients

This multicenter, randomized, double-blind, placebo-controlled trial was conducted at 55 centers between July 24, 2002, and December 18, 2003. The protocol was approved by the institutional review board or ethics committee at each center. All patients gave written informed consent.

Eligible patients included men and women (18–75 years of age) with Crohn’s disease for at least 4 months who had moderate to severe disease as defined by a Crohn’s Disease Activity Index (CDAI)24 score of 220–450

Characteristics of the Patients

A total of 299 patients were available for randomization at week 0 (Figure 1). The 299 patients were randomly assigned to receive placebo induction (74 patients) or adalimumab induction with 40 mg/20 mg (74 patients), 80 mg/40 mg (75 patients), or 160 mg/80 mg (76 patients). The baseline characteristics of the patients who received placebo were similar to those who received adalimumab (Table 1). Overall, premature withdrawal from the study occurred in 6 patients (8%) in the placebo group versus

Discussion

We found that induction therapy with adalimumab, administered subcutaneously as a loading dose at week 0 followed by a second dose at week 2, is superior to placebo for inducing remission and response in infliximab-naive patients with moderate to severe disease activity despite the use of conventional therapy. Patients who received the highest dose (160 mg/80 mg) of adalimumab were 3 times more likely to achieve remission and approximately twice as likely to achieve a 100-point response and

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    Supported by a research grant from Abbott Laboratories (Abbott Park, IL).

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    S.B.H., W.J.S., P.R., R.N.F., R.P., and D.W. have served as consultants for Abbott Laboratories. S.B.H., W.J.S., P.R., R.N.F., and R.P. have participated in continuing medical education events supported by unrestricted educational grants from Abbott Laboratories.

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