Gastroenterology

Gastroenterology

Volume 132, Issue 1, January 2007, Pages 52-65
Gastroenterology

Clinical–alimentary tract
Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn’s Disease: The CHARM Trial

https://doi.org/10.1053/j.gastro.2006.11.041Get rights and content

Background & Aims: This study evaluated the efficacy and safety of adalimumab, a fully human, anti–tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn’s disease (CD). Methods: Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn’s Disease Activity Index ≥70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Coprimary end points were the percentages of randomized responders who achieved clinical remission (Crohn’s Disease Activity Index score <150) at weeks 26 and 56. Results: The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Conclusions: Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.

Section snippets

Patients

CHARM included men and women 18–75 years of age with known CD of at least 4 months’ duration (radiologic/endoscopic confirmation required) that at the screening visits was moderately to severely active, as defined by a baseline Crohn’s Disease Activity Index (CDAI) score of 220–450 points. Concurrent therapies for CD, including stable dosages (for at least 4 weeks before screening) of azathioprine, 6-mercaptopurine, methotrexate, 5-aminosalicylates, sulfasalazine, oral mesalamine, and

Patient Disposition and Baseline Characteristics

A total of 854 patients enrolled in the trial and received induction therapy with 80 mg of adalimumab at week 0 and 40 mg of adalimumab at week 2 (Figure 1). Of these, 76 withdrew before randomization at week 4. The most common reasons for study discontinuation were adverse events and lack of efficacy. The remaining 778 patients were randomized at week 4 to receive placebo (n = 261), adalimumab 40 mg every other week (n = 260), or adalimumab 40 mg weekly (n = 257). A total of 505 enrolled

Discussion

Adalimumab, a fully human immunoglobulin G1 monoclonal antibody, is effective in inducing and maintaining long-term (56-week) clinical remission in patients with moderate to severe CD who have responded to induction therapy with adalimumab. Significant treatment differences between adalimumab and placebo groups in terms of remission and CDAI 100-point and 70-point responses were noted early (within 4 weeks after randomization) and were maintained throughout the double-blind phase. Consistent

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  • Cited by (0)

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

    A list of the CHARM study investigators and sites appears in Appendix 1.

    1

    Jean-Frédéric Colombel, William Sandborn, Paul Rutgeerts, Robert Enns, Stephen Hanauer, Remo Panaccione, and Stefen Schreiber have served as consultants for Abbott Laboratories and have participated in continuing medical education events supported by unrestricted educational grants from Abbott Laboratories.

    2

    Dan Byczkowski, Ju Li, Jeffrey Kent, and Paul Pollack are employees of Abbott Laboratories.

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