Adalimumab (CLASSIC & CHARM trial – Crohn)

  Crohn, IBD

Adalimumab in Crohn


Related articles (Crohn):
*
Azathioprine Crohn
*Methotrexate in Crohn
*Infliximab in Crohn (ACCENT I)
*Infliximab with Azathiopurine (Crohn)
*Infliximab with Methotrexate (Crohn)
*Infliximab switch to Adalimumab in Crohn (GAIN/ADHERE trial)
*Adalimumab with immunomodulator (Crohn)
*Ustekinumab (UNITI trial – Crohn – 2016)
*Vedolizumab (GEMINI II – Crohn – 2013)


Classic-I trial induction 2006

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 (IgG(1)) 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.

CHARD trial maintenance 2007

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 > or =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. Co-primary 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.

References

Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology2006;130:323–33.

Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumabfor maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology2007;132:52–65.

Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumabinducesandmaintainsmucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology2012;142:1102–11.

Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007 Sep; 56(9): 1232–1239.

LEAVE A COMMENT