Adalimumab for the treatment of Crohn's disease

Abstract

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract. Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.

Aims: To review the available data on ADA in CD for biological properties, efficacy, and safety.

Methods: Electronic searches were conducted using the Pubmed and SCOPUS databases from the earliest records to April 2008. The search terms used were "adalimumab", "anti-TNF", "TNF-alpha", "biologicals", "inflammatory bowel disease", and "Crohn's disease". Reference lists of all relevant articles were searched for further studies.

Results: Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD, both in anti-TNF-naïve patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure (although no specific randomized trials are available). No concomitant immunosuppressors seem to be necessary. Side effects appear similar to IFX, while site-injection reactions are frequent and specific. Data on immunogenicity and its clinical impact are uncertain.

Conclusions: ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX. Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD. The impact on clinical management or on resources should be more studied.

Keywords: Crohn’s disease; adalimumab; anti-TNF; biologics; treatment.

Figure 1

Efficacy of adalimumab (ADA) as induction therapy in CLASSIC I trial for Crohn’s disease. Derived from Hanauer et al (2006). *p = 0.001; **p = 0.002; ^p < 0.05; °p = 0.01; °°p = 0.007.

Figure 2

Efficacy of adalimumab (ADA) as a maintenance therapy for Crohn’s disease in the CHARM trial. Derived from Colombel et al (2007). p ≤ 0.001 for pairwise comparisons of each active treatment group vs placebo at all end points.