Natalizumab for Induction of Remission in Crohnʼs Disease

Abstract

Purpose: Natalizumab is a recombinant humanized antibody derived from murine monoclonal antibody raised against human α4 integrin. Recent studies have reported that natalizumab might be effective for the treatment of active Crohn's disease. We conducted a meta-analysis to analyze the efficacy and safety of Natalizumab for induction of remission in Crohn's disease. Methods: A thorough literature search was conducted on Medline and Cochrane Clinical Trials Registry of all published randomized clinical trials (RCTs) 1966 to 2006. Abstracts of gastroenterology scientific meetings were hand searched. 2 independent reviewers assessed the studies. Standard forms were used to extract data regarding study design, outcome measures, and adverse effects. Mantel–Haenszel method (fixed-effects model) was used for pooling trial results. Results: 3 RCTs satisfied the inclusion criteria (1183 pts). No significant heterogeneity was present among the studies (I2 = 0%). 2 studies evaluated moderate to severe Crohn's disease, while one study evaluated mild to moderately active disease. The efficacy was evaluated by using the Crohn's Disease Activity Index (CDAI). Doses studied were 3mg/kg, 6mg/kg and 300mg. Patients were given a single infusion of Natalizumab in 1 study, 2 infusions in another and 3 infusions in the third trial. All the studies measured the primary end points at different times (2, 8 and 10 wks). Natalizumab showed higher rate of induction of remission in comparison to placebo at the study defined primary end points (RR = 1.27.CI = 1.03 to 1.57). Natalizumab also continued to show higher rate of induction of remission after 12 weeks of therapy (RR = 1.32.CI = 1.07 to 1.62). Health related quality of life and C-Reactive Proteins levels improved with Natalizumab compared to placebo. Overall, Natalizumab was well tolerated. Headache was one of the most common side effects. 7% of patients treated with Natalizumab developed antibodies against the drug. Acute infusion reactions occurred in 9% of the patients. There was no significant increase in the risk of infection among the patients treated with Natalizumab. 1 patient developed progressive multifocal leukoencephalopathy after therapy with Natalizumab. Conclusions: Natalizumab induces clinical remission in Crohn's disease. Further studies are needed to confirm the findings and also to better define the safety profile of Natalizumab.