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Humanized antibody to the alpha4beta7 integrin for induction of remission in ulcerative colitis

  • Review
  • Intervention

Authors


Abstract

Background

Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. MLN-02, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that MLN-02 may be a useful therapy for ulcerative colitis. This systematic review summarizes the current evidence on the use of MLN-02 for induction of remission in ulcerative colitis.

Objectives

To determine the efficacy and safety of MLN-02 for induction of remission in ulcerative colitis.

Search methods

A computer-assisted search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed to identify relevant publications. References from recent reviews and published articles were searched to identify additional citations. Manual searches to identify key conference abstracts were performed. Unpublished data from on-going trials were identified by correspondence with authors and experts in the field and from the manufacturer of MLN-02.

Selection criteria

Randomized controlled trials comparing MLN-02 to placebo or a control therapy for the induction of remission in ulcerative colitis were included.

Data collection and analysis

Two independent reviewers performed data extraction and assessment of the methodological quality of each trial. Data were analyzed using Review Manager (RevMan 4.2).

Main results

One study satisfied the inclusion criteria for this review. In this study, MLN-02 was found to be effective for induction of clinical response (RR = 1.78, 95% CI 1.22 to 2.60) and remission (RR = 2.25, 95% CI 1.17 to 4.36) in patients with moderately severe ulcerative colitis. Patients receiving MLN-02 had higher IBDQ scores than patients receiving placebo. There was a trend toward increased endoscopic remission with MLN-02 relative to placebo, although this difference was not statistically significant (total MLN-02 20% versus placebo 8%; P = 0.05; RR = 2.46, 95% CI 0.98 to 6.15). Adverse events occurred in a similar proportion of patients treated with MLN-02 compared to placebo (RR = 1.60, 95% CI 0.67 to 3.83). Neutralizing antibodies were found in a significant proportion of patients receiving MLN-02, and in the group of patients with high antibody titers clinical remission rates were no different than placebo. No opportunistic infections were reported.

Authors' conclusions

Data from one trial suggests that MLN-02 may be effective for induction of clinical response and remission in patients with moderately severe ulcerative colitis. Adverse events appear to be similar to placebo, although immunogenicity may be an issue. Further trials are needed to confirm the results of this study and to define the optimal dose and frequency of administration of MLN-02.

Plain language summary

MLN-02 for the treatment of active ulcerative colitis

Ulcerative colitis is a chronic inflammatory disease of the colon. MLN-02 is a synthetic antibody that blocks the adhesion and migration of white blood cells into the gut, reducing intestinal inflammation. One study met criteria for review. This six-week study tested 181 people over the age of eighteen who had active ulcerative colitis. The patients received two intravenous infusions of MLN-02 (0.5mg/kg or 2mg/kg) or placebo (fake infusions). This single study suggests MLN-02 may be beneficial in patients with active ulcerative colitis. Clinical response (improvement of symptoms) was reported in 59% of patients receiving MLN-02 compared with 33% of patients receiving placebo. Clinical remission was reported in 32% of patients receiving MLN-02 compared to 14% of patients receiving placebo. The medication was generally well tolerated. The study results suggest MLN-02 is safe but further data will be needed to confirm these results. Side effects were reported in similar numbers of patients receiving MLN-02 and placebo. The most common side effects included worsening ulcerative colitis symptoms, nausea, and headache. Serious side effects were reported in 15% of patients receiving MLN-02 and 10% of patients receiving placebo, and most commonly was due to worsening of colitis. Serious infections were reported in three patients receiving MLN-02. One allergic reaction occurred in a patient receiving MLN-02. In conclusion, this study suggests MLN-02 may be an effective therapy for patients with active ulcerative colitis. Additional studies are needed to confirm these results.