Occasionally a parent will express concern that their child may run out of effective treatments for inflammatory bowel. At this time, there are a limited number of effective therapies. If a patient develops reactions or antibodies to medications and/or does not have a clinical response, then the options become quite limited.
Against this backdrop, it is encouraging that new medical treatments are being tested, including Vedolizumab (Inflamm Bowel Dis 2012; 18: 1470-79).
The cited study reports the experience of using Vedolizumab in a randomized controlled phase 2 dose-ranging study in 46 patients (9 placebo, 37 vedolizumab).
Vedolizumab is “a gut-selective monoclonal antibody that antagonizes α4β7 integrin on select subsets of leukocytes binding to MAdCAM-1 on gut vascular endothelium.” Many have considered vedolizumab to be similar to natalizumab, except it is considered gut-specific and therefore should not increase the risk of progressive multifocal leukoencephalopathy (PML). By altering the immune surveillance/lymphocyte tracking of the GI tract and not the brain, theoretically there should not be an increased risk of PML.
Another previous limitation of vedolizumab in small studies was the development of human antihuman antibodies (HAHA) –no joke! HAHA occurred in up to 44% of patients in previous studies and were associated with reduced efficacy. As a consequence, a new formulation of vedolizumab has been developed with presumably reduced immunogenicity.
In the cited study, patients between 18-70 were recruited to receive one to three doses of vedolizumab (2, 6, or 10 mg/kg) or placebo.
- Over 50% of vedolizumab-treated patients maintained a clinical response between days 29-253 whereas placebo response ranged between 22-33%.
- This study was not powered for efficacy; however, the treated patients did have reduced fecal calprotectin. At baseline, the calprotectin in the treatment groups averaged 405 μg/g and by day 113 had reduced to 54 μg/g. In contrast, placebo group started with calprotectin of 310 μg/g and dropped to 192 μg/g during same time period.
- HAHA were detected in 4 (11%)
According to a presentation at DDW (GEMINI I trial), more than 2500 patients have been treated in trials with vedolizumab. None has developed PML. Encouraging results for efficacy (dosing 300mg IV q4weeks) were also noted; 1 year clinical remission noted in 45% of treated patients compared with 14% of placebo group. Digestive Disease Week 2012 – Vedolizumab Scores on Safety …)
Results of vedolizumab for Crohn’s disease are expected soon as well.
Related blog entries:
Quantifying Risk of PML with Natalizumab
Tofacitinib –a JAK Inhibitor for UC