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| |  Anti-IL-5 Therapy Mepolizumab Effective, Well Tolerated in Paediatric Eosinophilic Oesophagitis: Presented at GASTRO 2009 (UEGW/WCOG) By Sara Freeman LONDON-- December 1, 2009 -- Phase 2 study findings suggest that mepolizumab, a monoclonal antibody that targets interleukin (IL)-5, is not only well tolerated, but also clinically effective in children with eosinophilic oesophagitis, according to research presented here at GASTRO 2009. After 12 weeks of treatment, mepolizumab significantly reduced the peak and mean number of eosinophils present in the oesophagus compared with baseline levels, and this translated into a clinical improvement in troublesome symptoms, including pain in the chest and/or throat. “All doses of mepolizumab were well tolerated,” said Mike Thomson, MD, Sheffield Children’s Hospital, Sheffield, United Kingdom, reporting here on November 23. He added that although one or more adverse events were reported in 86% of the 59 children (aged 2-17 years) studied, “no adverse event appeared to be dose-related.” The objective of the randomised, multicentre study reported by Dr. Thomson was to assess the safety and pharmacodynamics of mepolizumab in children with active eosinophilic oesophagitis who had previously not responded to, or shown intolerance of, other therapies. Every month for 3 months, subjects were given an intravenous infusion of the novel agent, at a dose of 0.55, 2.5, or 10 mg/kg. Endoscopy with biopsy was performed 2 weeks before any treatment was given, and again at weeks 12 and 24. One of the primary endpoints was safety. Common adverse events reported included vomiting, diarrhoea, abdominal pain, nausea, nasopharyngitis, cough, oropharyngeal pain, headache, and pyrexia. However, there was no clear relationship between the occurrence of these side effects and the dose of mepolizumab used. There were no deaths, but 3 serious adverse events occurred -- chest discomfort, oesophageal injury during upper endoscopy, and food lodged in the throat; these were deemed unrelated to the experimental treatment. “Marked reductions in mean and peak oesophageal eosinophil counts were observed at week 12,” Dr. Thomson said, adding that “the magnitude of response was similar at all 3 doses.” Five (8.5%) children achieved the primary endpoint of having fewer than 5 eosinophils present per high-powered field upon microscopic examination of oesophageal biopsy specimens. While reductions in peak eosinophil counts were seen at week 12, “the magnitude of response is generally not sustained at week 24,” Dr. Thomson observed. He noted, however, that the reductions in eosinophil counts achieved with the 2.5- and 10-mg/kg doses did appear to last longer than those seen with the lowest (0.55 mg/kg) mepolizumab dose tested. “There was a low symptom frequency and severity in most subjects at baseline,” Dr. Thomson said, with “trends towards improvement observed.” The clinical relevance of this, however, remains unclear. Dr. Thomson concluded, “Mepolizumab was safe and well tolerated in these paediatric subjects.” Funding for this study was provided by GlaxoSmithKline. GASTRO 2009 is jointly organised by the United European Gastroenterology Federation (UEGF), the World Gastroenterology Organisation (WGO), the World Organisation of Digestive Endoscopy (OMED), and the British Society of Gastroenterology (BSG). [Presentation title: Safety and Pharmacodynamics of Mepolizumab, a Humanised Monoclonal Antibody Against IL-5, in Paediatric Subjects With Eosinophilic Oesophagitis: A Randomised, Double-Blind, Controlled Clinical Trial. Abstract OP002]
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