Mepolizumab safety profile comparable with placebo across 32 studies, multiple indications
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Key takeaways:
- The retrospective analysis included 26 clinical studies of approved indications.
- Treatment discontinuations for severe adverse events included 2% of the treatment and placebo groups alike.
SAN DIEGO — Rates of serious adverse events for patients on mepolizumab were comparable with those using placebo across 7,429 patient-years of exposure, according to a presentation at the American Thoracic Society International Conference.
These rates remained comparable across multiple indications, Ian Pavord, MA, DM, FRCP, FMedSci, professor of respiratory medicine, Nuffield Department of Medicine, University of Oxford, and colleagues wrote.
“Mepolizumab has been used for years now, so there’s a lot of long-term treatment experience,” Pavord told Healio. “There really isn’t a safety signal that’s emerged over the past 10 years that this drug’s been used.”
The review analyzed safety data from 4,175 patients (53% female; mean age, 47.3 years) who used mepolizumab (Nucala, GSK) or placebo in 32 clinical studies.
Applications included severe asthma (14 studies), non-severe asthma (six studies), hypereosinophilic syndrome (seven studies), eosinophilic granulomatosis with polyangiitis (three studies) and chronic rhinosinusitis with nasal polyps (two studies).
Mepolizumab was administered to 3,402 patients overall, including 3,035 who were treated for approved indications, in a range of subcutaneous and intravenous doses.
The 7,429 patient-years of exposure to mepolizumab included 4,857.25 for severe asthma (with 4,936 for asthma overall), 1,910 for hypereosinophilic syndrome, 366 for eosinophilic granulomatosis with polyangiitis and 216 for CRSwNP.
Median exposures to mepolizumab included 14.8 (range, 1-120) months for severe asthma, 17.8 (range, 1-201) months for hypereosinophilic syndrome, 33.3 (range, 1-65) months for eosinophilic granulomatosis and 12 (range, 1-15) months for chronic rhinosinusitis with nasal polyps.
“Most of the adverse events were commoner with placebo with active treatment,” Pavord said.
Asthma (exacerbation) and pneumonia were the most common serious adverse events on treatment across all indications. Exposure-adjusted rates of serious adverse events per 1,000 patient-years included 46.9 for asthma and 9.9 for pneumonia with mepolizumab and 100.7 for asthma and 15.6 for pneumonia with placebo.
Also, across all indications, 20% of patients on any dose of mepolizumab and 11% of those on placebo reported serious adverse events. Exposure-adjusted rates per 1,000 patient-years included 285.4 for the placebo group and 238.6 for the mepolizumab group.
Specifically for severe asthma, exposure-adjusted rates per 1,000 patient-years included 168.2 with mepolizumab and 315.3 with placebo. For eosinophilic granulomatosis with polyangiitis, these rates included 317 with mepolizumab and 600.8 with placebo.
Rates for patients with hypereosinophilic syndrome included 415.6 with mepolizumab and 335.4 with placebo. Among patients with chronic rhinosinusitis with nasal polyps, rates included 124.7 with mepolizumab and 86.8 with placebo.
Rates of treatment discontinuations due to serious adverse events in approved indications included 2% both for the placebo group (n = 1,371) and for the mepolizumab group (n = 3,035).
These comparable rates of serious adverse events between treatment and placebo groups across multiple studies and indications indicate mepolizumab’s overall robust safety profile, the researchers concluded.
“One of the advantages of monoclonal antibodies is they’re very targeted, so we wouldn’t anticipate side effects,” Pavord said.
Also, Pavord said, the alternative to mepolizumab for these indications would be corticosteroids, which come with significant side effects.
Pavord additionally said post-marketing surveillance will continue and that further studies are needed for pregnancy, which has reassuring but limited evidence of safety.
“But that’s always a difficult area,” he said.
Pavord also noted that the data on pediatric use of mepolizumab were very limited in this review.
“It tends to not work that well in early onset asthma, so other biologics tend to be used,” he said. “We’re less confident about safety there.”
Still, Pavord remained confident about mepolizumab’s safety across multiple indications.
“The bottom line is it’s been a very safe and effective treatment,” he said. “We’re very lucky to have biologics that don’t seem to cause any side effects of any significance.”