From the Journals
Dupilumab reduces exacerbations, cuts glucocorticoid use in moderate to severe asthma
Evidence of lung remodeling was observed in patients with severe asthma in a trial of a anti–interleukin-4 alpha antibody drug.
PARIS – Severe asthma patients with chronic rhinosinusitis (CRS), nasal polyposis (NP), or both derive more protection from severe exacerbations with the monoclonal antibody dupilumab than do those who do not have these comorbidities, according to a post hoc analysis of a phase 3 trial presented at the annual congress of the European Respiratory Society.
Ted Bosworth/MDedge News
Dr. Ian Pavord
“Dupilumab reduced rates of severe exacerbations and improved FEV1 [forced expiratory volume in 1 second] in patients in asthma patients with or without CRS/NP. In those with CRS/NP, dupilumab reduced symptoms associated with these comorbidities,” reported Ian Pavord, MBBS, statutory chair in respiratory medicine at University of Oxford (England).
The data were drawn from the phase 3 Liberty Asthma Quest trial, which was published earlier this year in the New England Journal of Medicine (2018;378:2486-96). In that study, both the 200-mg and 300-mg dose of dupilumab (Dupixent) administered every 2 weeks was associated with about a 50% reduction in the annualized rate of severe exacerbations relative to placebo (P less than .001 for both doses).
In this new post hoc analysis, response in the 382 patients who entered the study with a history of CRS/NP was compared with the 1,520 without CRS/NP. In the CRS/NP patients, the reductions relative to placebo in the rates of severe exacerbations, defined as 3 or more days of systemic glucocorticoids or visit to an emergency department leading to treatment with systemic glucocorticoids, were 63% and 61% for the 200-mg and 300-mg doses of dupilumab, respectively (both P less than .001).
In the non-CRS/NP arms, the reductions relative to placebo were 42% and 40%, respectively (both P less than .001). The greater relative reductions in the CRS/NP patients were achieved even though they were older (mean age approximately 52 vs. 47 years for non-CRS/NP patients), had a significantly greater number of exacerbations in the past year (P = .027), and had higher baseline fractional exhaled nitric oxide and eosinophil levels (both P less than .001), Dr. Pavord reported.
“The greater asthma severity in the CRS/NP patients in this trial is consistent with that reported previously by others,” Dr. Pavord said.
Although the greater asthma severity may have provided a larger margin for benefit, Dr. Pavord also reported that there were improvements in CRS/NP-specific symptoms as measured with the 22-item Sino-Nasal Outcome Test (SNOT-22). By week 12, the total score reduction in SNOT-22 was approximately 15 points (P less than .05) from baseline for both the 200-mg and 300-mg dupilumab doses. This was significantly greater (P less than .05) relative to modest SNOT-22 reductions in the placebo arms (P less than .05). After 52 weeks, the reduction In SNOT-22 scores were sustained, providing an even greater statistical advantage over placebo (P less than .001).
In addition to greater protection against severe exacerbations and CRS/NP-specific symptoms, dupilumab may offer specific improvements on CRS/NP pathology, according to Dr. Pavord. Although imaging was not part of this study, he noted in particular that previous studies with dupilumab as well as other biologics have shown shrinkage of nasal polyps with treatment.
Dupilumab was similarly well tolerated in those with and without CRS/NP. The most common adverse event was injection site reactions in both groups, Dr. Pavord said.
Calling CRS and NP “important comorbidities” in severe asthma patients, Dr. Pavord said that this analysis should be reassuring for those who with CRS/NP who are being considered for dupilumab. Already approved for treatment of atopic dermatitis, dupilumab, which binds to interleukin-4 (IL-4) and IL-13 receptors, is currently under review for the treatment of moderate to severe asthma.
Dr. Pavord has financial relationships with Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Knapp, Merck Sharpe, Novartis, Knapp Teva, RespiVert, and Schering-Plough.