Jim Kling

September 27, 2015

AMSTERDAM — In patients with late-onset asthma who have elevated blood eosinophils, the anti-interleukin 5 (IL-5) antibody reslizumab can reduce exacerbations by 75% compared with placebo, according to a new analysis of data from two phase 3 trials originally published in February (Lancet. 2015;3:355-366.)

That is an unprecedented result, said Guy Brusselle, MD, PhD, professor of medicine at Ghent University Hospital, in Belgium, who presented the research here at the European Respiratory Society (ERS) International Conference 2015.

"No study has shown such a dramatic benefit of targeted add-on therapy with monoclonal antibodies," Dr Brusselle told Medscape Medical News.

Late-onset asthma was defined as occurring in those who were diagnosed with asthma after the age of 40 years. The drug also reduced exacerbations in patients younger than 40 years, but to a much lesser extent (42%).

Dr Brusselle believes that the drug confers greater benefit in older patients because in those patients, the underlying disease mechanism differs from that in younger patients. Early-onset eosinophilic asthma tends to be allergic in nature, with a mix of cytokines working to cause symptoms, he explained. Older-onset asthma owes more to air pollution, smoke, and other irritants and is driven primarily by expression of IL-5.

The original studies included 476 patients randomly assigned to receive placebo and 477 assigned to receive reslizumab; 273 patients had late-onset asthma (placebo = 130; reslizumab = 143).

Baseline eosinophil counts were similar in both groups, but older patients responded better both in terms of asthma exacerbations and forced expiratory volume in 1 second (FEV1, see Table).

Table. Stratified Analysis of Reslizumab by Patient Subgroups

  Overall Younger Than 40 Years 40 Years or Older
Rate ratio of clinical asthma exacerbations (95% confidence interval) 0.46 (0.37 - 0.58) 0.58 (0.44 - 0.76) 0.25 (0.16 - 0.40)
FEV1 improvement on reslizumab compared with placebo at 52 weeks (95% CI) 110 mL (66 - 154) 88 mL (34 - 142) 167 mL (89 - 245)


Researchers have long suspected that early-onset and late-onset asthma are fundamentally different, said Sally Wenzel, MD, director of the Asthma Institute at the University of Pittsburgh, Pennsylvania, who attended the session. "The concept that IL-5 should work well in that [late-onset] population has been around for a long time, so it was really nice to see the data presented. The exacerbation data were quite profound," Dr Wenzel told Medscape Medical News.

One attendee wondered whether the stratified analysis was really getting at differences in age of onset. Patients in the late-onset group may have had asthma for a long time, he suggested. That can result in airway remodeling, which could in turn affect the response to medication.

"The efficacy on exacerbation frequency was very impressive, but the question is, is it related to age of onset or asthma duration?” said Patrick Berger, MD, PhD, professor of pathology at University Hospital Bordeaux.

Nevertheless, the results suggest that older-onset patients could benefit from anti-IL-5 therapy. "I think we are just exploring this thing, and we have to be pragmatic. First you start with the best compound, and if it doesn't work, you try another one. Hopefully, within the next 5 to 6 years, we will have maybe five or so different biotherapies to check," Dr Berger told Medscape Medical News.

The study was funded by Teva Pharmaceutical Industries. Dr Bruselle has received lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Teva. Dr Berger has received funding from Novartis, GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim. Dr Wenzel has disclosed no relevant financial relationships.

European Respiratory Society (ERS) International Conference 2015: Abstract OA287. Presented September 27, 2015.


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