Jim Kling

March 15, 2016

LOS ANGELES — For patients with chronic sinusitis and nasal polyps, reslizumab is particularly effective, according to a subgroup analysis of two pivotal phase 3 trials of the anti-interleukin-5 antibody.

These patients have an "unusual constellation of symptoms" and are very high users of healthcare, said Steven Weinstein, MD, director of the Allergy and Asthma Specialists Medical Group in Huntington Beach, California.

"Interleukin-5 is a major player in eosinophilic inflammation, and the study patients had high eosinophils and also severe asthma that was uncontrolled with high doses of conventional medications," he explained here at the American Academy of Allergy, Asthma and Immunology 2016 Annual Meeting.

"This population had a very strong response in terms of decreasing exacerbations and improving lung function and a variety of quality-of-life measures," Dr Weinstein told Medscape Medical News.

Reslizumab showed good efficacy in two pivotal trials of patients with elevated levels of blood eosinophils (Lancet Respir Med. 2015;3:355-366).

For their subanalysis, Dr Weinstein and his team evaluated the 953 patients from those trials, 150 (16%) of whom had chronic sinusitis with nasal polyps and 252 (26%) of whom had chronic sinusitis without nasal polyps.

The annual exacerbation rate in the overall study cohort was lower with reslizumab than with placebo.

Table. Annual Exacerbation Rate With Reslizumab, Compared With Placebo

Patient Group Decrease, % Relative Risk 95% Confidence Interval
All 54 0.46 0.37–0.58
With nasal polyps 83 0.17 0.10–0.32
Without polyps 70 0.30 0.20–0.44

The Asthma Quality of Life Questionnaire score in the study cohort was 0.272 points higher with reslizumab than with placebo (95% CI, 0.155 - 0.388). For those with nasal polyps, the score was 0.686 higher (95% CI, 0.400 - 0.972), and for those without nasal polyps, the score was 0.466 higher (95% CI, 0.243 - 0.689).

During the 52-week study period, forced expiratory volume in 1 second (FEV₁) in study cohort was 110 mL higher (95% CI, 66 - 154) with reslizumab than with placebo. For those with nasal polyps, FEV₁ was 326 mL higher (95% CI, 210 - 441), and for those without nasal polyps, it was 235 mL higher (95% CI, 147 - 323).

The trials and subanalysis are interesting, but it is not entirely clear how these results will apply to real-world patients, said Tanya Laidlaw, MD, director of translational research in allergy at Brigham Women's Hospital and assistant professor of medicine at Harvard Medical School in Boston.

An Atypical Patient Population

As in most targeted therapy trials, the patients were carefully selected to have a high likelihood of responding, and aren't representative of what would typically be seen in the clinic, she pointed out.

Dr Laidlaw also disputed the idea that the uncontrolled asthma in the study population was in spite of high doses of conventional medications. The patients had a predicted FEV₁ of about 66%, and that went up by an average of 25% with bronchodilators. "They're highly underdosed," Dr Laidlaw told Medscape Medical News.

"The patients who are really likely to cost-effectively benefit from this medication are the ones who are already on high doses of corticosteroids and a long-acting beta agonist and who still have uncontrolled, severe asthma," she explained. "In those patients, I think an injection once a month with a multithousand dollar medication makes a lot of sense."

It remains to be seen whether patients with chronic sinusitis and nasal polyps are a distinct subpopulation of asthma sufferers, said Dr Laidlaw. "Patients with chronic sinusitis and eosinophilia and nasal polyps seem to respond much better. Is it because they have a distinct clinical phenotype that is responding individually and biologically to reslizumab in a better way than other groups, or is it because those patients are skewed toward having more of the biomarkers that we think predict the efficacy of reslizumab?"

Dr Laidlaw said she believes the drug will still have utility in the clinic. "What one really wants is a head-to-head trial with mepolizumab. My impression is that reslizumab is probably slightly more effective. For the subgroup of patients with high eosinophil counts, uncontrolled asthma despite pushing up with standard therapy, with the results that Dr Weinstein presented, I would use reslizumab," said Dr Laidlaw.

Reslizumab was rubber-stamped by the US Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee in December, and is expected to receive approval in the near future.

Dr Weinstein reports receiving research support from AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Teva Pharmaceuticals; and being a speaker and serving on the advisory board for Teva Pharmaceuticals. Dr Laidlaw has disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2016 Annual Meeting: Abstract 283. Presented March 5, 2016.


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