Dupilumab leads biologics in reducing asthma exacerbations

Key takeaways:

• Dupilumab users had at least 0.5 fewer exacerbations per person per 1.5 years compared with other biologics.
• Impacts were greater among patients with histories of two or more exacerbations.

Biologics designed to counter type 2 inflammation reduced asthma exacerbations in real world settings, with dupilumab having the most impact, according to a study in The Journal of Allergy and Clinical Immunology: In Practice.

Treatment also was most effective for patients with high exacerbation burdens, Taha Al-Shaikhly, MBChB, assistant professor, section of allergy, asthma and immunology, department of medicine, Penn State College of Medicine, and colleagues wrote.

The researchers identified 5,538 adults aged 18 to 63 years (mean age, 45.6 years; 65.8% women) who received a biologic agent for asthma between Jan. 1, 2016, and June 30, 2019, as reported by the IBM MarketScan Commercial Claims and Encounters Database from Merative.

The cohort included 2,780 (50.2%) who received omalizumab (Xolair; Genentech, Novartis), 1,084 (15%) who received mepolizumab (Nucala, GSK), 1,055 (12.7%) who received dupilumab (Dupixent; Regeneron, Sanofi), 556 (9%) who received benralizumab (Fasenra, AstraZeneca) and 63 (1.12%) who received reslizumab (Cinqair, Teva Pharmaceutical).

When researchers compared the year before the indexed biologic start date and the year afterward, they found an average reduction of 34% in the mean number of exacerbations per person. These reductions included 47.2% for dupilumab, 24.5% for mepolizumab, 44.4% for reslizumab, 42.8% for benralizumab and 11.2% for omalizumab.

Effects were greater for patients with histories of two or more exacerbations during the enrollment period, with an average 48.5% reduction overall and reductions of 65.3% with dupilumab, 37.3% for mepolizumab, 56.2% for reslizumab, 52.5% for benralizumab and 31% for omalizumab.

Reductions in mean numbers of outpatient asthma-related corticosteroid use ranged from 2.2% for omalizumab to 44.2% for dupilumab.

Similarly, reductions in mean numbers of asthma-related ED visits ranged from 31.8% for dupilumab to 59.1% for reslizumab.

Reductions in mean numbers of asthma-related hospitalizations per person ranged from 44.6% for mepolizumab to 73.3% for reslizumab.

Compared with the other biologics, dupilumab was associated with 0.5 fewer asthma exacerbations per person per 1.5 years. Omalizumab had the next fewer asthma exacerbations per person per 1.5 years, followed by mepolizumab, reslizumab and benralizumab.

Efficacy appeared relatively better for benralizumab compared with omalizumab (adjusted estimate, –0.46; 95% CI, –0.54 to –0.37) and mepolizumab (adjusted estimate, –0.43; 95% CI, –0.52 to –0.35), the researchers wrote, but there were no differences when mepolizumab and reslizumab were compared with omalizumab.

Patients who used dupilumab had the lowest adjusted odds ratio for experiencing two or more exacerbations compared with the other biologics. Also, patients who used benralizumab had lower adjusted odds ratios for two or more exacerbations compared with patients who used mepolizumab (adjusted OR = 0.45; 95% CI, 0.35-0.57) and with those who used omalizumab (aOR = 0.5; 95% CI, 0.4-0.63).

Among patients who had used inhaled corticosteroids (ICS) and long-acting beta agonists (LABA), those who also used dupilumab had lower odds for experiencing two or more exacerbations as well, compared with those who used other biologics.

However, the better efficacy reported among patients who used benralizumab compared with those who used mepolizumab or omalizumab did not persist among patients who also used ICS and LABA or among those with two or more exacerbations.

Dupilumab additionally was associated with less asthma-related systemic corticosteroid use as well as fewer ED visits and hospitalizations related to asthma than the other biologics, the researchers wrote.

However, the researchers added, this effect was less pronounced after the odds for two or more exacerbations and asthma-related outpatient systemic corticosteroid use, ED visits and hospitalizations were assessed.

Overall increases in asthma-related costs associated with the use of these biologic treatments likely reflect the costs of these drugs, the researchers said, although there was no apparent influence of biologic class on these overall costs.

Still, the researchers said, patients who used benralizumab had a statistically significant but marginal savings per patient over 18 months, compared with patients who used dupilumab.

Based on these findings, the researchers concluded that biologics that target type 2 inflammation were effective in reducing exacerbations, especially for patients with high exacerbation burdens, while also reducing ED visits and hospitalizations related to asthma.

The researchers also attributed dupilumab’s superior performance in many of these metrics to its targeting of IL-4R alpha, which is shared by IL-4 and IL-13 and therefore part of several key steps in type 2 inflammation, compared with the other biologics’ more limited targets such as IgE and IL-5.

Although such a study would be difficult, the researchers said, a head-to-head controlled study of these biologics would be needed to confirm these findings.