Clinical Context

Although less than 10% of individuals with asthma have severe disease, these account for most asthma-related morbidity and mortality. Since 2003, several biologic agents targeting various interleukin signaling pathways have been available for those with severe disease.

In placebo-controlled trials, mepolizumab, benralizumab, and dupilumab have been shown to reduce exacerbation rates, improve lung function, and improve quality of life among individuals with severe eosinophilic asthma (SEA). Bayesian network meta-analyses allows simultaneous comparisons of these treatments, rather than pairwise comparisons, and generation of a probability-based ranking of their safety and efficacy.

Study Synopsis and Perspective

Differences in the safety and efficacy between the biologics approved for the treatment of severe eosinophilic asthma are so minimal as to not meet clinically important thresholds, a network meta-analysis shows.

"We know relatively little of the comparative effectiveness or safety of biologics approved for the treatment of asthma [but since] the number of these biologics continue to rise--and their indications are increasing--the opportunities to use these biologics will only continue to increase, and we need to know more about their comparative effectiveness to optimize their use," Ayobami Akenroye, MD, MPH, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, told Medscape Medical News in an email.

"But the decision to use one biologic or not is complex and goes beyond comparative effectiveness, and factors such as insurance coverage, convenience of self-administration, and comorbidities all play a role in the choice of biologics," she said. She noted that all the outcomes assessed in the study contribute to or reflect a patient's underlying asthma control.

The study was published online June 27 in the Journal of Allergy and Clinical Immunology.

Drugs that target various interleukin signaling pathways involved in the pathogenesis of asthma include mepolizumab, benralizumab, and dupilumab, all of which have been shown to decrease exacerbation rates, improve lung function, and enhance quality of life for patients with severe eosinophilic asthma. In a Bayesian network meta-analysis that allows for simultaneous comparisons of these 3 treatments, investigators analyzed 8 randomized, placebo-controlled trials that compared each of the drugs with placebo. In total, the trials involved 6461 patients; the duration of follow-up was between 24 and 56 weeks.

"In the subgroup of patients with eosinophil counts of ≥300 cells/mcL, all three biologics were significantly better than placebo in reducing exacerbations," Dr Akenroye and colleagues report. For example, dupilumab reduced the exacerbation risk by 68% at a risk ratio (RR) of 0.32 (95% credible interval [CI], 0.23-0.45), whereas mepolizumab reduced it by almost as much, at 63% (RR, 0.37; 95% CI, 0.30-0.45).

Benralizumab was slightly less effective than the other 2 biologics, reducing exacerbation risk by 51% (RR, 0.49; 95% CI, 0.43-0.55). "In patients with eosinophil counts of ≥300 cells/mcL, all three biologics had a probability of 1 in improving the exacerbation rate by 20% or more. . .in comparison to placebo," the authors emphasize.

Regarding each drug's effect in improving forced expiratory volume in 1 second (FEV₁), the mean difference in milliliters (MD) with dupilumab before and after treatment was 230 (95% CI, 160-300), whereas for benralizumab, the MD was 150 (95% CI, 100-220) before and after treatment. With mepolizumab, the MD in FEV₁ before and after treatment was also 150 (95% CI, 66-220). In the same subgroup of patients with eosinophil counts of at least 300 cells/μL, all 3 biologics again had a probability of 1 in improving FEV₁ by 50 mL or more above the placebo effect. A third endpoint that was analyzed was the potential reduction in Asthma Control Questionnaire (ACQ) scores. With mepolizumab, the MD before and after treatment was −0.65 (95% CI, −0.81 to −0.45), with dupilumab it was −0.48 (95% CI, −0.83 to −0.14), and with dupilumab it was −0.32 (95% CI, −0.43 to −0.21).

"Dupilumab was significantly better than benralizumab in improving exacerbations," the authors note (RR, 0.66; 95% CI, 0.47-0.94), whereas mepolizumab was also better than benralizumab (RR, 0.75; 95% CI, 0.60-0.95). In contrast, both dupilumab and benralizumab led to greater improvements in FEV₁ than mepolizumab, although the effects of dupilumab and benralizumab on ACQ scores were not significantly different for patients whose lower eosinophil counts were between 150 and 299 cells/μL.

As for safety outcomes, both mepolizumab and benralizumab were associated with a lower risk for serious adverse events, but dupilumab was not different from placebo in terms of overall safety, according to the authors.

"[However], these results may be helpful to clinicians as they optimize patient care," they conclude. Limitations to the analysis include the fact that indirect comparisons cannot replace randomized trials that compare the 3 drugs directly.

Dr Akenroye has disclosed no relevant financial relationships.

J Allergy Clin Immunol. Published online June 27, 2022.^[1]

Clinical Implications

• In SEA, efficacy and safety differences among mepolizumab, benralizumab, and dupilumab were minimal.
• The study findings offer valuable information for clinicians and patients to help balance safety and efficacy of these biologics.
• Implications for the Health Care Team: The ultimate choice of biologic for each patient depends on multiple factors including cost considerations, insurance coverage, and timing of administration. A team approach should be taken when selecting the most appropriate biologic.

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