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. 2022 Nov;150(5):1097-1105.e12.
doi: 10.1016/j.jaci.2022.05.024. Epub 2022 Jun 27.

Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis

Ayobami Akenroye  1 , Grace Lassiter  2 , John W Jackson  3 , Corinne Keet  4 , Jodi Segal  5 , G Caleb Alexander  5 , Hwanhee Hong  6
Affiliations

Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis

Ayobami Akenroye et al. J Allergy Clin Immunol. 2022 Nov.

Abstract

Background: The comparative safety and efficacy of the biologics currently approved for asthma are unclear.

Objective: We compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma.

Methods: We performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma.

Results: Eight randomized clinical trials (n = 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV1: dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, -0.63; 95% CI, -0.81 to -0.45), dupilumab (MD, -0.48; 95% CI, -0.83 to -0.14), and benralizumab (MD, -0.32; 95% CI, -0.43 to -0.21). In individuals with eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV1. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4).

Conclusion: There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma.

Keywords: Asthma; Bayesian; benralizumab; comparative effectiveness; dupilumab; eosinophilic; mepolizumab; monoclonal antibody; network meta-analysis.

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Conflict of interest statement

Disclosures:

Dr. Alexander is past Chair and a current member of FDA’s Peripheral and Central Nervous System Advisory Committee; is a co-founding Principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a past member of OptumRx’s National P&T Committee. All other authors have no conflicts of interest to disclose.

Figures

FIGURE 1:
FIGURE 1:
Surface under the cumulative ranking (SUCRA) curve with regard to the efficacy outcomes, Asthma Control Questionnaire (ACQ), exacerbation, and prebronchodilator forced expiratory volume, in 1 second (FEV1) in individuals with eosinophil count of ≥300 cells per microliter. Each plot displays the cumulative ranking probabilities of each treatment being the best (#1), second-best (#2), third-best (#3), or the worst (#4) for each outcome. The best overall treatment would be the treatment with its area under curve closest to the entire area of the graph shaped a rectangle. For example, mepolizumab was the best treatment for improving ACQ, while dupilumab was the best in reducing exacerbations and improving FEV1 in these patients.
FIGURE 2:
FIGURE 2:
Surface under the cumulative ranking (SUCRA) curve with regard to the efficacy outcomes, exacerbation and prebronchodilator forced expiratory volume in 1 second (FEV1), in individuals with eosinophil count of 150–299 cells per microliter. Each plot displays the cumulative ranking probabilities of each treatment being the best (#1), second-best (#2), third-best (#3), or the worst (#4) for each outcome. The best overall treatment would be the treatment with its area under curve closest to the entire area of the graph shaped a rectangle. For example, benralizumab and dupilumab ranked higher than mepolizumab which ranked higher than placebo in reducing exacerbations and improving FEV1 in these patients.
Figure 3:
Figure 3:
Scatter plots of the overall SUCRA score (ranking probability) of improving pairs of outcomes. (A.) Exacerbation rate reduction vs prebronchodilator forced expiratory volume in 1 second (FEV1) improvement in individuals with eosinophil count ≥ 300 and 150–299 cells/mcl; (B.) (Left panel) FEV1 improvement vs Asthma Control questionnaire (ACQ) improvement and (Right panel) Exacerbation rate reductions vs ACQ improvement in individuals with eosinophil count ≥300 cells/mcl; (C.) Overall SUCRA score for improving exacerbations vs. inverse odds of serious adverse events (SAE) in individuals with eosinophil count ≥300 and 150–299 cells/mcl; (D.) Overall SUCRA score for FEV1 vs inverse odds of SAE in individuals with eosinophil count ≥300 and 150–299 cells/mcl.
Figure 3:
Figure 3:
Scatter plots of the overall SUCRA score (ranking probability) of improving pairs of outcomes. (A.) Exacerbation rate reduction vs prebronchodilator forced expiratory volume in 1 second (FEV1) improvement in individuals with eosinophil count ≥ 300 and 150–299 cells/mcl; (B.) (Left panel) FEV1 improvement vs Asthma Control questionnaire (ACQ) improvement and (Right panel) Exacerbation rate reductions vs ACQ improvement in individuals with eosinophil count ≥300 cells/mcl; (C.) Overall SUCRA score for improving exacerbations vs. inverse odds of serious adverse events (SAE) in individuals with eosinophil count ≥300 and 150–299 cells/mcl; (D.) Overall SUCRA score for FEV1 vs inverse odds of SAE in individuals with eosinophil count ≥300 and 150–299 cells/mcl.
Figure 3:
Figure 3:
Scatter plots of the overall SUCRA score (ranking probability) of improving pairs of outcomes. (A.) Exacerbation rate reduction vs prebronchodilator forced expiratory volume in 1 second (FEV1) improvement in individuals with eosinophil count ≥ 300 and 150–299 cells/mcl; (B.) (Left panel) FEV1 improvement vs Asthma Control questionnaire (ACQ) improvement and (Right panel) Exacerbation rate reductions vs ACQ improvement in individuals with eosinophil count ≥300 cells/mcl; (C.) Overall SUCRA score for improving exacerbations vs. inverse odds of serious adverse events (SAE) in individuals with eosinophil count ≥300 and 150–299 cells/mcl; (D.) Overall SUCRA score for FEV1 vs inverse odds of SAE in individuals with eosinophil count ≥300 and 150–299 cells/mcl.
Figure 3:
Figure 3:
Scatter plots of the overall SUCRA score (ranking probability) of improving pairs of outcomes. (A.) Exacerbation rate reduction vs prebronchodilator forced expiratory volume in 1 second (FEV1) improvement in individuals with eosinophil count ≥ 300 and 150–299 cells/mcl; (B.) (Left panel) FEV1 improvement vs Asthma Control questionnaire (ACQ) improvement and (Right panel) Exacerbation rate reductions vs ACQ improvement in individuals with eosinophil count ≥300 cells/mcl; (C.) Overall SUCRA score for improving exacerbations vs. inverse odds of serious adverse events (SAE) in individuals with eosinophil count ≥300 and 150–299 cells/mcl; (D.) Overall SUCRA score for FEV1 vs inverse odds of SAE in individuals with eosinophil count ≥300 and 150–299 cells/mcl.
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References

    1. Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy. 2007;62(2):126–33. - PubMed
    1. Antonicelli L, Bucca C, Neri M, De Benedetto F, Sabbatani P, Bonifazi F, et al. Asthma severity and medical resource utilisation. Eur Respir J. 2004;23(5):723–9. - PubMed
    1. Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol. 2015;135(2):299–310; quiz 1. - PubMed
    1. Assaf SM, Hanania NA. Biological treatments for severe asthma. Curr Opin Allergy Clin Immunol. 2019;19(4):379–86. - PubMed
    1. Edris A, De Feyter S, Maes T, Joos G, Lahousse L. Monoclonal antibodies in type 2 asthma: a systematic review and network meta-analysis. Respir Res. 2019;20(1):179. - PMC - PubMed

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