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Insights into choosing the right biologic for the right patient

Published online: September 11, 2018

As more and more biologics are approved for the treatment of severe asthma, the clinician is left with the dilemma of trying to pick the right biologic for the right patient. Given the cost of biologics, typically more than $25,000 per year, and the severity of the disease of the patients they are best suited for, it behooves us to try and determine if there are differences in the biologics currently available for the treatment of severe asthma in regards to therapeutic effectiveness and potential adverse consequences. This task is complicated since the characteristics of the patients enrolled in the pivotal approval studies for each biologic are different. Optimally, one would like to see head-to-head studies of each biologic in the same population of asthma patients in order to answer this question. However, due to the large number of patients one would have to recruit for these types of studies and the high risk of failure in showing clinically meaningful differences between biologics, it is unlikely that these studies will ever be done.

Network meta-analysis is an accepted method to assess comparative effectiveness when head-to-head data are unavailable. In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Casale et al conducted such an analysis to indirectly compare the efficacy and safety of two anti-IL-5 biologics, reslizumab and benralizumab, in patient populations with similar characteristics based on actual clinical trial data. The population for this analysis consisted of patients with severe eosinophilic asthma enrolled in randomized, double blinded, placebo-controlled trials of reslizumab and benralizumab. Key outcomes examined included: incidence of clinically significant asthma exacerbations; change from baseline in FEV1; patient-reported outcomes and health-related quality of life; and safety. Studies evaluating relevant doses at similar time points (~1 year) were chosen to construct the evidence network.

Since different inclusion/exclusion criteria resulted in differences among populations in the reslizumab and benralizumab studies, subgroups were analyzed to generate similar populations for analysis: a benralizumab subgroup with blood eosinophil levels ≥300 cells/μL (n = 1537) and a reslizumab subgroup in GINA step 4/5 with ≥2 prior exacerbations and ≥400 eosinophils/μL (n = 318). It should be noted that the use of subgroups resulted in a smaller sample size and limited statistical power focused on a more severe subpopulation.

Reslizumab significantly improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) scores compared with benralizumab Q4W and there were reasonably high posterior probabilities that reslizumab is superior to benralizumab Q4W and Q8W for ACQ score, AQLQ score, FEV1, and clinical asthma exacerbations. The safety analysis suggested, at a minimum, that reslizumab is no less tolerable than benralizumab.

This indirect comparison suggests reslizumab may be more efficacious than benralizumab in patients with severe eosinophilic (elevated blood eosinophil levels; benralizumab, ≥300/μL; reslizumab, ≥400/μL) asthma with ≥2 exacerbations in the previous year. In the absence of head-to-head data, indirect comparisons might help clinicians to choose from among reasonable treatment options the agent most likely to produce the best outcome for the individual patient. However, it is important to recognize that there are many caveats to these types of analyses and further study is needed to confirm these results.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A Systematic Literature Review and Network Meta-Analysis
By Thomas B. Casale, Maud Pacou, Laura Mesana, Gaelle Farge, Shawn X. Sun, Mario Castro