Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma – a systematic review and meta-analysis

Abstract

Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging.Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma.Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab.Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to –0.94 annual exacerbations (95% CI –1.08;–0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low.Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome.Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

Cost-effectiveness and comparative effectiveness of biologic therapy for asthma

“…12e14 A comparison of mepolizumab and reslizumab found no significant difference in any of the predefined clinical outcomes, including forced expiratory volume in 1 second (FEV 1 ), ACQ, AQLQ, annual exacerbations, and serious adverse events. 12 The authors noted that the quality of evidence was very low concerning interdrug difference comparison because there was substantial variability among the studies, including key differences in asthma severity and blood eosinophil level cutoffs. 12 The mepolizumab studies included patients with severe asthma based on GINA guidelines and an eosinophil cutoff of 150 to 300/mL, 12 whereas the reslizumab studies included patients with moderate asthma per GINA guidelines and an eosinophil cutoff of 400/mL.…”

“…12 The authors noted that the quality of evidence was very low concerning interdrug difference comparison because there was substantial variability among the studies, including key differences in asthma severity and blood eosinophil level cutoffs. 12 The mepolizumab studies included patients with severe asthma based on GINA guidelines and an eosinophil cutoff of 150 to 300/mL, 12 whereas the reslizumab studies included patients with moderate asthma per GINA guidelines and an eosinophil cutoff of 400/mL. 12 Unlike the aforementioned study, a separate network metaanalysis controlled for the heterogeneity between benralizumab and reslizumab studies by only selecting a benralizumab subgroup with a blood eosinophil count of 300/mL and a reslizumab subgroup with GINA step 4/5 or 2 previous exacerbations and an eosinophil count of 400/mL.…”

“…12 The mepolizumab studies included patients with severe asthma based on GINA guidelines and an eosinophil cutoff of 150 to 300/mL, 12 whereas the reslizumab studies included patients with moderate asthma per GINA guidelines and an eosinophil cutoff of 400/mL. 12 Unlike the aforementioned study, a separate network metaanalysis controlled for the heterogeneity between benralizumab and reslizumab studies by only selecting a benralizumab subgroup with a blood eosinophil count of 300/mL and a reslizumab subgroup with GINA step 4/5 or 2 previous exacerbations and an eosinophil count of 400/mL. 13 Reslizumab was found to significantly improve ACQ and AQLQ scores compared with benralizumab administered every 4 weeks, but the magnitude of these changes did not meet the minimal important difference.…”

Eosinophilic Phenotype: The Lesson from Research Models to Severe Asthma

“…On one hand, this means that these therapeutic strategies may not be sufficient to reverse remodeling changes of severe asthma even if mepolizumab has been shown to decrease the deposition of tenascin, lumican and collagen III in the basal membrane of mild atopic asthmatics as well as the degree of TGF-β in the bronchoalveolar lavage fluid [43]. Accordingly, lung function was not expected to be positively modified by anti-IL-5 treatments in severe asthma and a meta-analysis of nine randomized, placebo-controlled, clinical trials including mepolizumab or reslizumab reported a mild absolute difference of FEV1 in favor of the anti-IL-5 treatment compared to placebo [84].…”

Selection of Biologics in Severe Asthma: A Multifaceted Algorithm

“…A recent systematic review and meta-analysis revealed no differences between mepolizumab and reslizumab in terms of efficacy or safety measures 33 .…”