Careful Selection of Patients Is Required to Obtain Higher Potential Benefit From Mepolizumab Therapy

We read with great interest the study of Kavanagh et al1Kavanagh J.E. d'Ancona G. Elstad M. et al.Real-world effectiveness and the characteristics of a 'super-responder' to mepolizumab in severe eosinophilic asthma.Chest. 2020; 158: 491-500Abstract Full Text Full Text PDF Scopus (82) Google Scholar in a previous issue of CHEST (August 2020) on mepolizumab efficacy in a real-world setting or assessment of baseline characteristics associated with response. The authors reported that mepolizumab therapy reduced exacerbation frequency and maintained oral corticosteroid requirements. Nasal polyposis, a lower BMI, and a lower maintained oral corticosteroids requirement at baseline were associated with better outcomes in the severe eosinophilic asthma cohort. We sincerely thank the authors for their substantial contribution to the literature with such a valuable report. We also would like to share our opinions on this study. A few entities caught our attention. First of all, the authors say that “we observed that responders were significantly older, had a higher BMI, and were more likely to have nasal polyposis than nonresponders.” The word higher in this sentence must be lower. Additionally, the authors say that “we are unaware of any further analyses of the utility of other baseline clinical characteristics in predicting response to mepolizumab therapy.” However, there are studies comparing baseline features in response to mepolizumab. In a post hoc analysis, individual patient-level meta-analysis of the MENSA (Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma) and MUSCA (Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control) studies showed that treatment with fixed-dose mepolizumab resulted in similar exacerbation rate reductions and similar improvements in St. George's Respiratory Questionnaire and Asthma Control Questionnaire – 5 scores across all body weight/BMI categories.2Albers F.C. Papi A. Taillé C. et al.Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA.Respir Res. 2019; 20: 169Crossref PubMed Scopus (24) Google Scholar In another study, there was no significant difference in terms of BMI between the mepolizumab responders group and the treatment failure group in severe eosinophilic patients with asthma. The responder groups had higher blood eosinophils and higher nasal polyps. However, ACQ superresponders had a lower baseline BMI.3Harvey E.S. Langton D. Katelaris C. et al.Mepolizumab effectiveness and identification of super-responders in severe asthma.Eur Respir J. 2020; 55: 1902420Crossref Scopus (72) Google Scholar A recent real-life study evaluating clinical efficacy and predictors for treatment response to mepolizumab, baseline characteristics (sex, BMI, smoking history, allergies, baseline level of eosinophils) did not predict treatment response.4Drick N. Seeliger B. Welte T. Fuge J. Suhling H. Anti-IL-5 therapy in patients with severe eosinophilic asthma: clinical efficacy and possible criteria for treatment response.BMC Pulm Med. 2018; 18: 119Crossref PubMed Scopus (68) Google Scholar The last point is that there seems to be a difference in the nasal polyposis rate and previous omalizumab treatment rate between responders and superresponders. Readers would be very grateful if the “P values” were given for comparison of the responders and superresponders in Table 4 because this is a very important comparison. In conclusion, we thank Kavanagh and his colleagues for their contribution to the literature with such an important study. Careful selection of patients is required to achieve the higher potential benefit from mepolizumab therapy, considering the predictive factors. Real-World Effectiveness and the Characteristics of a “Super-Responder” to Mepolizumab in Severe Eosinophilic AsthmaCHESTVol. 158Issue 2PreviewIn a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90% of patients by week 24. Full-Text PDF ResponseCHESTVol. 158Issue 5PreviewWe thank Dr Yilmaz for identifying the error in one of the statements relating to BMI. As discussed in other parts of the manuscript,1 higher BMI was associated with suboptimal response to mepolizumab. Dr Yilmaz references three related publications. The post hoc analysis of MENSA and MUSCA by Albers et al2 examines outcomes in different BMI categories but not in other baseline characteristics of interest, and it does not address whether there were significant differences between BMI groups in their response to mepolizumab, instead only comparing each treated BMI group against overall placebo response. Full-Text PDF