Vol.:(0123456789) 1 3 Lung (2019) 197:107–109 https://doi.org/10.1007/s00408-018-0185-8 LETTER TO THE EDITOR Iftikhar and Colleagues Reply: Methodology Clarifed Imran H. Iftikhar 1  · Mathew Schimmel 1  · William Bender 1  · Colin Swenson 1  · David Amrol 2 Received: 21 November 2018 / Accepted: 26 November 2018 / Published online: 5 December 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 We thank Gunsoy and colleagues for their comments on our paper [1] and appreciate the opportunity to further clarify our methods and results. The defnitions of asthma exac- erbations difered in diferent studies and was provided in each article mostly in their ‘methods’ sections. Yes, it is true, that we ‘did not extract treatment efects’ directly from the source articles. We simply used the asthma exac- erbation data reported in each study (see Table for further clarifcation) in our meta-analysis. We never reported that some biologics increased asthma exacerbations as Gunsoy et al. imply. It is true that ‘patient-years’ were not provided in each study, which is why we specifed in the methods section, that we calculated the patient-years based on the data on follow-up provided in each study. However, it is not true, that exacerbation rates were not reported ‘within most studies’ (see Table). For Chupp et al. [2], Bel et al. [3], and Castro et al. [4] studies, the asthma exacerbation ‘counts’/ rates/percentages (defnitions and reporting formats of which varied) were reported in the respective papers (see Table). Our intent for using the approach of calculating ‘person years’ was to present the data in a uniform format across a range of diferent studies that difered in their follow-up periods. However, it is understandable how this may have misled some of the readers. We take this opportunity to pre- sent the results in the conventional format using just the counts of asthma exacerbations from individual papers (this time, however, excluding Nair [5], Pavord [6], and Hanania [7] studies to avoid any further confusions on calculation of asthma exacerbation counts), and simply calculating odds ratios. The results (see Table) confrm that dupilumab and reslizumab were least associated with asthma exacerbations, and show similar results for mepolizumab. However, these results just like the results of the analysis reported in our original paper have important limitations: (1) only stud- ies from which these data were extractable in a common format were included and others were excluded, (2) since these results are not a ‘network’ meta-analysis of asthma exacerbations, they do not provide ‘indirect estimates’ of ‘between-drug’ comparisons, and (3) since the time when we analyzed the results, two new much awaited studies [8, 9] on dupilumab have been published. With regards to the latter, an updated network meta-analysis is necessary at this time, since in ours, we only included two of the dupilumab studies. Study ID Drug events (%) Placebo events (%) ‘Asthma exacerbation’ in source articles Benralizumab studies  Nowalk 2014 43 47 Subjects with ≥ 1 asthma exacerbation, n (%)—week 24 Table 2 Pg. 18  Park 2016 9 8 Reported as “serious adverse event” Page 141 text  Bleecker 2016 13 19 “Worsening asthma” (during “the treatment period”) Pg 2124 3rd para  FitzGerald 2016 4 5 “Worsening asthma” (during “on-treatment period”) Pg 2138, para 3  Ferguson 2017 1 2 AE (“worsening asthma” in > 3% pf patients) Pg 573, 2nd para Pooled odds ratio: 0.80 (0.54–1.19), p = 0.28 Reslizumab studies  Castro 2011 8 19 “Clinical asthma exac- erbation” Pg 1129, 2nd para * Imran H. Iftikhar imran.hasan.iftikhar@emory.edu 1 Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University School of Medicine, 613 Michael St, NE, Atlanta, GA, USA 2 Division of Allergy and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA