Up to 73% of patients with severe asthma have overlapping allergic and eosinophilic endophenotypes and are eligible for treatment with anti-eosinophilic (e.g., mepolizumab) or anti-IgE (omalizumab) biologics. We assessed mepolizumab real-world effectiveness in patients with severe asthma and overlapping endophenotypes based on omalizumab treatment eligibility. The 2-year, international, prospective, REALITI-A study enrolled adults with asthma and a physician decision to initiate mepolizumab (100mg subcutaneously). This post hoc analysis, using data from the full study population at 1 year, assessed the rate of clinically significant exacerbations (CSEs; requiring systemic corticosteroids and/or emergency room visit/hospitalization) and maintenance oral corticosteroid (mOCS) dose pre- and 1-year following mepolizumab. Outcomes were stratified by omalizumab eligibility (eligible/ineligible, based on total immunoglobulin E [tIgE]/atopy/weight; EU/Japan criteria). A subset of 540 patients (of 822 treated patients) had sufficient data to assess omalizumab eligibility, with 349 (65%) eligible and 191 (35%) ineligible; 150 (43%) omalizumab eligible patients had previously received omalizumab treatment. Omalizumab eligible versus ineligible patients had higher geometric mean (SD log) baseline blood eosinophil counts (cells/μL: 352[1.235] vs 303[1.282]) and higher geometric mean (SD log) baseline tIgE (KU/L: 213[1.08] vs 131[2.48]). Following mepolizumab, the rate of CSEs (rate ratio [95% CI]) decreased regardless of omalizumab eligibility (eligible: 0.29 [0.25, 0.34]; ineligible: 0.32[0.27,0.38]). At Week 53–56, median (IQR) mOCS dose (mg/day) decreased versus baseline, regardless of omalizumab eligibility (eligible: 3.3[0.0,6.5] vs 10.0[5.0,15.0]; ineligible: 1.9[0.0, 7.5] vs 10.0[5.0,14.7]). Real-world mepolizumab treatment reduced CSEs and mOCS use in patients with severe eosinophilic asthma, irrespective of omalizumab eligibility.

Introduction: Mepolizumab (MEPO) improves lung function in clinical trials but patient selection for these studies is restricted. No restrictions apply in standard clinical practice, and data from real-life settings is limited. Aims: To evaluate the effectiveness of MEPO in improving lung function in real-life settings. Methods: REALITI-A enrolled patients with severe eosinophilic asthma (SEA) who initiated MEPO from 51 centers in 7 countries. FEV1 was measured by standard spirometry during routine clinic visits. Baseline FEV1 was defined as the latest measure prior to MEPO initiation. Post-initiation FEV1 were averages of FEV1 measures for each subject during the prospective observation periods. Changes from baseline were evaluated using mixed model repeated measures. FEV1 changes were also evaluated by baseline blood eosinophil counts (BEC). Results: FEV1 data was available from 298 and 174 patients at baseline and 9-12 months. Baseline FEV1 least square (LS) mean (95% CI) was 2.0L (1.9-2.1). FEV1 mean changes (95% CI) from baseline at 0-3, 3-6, 6-9 and 9-12 months were respectively 92.5 ml (38.1–147.0), 88.9 ml (29.2-148.6), 89.9 ml (24.4–155.4) and 123.3 ml (56.5–190.0). Significant increases were evident in subjects with BEC≥300 cells/µL (n=238), with a LS mean increase (95% CI) of 128.3 ml (25.7-231.0) at 9-12 months from baseline; sample size for subgroups with lower BEC is too small to draw meaningful conclusions. Conclusions: SEA patients, treated with MEPO in real life settings, demonstrated improvement in lung function that was sustained across the year of observation. This improvement was evident in those with baseline BEC of ≥300 cells/µL. Funding: GSK [204710]