Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics

Abstract

Background: The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response.

Methods: This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders-i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George's Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction).

Results: Of the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index.

Conclusions: After switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics. Trial registration This manuscript is a post hoc analysis of data from the OSMO study. ClinicalTrials.gov, NCT02654145. Registered January 13, 2016.

Keywords: Asthma; Asthma treatment; Biologics; Eosinophils.

Conflict of interest statement

SGS, JA, DM, and RGP are all employees of GSK and hold stocks/shares in GSK. FCA is a former employee of GSK and holds GSK stocks/shares and is currently employed by Avillion US, Inc. DVG is a former employee of GSK and holds GSK stock/shares and is currently employed by Chiesi USA; KRC has received consulting fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, GSK, Grifols, Kamada, Novartis, Roche, and Sanofi Regeneron; has undertaken research funded by Amgen, AstraZeneca, Boehringer Ingelheim, CSL Behring, GSK, Grifols, Kamada, Novartis, Roche and Sanofi; has participated in continuing medical education activities sponsored in whole or in part by AstraZeneca, Boehringer Ingelheim, GSK, Grifols, Novartis and Teva. KRC is also participating in research funded by the Canadian Institutes of Health Research. GD has received personal fees or research grants from Novartis Pharma, AstraZeneca, GSK, Boehringer Ingelheim, Mundi Pharma, Vivisol, Sanofi, Chiesi, ALK, Teva, MSD and AGIR à Dom; has participated in CME activities sponsored by GSK, AstraZeneca, Novartis Pharma, Chiesi, MSD, Takeda, AGIR à Dom, Orkyn, Mundi Pharma, ALK, Stallergenes, Boehringer Ingelheim and Teva; is participating in research funded by GSK, ALK, AstraZeneca, Novartis Pharma, Boehringer Ingelheim, Vitalair, AB science, Amgen, Lilly, Sanofi, Roche and Teva. MB has received personal fees or research grants from AstraZeneca, Novartis, GSK, Boehringer Ingelheim, and Sanofi. MCL has participated in advisory board meetings for GSK, Gossamer Bio and AstraZeneca, and has received research grants from GSK, and Gossamer Bio. BC is an advisor for, has received consultancy fees from, and is on the speaker's bureau AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron and Sanofi-Genzyme. XM has received fees as a speaker, scientific advisor or participant of clinical studies for AstraZeneca, Boehringer Ingelheim, Chiesi, Faes, GSK, Menarini, MundiPharma, Novartis and Teva.

Figures

Fig. 1

Proportion of efficacy outcome responders* for ACQ-5 score, SGRQ total score, pre-bronchodilator FEV1, and exacerbations. *Responders were defined as: ACQ-5 score improvement from baseline of ≥ 0.5-points at Week 32; SGRQ total score improvement from baseline of ≥ 4 points at Week 32; pre-bronchodilator FEV1 improvement from baseline of ≥ 100 mL at Week 32; ≥ 50% reduction in the annualised rate of clinically significant exacerbations during the study treatment period versus the previous year; patients who discontinued mepolizumab treatment but remained within the study (n = 2) were considered non-responders in this analysis. ACQ-5 Asthma Control Questionnaire-5, FEV1 forced expiratory volume in 1s, SGRQ St George’s Respiratory Questionnaire

Fig. 2

Efficacy of switching to mepolizumab from omalizumab by blood eosinophil count thresholds at baseline. *Pre-treatment refers to the 12 months prior to screening; †32-week study period refers to the time between first dose of mepolizumab and study conclusion, regardless of treatment discontinuation. Rate ratio reflecting annualised clinically significant exacerbation rate during 32-week study period compared with rate during pre-treatment period; MCID for ACQ-5 and SGRQ is 0.5 points and 4 points, respectively; error bars represent SE. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1s, LS least squares, MCID minimum clinically important difference, RR rate ratio, SE standard error, SGRQ St George's Respiratory Questionnaire

Fig. 3

Efficacy of switching to mepolizumab from omalizumab by prior treatment regimen and omalizumab treatment duration. *Pre-treatment refers to the 12 months prior to screening; †32-week study period refers to the time between first dose of mepolizumab and study conclusion, regardless of treatment discontinuation. Rate ratio reflecting annualised clinically significant exacerbation rate during 32-week study period compared with rate during pre-treatment period. MCID for ACQ-5 and SGRQ is 0.5 points and 4 points, respectively; error bars represent SE. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1s, LS least squares, MCID minimum clinically important difference, RR rate ratio, SE standard error, SGRQ St. George's Respiratory Questionnaire

Fig. 4

Efficacy of switching to mepolizumab from omalizumab by the presence or absence of comorbidities. *Pre-treatment refers to the 12 months prior to screening; †32-week study period refers to the time between first dose of mepolizumab and study conclusion, regardless of treatment discontinuation. Rate ratio reflecting annualised clinically significant exacerbation rate during 32-week study period compared with rate during pre-treatment period. MCID for ACQ-5 and SGRQ is 0.5 points and 4 points, respectively; error bars represent SE. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1s, GERD gastroesophageal reflux disease, LS least squares, MCID minimum clinically important difference, NP nasal polyps, NSAID aspirin/non-steroidal anti-inflammatory drug, RR rate ratio, SE standard error, SGRQ St George's Respiratory Questionnaire

Fig. 5

Efficacy of switching to mepolizumab from omalizumab by exacerbation history and maintenance OCS use. *Pre-treatment refers to the 12 months prior to screening; †32-week study period refers to the time between first dose of mepolizumab and study conclusion, regardless of treatment discontinuation. Rate ratio reflecting annualised clinically significant exacerbation rate during 32-week study period compared with rate during pre-treatment period. MCID for ACQ-5 and SGRQ is 0.5 points and 4 points, respectively; error bars represent SE. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1s, LS least squares, MCID minimum clinically important difference, OCS oral corticosteroid, RR rate ratio, SE standard error, SGRQ St George's Respiratory Questionnaire