Search

Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day prednisolone boost (0.5 mg/kg). High-dose OCS reduced median blood eosinophils (−60 cells/µl; 95% CI −140 to 10), periostin (−8.4 ng/mL; −11.6 to –2.8), FeNO (−19.0 ppb; −28.5 to –4.0), IL-5 (−0.17 pg/mL; −0.28 to –0.08) and IL-13 (−0.15 pg/mL; −0.27 to –0.03). There were small improvements in mean FEV1 (0.16 L; 0.05 to 0.27) and (Asthma Control Questionnaire) ACQ-7 score (0.3; 0.0 to 0.7). Study measures returned to baseline 1-month postintervention. Following rescue OCS, 1 month is sufficient before using type-2 biomarkers to guide long-term treatment.Trial registration numberNCT01948401.

Introduction and objectives Epidemiologic studies have implicated aeroallergens and respiratory infections as triggers underlying seasonal increases in asthma exacerbations in spring and autumn months. These seasonal factors may trigger or amplify airway inflammation in atopic, Type 2 high asthma patients that precipitates acute worsening of symptoms. Biologic therapies targeting Type 2 cytokine pathways have demonstrated efficacy in reducing the rate of severe asthma exacerbations, particularly in patients selected on the basis of Type 2 biomarkers. In children with asthma, increased inhaled corticosteroid or anti-IgE therapy has been found to reduce the rate of seasonal exacerbations. We hypothesised that lebrikizumab (anti-IL-13) therapy would likewise be effective in reducing seasonal exacerbations in adults with asthma. Methods We conducted post-hoc analyses of the Phase III LAVOLTA studies (NCT01867125 and NCT01868061) to assess the seasonal dependence of exacerbations and efficacy of lebrikizumab in 2,148 adults with moderate to severe asthma. We employed Poisson regression utilising linear mixed models to estimate the per-month (normalised by hemisphere) annualised exacerbation rate and treatment effect of lebrikizumab in reducing exacerbations (percent rate reduction). Results Per-month exacerbation rates in placebo treated eosinophil-low ( Conclusions We conclude that seasonal spikes in exacerbations may be primarily dependent on Type 2 inflammatory processes. The molecular pathways underlying asthma exacerbations are heterogeneous and therapeutic strategies targeting Type 2 biology alone may have the greatest efficacy in limiting seasonal spikes in exacerbation rates. Overall, these data highlight that a significant proportion of asthma exacerbations may be independent of seasonal influences and/or Type 2 biology and that increased therapeutic efficacy may require targeting multiple distinct pathways in asthma.