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Rationale: Mepolizumab (Mepo) is indicated as add-on therapy for patients with severe asthma and is effective at reducing exacerbations. This post-hoc analysis aims to quantify the impact of Mepo on Work Productivity and Activity Impairment – General Health (WPAI-GH) in two clinical trials (MENSA, SIRIUS). Methods: The WPAI-GH questionnaire is a validated instrument and was administered at baseline and each 4-weekly visit. Responses were analysed using mixed model repeated measures. Results: 50% (MENSA, 285/576) and 49% (SIRIUS, 66/135) of patients were employed at baseline. Employed patients were younger and more likely to be male compared to unemployed patients, but had similar asthma disease characteristics. Mepo treatment improved WPAI-GH versus placebo patients receiving optimized standard of care (Figure 1). Conclusions: Mepo had a considerable beneficial impact on work and activity impairment in both studies; however, differences in SIRIUS and %work time missed due to health in MENSA were not significant, likely due to small number of patients in SIRIUS and few work hours reported as missed in MENSA. These results suggest that Mepo may have indirect cost benefits to employers and society by allowing patients to increase productivity. Funding: GSK [115588/NCT01691521 & 115575/NCT01691508]