Background: Many patients with severe asthma suffer from being overweight or obese, often attributed to unintentional weight gain as side effect of oral corticosteroids (OCS). Anti-interleukin(IL)-5/5Ra biologics can significantly reduce OCS use, but the effect on long-term weight is unknown.

Aims: To examine 1. weight status before and 2 years after anti-IL-5/5Ra initiation, in subgroups based on maintenance OCS use; 2. whether cumulative OCS exposure prior to anti-IL-5/5Ra or changes in cumulative OCS dose is related to weight change.

Methods: Real-world data on weight and cumulative OCS dose from adults included in the Dutch severe asthma registry (RAPSODI) before and up to 2 years after starting anti-IL-5/5Ra were analyzed by linear mixed models and linear regression analyses.

Results: For the included 389 patients (55% female, BMI 28±5 (69%>25) kg/m2, 58% maintenance OCS) mean weight decreased -0.27 kg/year (95%CI -0.51; -0.03, p=0.03), with significant more weight loss in patients with versus without OCS maintenance use (-0.87 kg/year (95%CI -1.21; -0.52, p<0.001) versus +0.54 kg/year  (95%CI 0.26; 0.82, p<0.001), resp., p<0.001. Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years prior anti-IL-5/5Ra initiation (-0.24 kg, 95%CI -0.38; -0.10, p<0.001) and, independently, greater reduction in the cumulative OCS dose during follow-up (-0.27 kg, 95%CI -0.43; -0.11, p<0.001).

Conclusions: Anti-IL-5/5Ra therapy results in modest long-term weight reduction, especially in patients reducing OCS exposure during treatment. Weight is an important outcome for patients and may need consideration during treatment.