LAUSR

RATIONALE People with obesity often have severe, difficult to control asthma. There is a need to develop better treatments in this population. One potential treatment is roflumilast, a phosphodiesterase 4 inhibitor, as it is reported to have efficacy for treatment of asthma and can promote weight loss. OBJECTIVE to investigate the potential efficacy of roflumilast for the treatment of poorly controlled asthma in people with obesity. METHODS A randomized, double-masked, placebo-controlled trial of 24 weeks of roflumilast versus placebo for the treatment of poorly controlled asthma in people with obesity (body mass index ≥ 30 kg/m2). The primary outcome was change in asthma control test score (ACT). RESULTS Twenty-two people were randomized to roflumilast, 16 to placebo. Roflumilast had no effect on change in ACT (increased by 2.6 [IQR 0.5 to 4.4] in those on roflumilast versus 2.0 [IQR 0.7 to 3.3] in those on placebo). Participants assigned to roflumilast had a 3.5 fold (Relative risk [RR] 95% confidence interval [CI] 1.3 to 9.4) increased risk of an episode of poor asthma control and an 8.1-fold (RR 95% CI 1.01 to 65.0) increased risk of an urgent care visit for asthma. Ten participants (56%) assigned to roflumilast required a course of oral corticosteroids for asthma exacerbations and none in the placebo group. Participants losing ≥ 5% of their body weight experienced a clinically and statistically significant improvement in asthma control (ACT increased by 4.4 [IQR 2.5, 6.3] versus 1.5 [IQR 0.0, 3.0] in those who lost < 5%). CONCLUSIONS Roflumilast had no effect on asthma control. Of concern, roflumilast was associated with an increased risk of exacerbation in in obese individuals with poorly controlled asthma. These results highlight the importance of studying interventions in different sub-populations of people with asthma, particularly people with obesity and asthma who may respond differently to medications than lean people with asthma. Weight loss of at least 5% was associated with improved asthma control indicating that interventions- other than roflumilast -promoting weight loss may have efficacy for treatment of poorly controlled asthma in people with obesity.