Inhaled Corticosteroids and Sickle Cell Disease Severity in Adults Without Asthma

Importance People living with sickle cell disease (SCD) who have episodic cough and wheeze (ECW) without a diagnosis of asthma have high rates of pain episodes and acute chest syndrome. A previous trial, in which patients with SCD and ECW without asthma received 15 weeks of inhaled mometasone or placebo, showed that inhaled mometasone improved daily pain and reduced soluble vascular cell adhesion molecule 1 (VCAM-1), a marker of disease severity in SCD. Objective To examine the biologic effects and safety of long-term daily inhaled mometasone in patients without asthma but with SCD and ECW. Design, Setting, and Participants This placebo-controlled randomized clinical trial recruited patients with SCD from December 2018 to May 2022. Participants were randomly assigned to receive either inhaled mometasone or placebo for 48 weeks. Data analyses followed the modified intention-to-treat principle and were performed between July and November 2023. Interventions The inhaled mometasone group received 220 μg of inhaled mometasone furoate dry powder once daily. The placebo group received a matching placebo inhaler. Main Outcomes and Measures The primary outcome was percentage change in soluble VCAM-1 levels from baseline to end of study. Secondary outcomes included laboratory results, functional outcomes, patient-reported outcomes, and health care utilization. Results Of the 77 patients who received the intervention and were included in the analysis, 40 were assigned to inhaled mometasone (mean [SD] age, 36.0 [11.6] years; 26 females [65%]) and 37 were assigned to placebo (mean [SD] age, 31.5 [8.6] years; 19 males [51%]). Compared with the placebo group, the inhaled mometasone group increased their soluble VCAM-1 levels by 42% (95% CI, –11% to 96%; P = .02). Point estimates for clinical outcomes favored the placebo group, although the findings were not statistically significant. Conclusions and Relevance In this trial of adults with SCD and ECW, extended courses of inhaled mometasone were associated with worsened markers of disease severity. Inhaled mometasone should not be used long-term in patients with SCD and ECW without a definitive diagnosis of asthma. Trial Registration ClinicalTrials.gov Identifier: NCT03758950