INHALED mometasone was associated with increased markers of disease severity in adults with sickle cell disease (SCD) without a diagnosis of asthma, according to a randomised clinical trial investigating the effects of long-term treatment over 48 weeks. The findings raised concerns about the safety of extended inhaled corticosteroid use in this patient population.
People with SCD who experience episodic cough and wheeze (ECW) without asthma have previously demonstrated high rates of pain episodes and acute chest syndrome. Previous research found that 15 weeks of inhaled mometasone improved daily pain and reduced soluble vascular cell adhesion molecule 1 (VCAM-1), a marker of disease severity. However, the longer-term biological effects and safety of treatment remained unclear.
The placebo-controlled randomised clinical trial recruited adults with SCD between December 2018 and May 2022. A total of 77 participants were included in the analysis, with 40 assigned to receive inhaled mometasone and 37 assigned to placebo.
Participants in the treatment group received 220 μg of inhaled mometasone furoate dry powder once daily, while the control group received a matching placebo inhaler. Both interventions continued for 48 weeks.
The primary outcome was the percentage change in soluble VCAM-1 levels from baseline to the end of the study. Secondary outcomes included laboratory measurements, functional assessments, patient-reported outcomes, and healthcare utilisation.
Compared with placebo, inhaled mometasone was associated with a 42% increase in soluble VCAM-1 levels (95% confidence interval: −11% to 96%; p=0.02). This suggested that prolonged treatment may negatively affect biological markers associated with SCD severity.
Furthermore, point estimates for clinical outcomes generally favoured the placebo group, although these differences did not reach statistical significance.
The findings highlighted a potential safety concern regarding prolonged inhaled corticosteroid treatment in adults with SCD and ECW without a confirmed asthma diagnosis.
The researchers concluded that extended courses of inhaled mometasone were associated with worsening markers of disease severity. They advised against long-term use in patients with SCD and ECW without a definitive asthma diagnosis.
These results also highlighted the importance of establishing an accurate asthma diagnosis before initiating long-term inhaled corticosteroid treatment in adults with SCD, particularly given the potential implications for disease severity.
Reference
Curtis SA et al. Inhaled corticosteroids and sickle cell disease severity in adults without asthma: a randomized clinical trial. JAMA Netw Open. 2026;9;(11):e2642232.
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