STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life.

ABSTRACT

BACKGROUND: Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of 'false-negative' T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits. METHODS: The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17-75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal. DISCUSSION: This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020-07-06, https//www.trialregister.nl/trial/8759 . Protocol version and date version 2.1, 20 November 2020.