In cystic fibrosis patients, elexacaftor/tezacaftor/ivacaftor (ETI) offered substantial clinical improvements in terms of lung function, respiratory symptoms, and body mass index in a diverse population naïve to modulator drug therapy, utilizing existing two-drug combinations, or utilizing ivacaftor alone, according to the findings of a post-approval real-world study.

This prospective, observational study (PROMISE) aimed to explore the broad effects of ETI (cystic fibrosis modulator drug) through thirty months of clinical use in a more diverse patient population with planned evaluations following six months. The study recruited 487 people with cystic fibrosis (age ≥12 years) with ≥1 F508del allele and commencing ETI for the 1^st time.

Evaluations were carried out before and one, three, and six months during ETI therapy. The endpoints incorporated alteration in percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index, sweat chloride concentration, and self-reported respiratory symptoms. The average age of recruited participants was 25.1 years. At baseline, 44.1% of participants were on tezacaftor/ivacaftor or lumacaftor/ivacaftor and  6.7% of participants were on ivacaftor alone, consistent with F508del homozygosity and G551D allele, respectively.

At six months into ETI therapy, an improvement in ppFEV1 (9.76 percentage points from the baseline), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain score (20.4 points from the baseline) was noted. Each group also reported a profound decrease in sweat chloride concentration (-41.7 mmol/L from the baseline), that correlated with improved ppFEV1 in the overall study population. Also, there was a considerable rise in body mass index.

Alterations were larger in those naïve to modulators but significant in all groups, including those managed with ivacaftor at the baseline. Thus, substantial improvements in clinical outcomes were noted with ETI use in patients suffering from cystic fibrosis.