Changes in Provider Practices for the Management of Cystic Fibrosis (CF) in the Era of Highly Effective Modulator Therapy

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Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which result in thickened airway mucus, chronic infection, and bronchiectasis. Many daily therapies are recommended by the CF Foundation (CFF) to treat these complications, including inhaled hypertonic saline, dornase alfa, and antibiotics, oral azithromycin, and airway clearance therapies. Historically, adherence to these therapies is quite low, as they are exceedingly time consuming, requiring up to 2-4 hours to complete daily. Persons with CF also have acute worsening of symptoms, called pulmonary exacerbations (PEx), that are treated with systemic antibiotics and are associated with progressive lung function decline and increased mortality. CFTR modulators aim to reverse CFTR dysfunction. With the approval of the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI), 90% of the CF population is eligible for highly effective modulator therapy (HEMT), defined as CFTR modulator therapy resulting in a substantial increase in percent predicted FEV1 and improvement in sweat chloride concentrations. Prior to the approval of ETI, only ~5% of patients were eligible for therapy with HEMT. Our local data show that a majority of patients on ETI report that they have simplified their chronic therapy regimens following discussion with their CF providers, given the burden associated with these therapies and improvement in symptoms they experienced after starting ETI. Likewise, providers at our CF center report prescribing oral antibiotics in the home setting for the treatment of PEx rather than intravenous (IV) antibiotics in the hospital more frequently for patients on ETI. The details of how national practice patterns have changed with regards to chronic maintenance therapies and management of PEx since the approval of ETI remains uncertain. We hypothesize that providers have modified the management of both chronic and acute therapies for CF such that the approach to CF is less aggressive, requiring fewer chronic medications and less burdensome treatments for PEx. This current study will: (1) utilize a national survey to evaluate CF provider practice patterns, assessing if providers continue to follow guidelines for chronic and acute therapies in patients on ETI. If modifications were made, we will assess what chronic therapies were modified and changes in the frequency of oral and IV antibiotic use and hospitalizations for the management of PEx in patients on ETI; (2) evaluate the management of PEx prospectively at our center to determine if the proportion of oral vs. IV antibiotics and treatment in the home vs. hospital setting has changed since the approval of ETI. The results of this proposal address an important question regarding the evolving management of CF in the era of HEMT and have direct implications for the clinical care of persons with CF. If our results suggest that provider practices have changed since the approval of ETI, further research is necessary to determine if these changes are associated with worsened clinical outcomes and updates should be made to clinical care guidelines accordingly.