Discussion
Our findings show that PwCF have excellent adherence to ETI, but utilization of other CF medications is lower and declines after initiation of highly effective modulator therapy. This finding is consistent with anecdotal experience and a prior small study in PwCF4.The factors underlying reduced utilization of many CF medications likely differ from those that historically influenced medication adherence, since utilization declined even in a subset of PwCF who had excellent adherence prior to starting ETI.
ETI is not a cure for CF, and current guidelines from the US CF Foundation do not recommend stopping other CF specific treatments after starting ETI5. However, findings from the SIMPLIFY study suggest that individuals with relatively preserved lung function could discontinue Dorn or HTS without changes in lung function3, which is consistent with our observations. However, there are several limitations that could influence our analysis. We were not able to control for factors such as declining chest physiotherapy use, which could influence changes in lung function. Furthermore, we cannot rule out the possibility that evaluation of more individuals over a longer time frame might reveal relationships that were not observed in our study. Ongoing decline in ppFEV1 in PwCF on ETI has not been observed in other studies6, and we speculate that this is a short term phenomenon reflecting changes in routines and will stabilize with time. The discrepancy with prior studies could reflect factors unique to our center or differences between real world retrospective data and follow-up data of a clinical trial population.
A decrease in PERT utilization was not expected since the initial clinical trials have not suggested that ETI improves pancreatic function. Reduced use of pancreatic enzymes could also reflect ETI related improvements in other aspects of GI physiology, resulting in better absorption even with less enzyme replacement.
Another limitation is that this single institution study may not be representative of the CF population as a whole. Also, MPR may overestimate actual medication utilization as PwCF continue to fill medications that they are not actually using. However, MPR has the advantage that it can be readily assessed in a large population and may reveal patterns difficult to measure is a more targeted group.