(49) Medication Adherence and Lung Function Changes with Elexacaftor/Tezacaftor/Ivacaftor Treatment

Background: Introduction of triple combination therapy (TCT) with elexacaftor/tezacaftor/ivacaftor improves clinical measures in many people with CF (PwCF). Anecdotally, many PwCF respond to improved clinical status by reducing adherence to routine CF care including inhaled medications. However, the extent to which this occurs and clinical consequences of reduced adherence are unknown.

Methods: To address this question, we identified all PwCF on CFTR modulator therapy from our pharmacy database. Medication adherence measured by medication possession ratio (actual months filled/prescribed months) for modulators and the inhaled medications hypertonic saline (HTS) and dornase alpha were assessed and compared to clinical outcome measures.

Results: A total of 311 PwCF had 3 or more CFTR modulator prescriptions filled over the time frame analyzed (Nov 2016 – Aug 2021), of whom 235 had 3 or more fills for TCT. Medication adherence was high across all modulators (0.99±0.10 for Iva alone, 0.98±0.09 for lumacaftor/Iva, 0.97±0.11 for Tez/Iva, 1.02±0.20 for TCT). Lung function values were available for 156 PwCF before and after TCT initiation, demonstrating the expected increase in percent predicted FEV1 values with treatment (76.2±24.6 vs. 84.1±24.8, p< 0.003). However, rate of change in FEV1 per year remained negative post modulator, with trend towards more negative slope after treatment initiation (-0.7±5.1 vs. -1.5±6.1, p=0.15). Adherence to HTS and dornase also declined post TCT initiation within the group as a whole (negative slope in medication possession ratio with time) and was most evident among those who regularly filled these prescriptions through our pharmacy (n=46, 37 respectively), in whom adherence was >80% and steady over time pre TCT, but fell to 69% and 73% respectively with a negative slope over time post TCT (Figure). Adherence to pancreatic enzymes (n=52) followed a similar pattern. However, changes in adherence to HTS or dornase after modulator therapy were not associated with lung function or changes in lung function over time.

Conclusions: In this real world study, PwCF on TCT were strongly adherent to modulator therapy, with substantial gains in lung function but continued decline in lung function over time. While continued lung function decline on TCT could reflect the observed decreased in adherence to inhaled CF therapies, we did not observe a direct correlation between lung function and adherence. Further study will be needed to determine if declines in lung function post TCT are sustained or reflect short-term changes in approach to CF care with highly effective modulator treatment.

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