(195) The impact of elexacaftor/tezacaftor/ivacaftor (Trikafta) on serum markers of fat-soluble vitamin levels in people with cystic fibrosis

Background: The advent of highly effective modulator therapy (HEMT), including ivacaftor (Kalydeco) and elexacaftor/tezacaftor/ivacaftor (Trikafta, ELX/TEZ/IVA), has revolutionized the care of most people with cystic fibrosis (PwCF). Less is known about the effectiveness of HEMT in treating extra-pulmonary manifestations, including vitamin malabsorption. The purpose of this study is to evaluate the impact of ELX/TEZ/IVA on serum markers of fat-soluble vitamin levels, specifically Vitamins A, D, E, and prothrombin time (PT, a marker for Vitamin K), among PwCF ≥12 years of age followed at two large CF centers (one pediatric and one adult) in Seattle, WA. This abstract describes the results for the pediatric participants.

Methods: In this retrospective cohort study, participants age 12 and older on ELX/TEZ/IVA were identified through chart review, and data on demographics, medications, co-morbidities, and vitamin levels were collected. ELX/TEZ/IVA start date was obtained from clinic progress notes. The two years pre ELX/TEZ/IVA initiation and up to 2 years post initiation were used for determining the proportion of participants with one or more vitamin levels in the supratherapeutic or subtherapeutic range. Comparisons of proportions were performed with McNemar’s Chi-squared test. A two-sided test p-value less than 0.05 was considered statistically significant, and all analyses were completed in R version 4.1.2.

Results: Seventy two participants met inclusion criteria for enrollment, and 54 (75%) had follow-up vitamin levels after ELX/TEZ/IVA was started. The median age at ELX/TEZ/IVA initiation was 15.93 years [13.48-17.81], 61% were homozygous for F508del, 54% were male, and 88% were Caucasian. The median baseline BMI was 20.84 kg/m² [18.82-22.64], and the median baseline FEV1 % predicted was 101 [93-110]. There were no significant differences in median Vitamin A, Vitamin D or PT levels before and after ELX/TEZ/IVA initiation (see Table 1). The median Vitamin E level decreased from 8.8 to 6.7mg/L (p< 0.005). The percentage of participants with subtherapeutic Vitamin D levels decreased from 80% to 63% following ELX/TEZ/IVA initiation (p=0.007), and the percentage with elevated PT levels decreased from 20% to 7% (p=0.046). There was no significant difference in the proportion of participants with subtherapeutic Vitamin A or E levels. There were no measured Vitamin A, D or E levels in the supratherapeutic range following ELX/TEZ/IVA initiation.

Conclusions: Our results demonstrate an improved proportion of participants with Vitamin D and PT within the normal range following ELX/TEZ/IVA initiation. By contrast, the median Vitamin E level decreased significantly, and there was no significant change in Vitamin A levels. Reassuringly, there were no Vitamin A, D or E levels in the supratherapeutic range after ELX/TEZ/IVA. There are several possible explanations for our results. Firstly, while it was assumed that participants continued vitamin supplementation following ELX/TEZ/IVA initiation, we were unable to verify this assumption. It is possible that as participants’ health improved on ELX/TEZ/IVA, they may have elected to stop taking vitamin supplementation. We continue to investigate how vitamin intake has changed post-ELX/TEZ/IVA. Alternatively, increased exposure to sunlight and/or dietary changes could have contributed to our findings. Data collection and analysis at the second study site are ongoing and may help clarify these relationships.

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