Incidence of transaminitis in adults with cystic fibrosis taking elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator modulators are a cornerstone of CF treatment. However, many patients develop CF liver disease (CFLD) over time, and previous data indicate a risk for transaminase elevation with modulator use. Elexacaftor/tezacaftor/ivacaftor is a commonly prescribed modulator with broad efficacy among CF genomic profiles. Theoretically, elexacaftor/tezacaftor/ivacaftor drug-induced liver injury could exacerbate and further worsen CFLD, but holding modulators can cause a decline in clinical status. OBJECTIVES: This study was designed to determine the real-world incidence of transaminase elevations in adult patients with CF taking elexacaftor/tezacaftor/ivacaftor. METHODS: This exploratory, retrospective descriptive study included all adults with CF-prescribed elexacaftor/tezacaftor/ivacaftor at our institution's outpatient CF clinic. We explored transaminase elevations in 2 separate outcomes: incidence of transaminase elevations of more than 3 times the upper limit of normal (ULN), and transaminase elevations of 25% or more above baseline. RESULTS: 83 patients were prescribed elexacaftor/tezacaftor/ivacaftor. Nine patients (11%) experienced an elevation of more than 3 times ULN and 62 (75%) experienced an elevation of 25% or more above baseline. The median days to transaminase elevation were 108 and 135 days, respectively. Therapy was not discontinued due to transaminase elevations in any of the patients. CONCLUSION: Transaminase elevations among adults taking elexacaftor/tezacaftor/ivacaftor were common but did not result in discontinuation of therapy. Pharmacists should be reassured of the liver safety profile of this important medication for patients with CF.

Mental status changes during elexacaftor/tezacaftor / ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta) is the newest Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drug approved by the Food and Drug Administration. Post-marketing reports with earlier CFTR modulators suggest these medications can impact mood, and in clinical trials an adverse effect of headache was reported with all currently approved CFTR modulators. However, there are no other documented reports of mental status changes during clinical trials or in post-marketing reports with elexacaftor/tezacaftor/ivacaftor. In this case series, we describe 6 patients who reported "mental fogginess" or other mental status changes shortly after initiation of this drug. The mechanism of this patient-reported side effect is still unclear. All patients noticed a change within the first 3 months of therapy. The management differed in each case, with all four cystic fibrosis (CF) care teams utilizing a patient-centered decision-making approach to address this concern.