Discussion
Elexacaftor/tezacaftor/ivacaftor, the newest CFTR modulator, is efficacious as demonstrated by improved ppFEV1, decreased respiratory symptoms and acute pulmonary exacerbation rates in patients with CF. However, use has not been well established in those with liver disease requiring transplantation. This case series describes the use of elx/tez/iva in ten individuals with CF post-liver transplantation, across six CF centers. This report found that introducing elx/tez/iva, in patients post-liver transplant, regardless of indication for transplant, was safe and showed a clinical benefit.
Elz/tez/iva was well tolerated by patients and the most common adverse events reported were elevations in LFTs. Trends in LFT elevations were mild and stabilized after a couple weeks of therapy. One patient discontinued therapy due to transaminitis, with a documented AST and ALT of 6 times the ULN. Other possible safety concerns were fatigue, stool frequency changes, and seizure.
In the presence of a known PGP drug interaction, this case series highlighted that with close monitoring of the immunosuppressive regimen, elx/tez/iva can be introduced. The most common starting dose was 200 mg/100 mg/150 mg of elx/tez/iva, respectively. For those initiated at a reduced dose, dose escalation was performed based on LFT monitoring. For patients on tacrolimus, trough concentrations did fluctuate leading to dose adjustment in five (55.6%) patients. Two patients reported tacrolimus toxicity with one patient discontinuing elx/tez/iva. This patient was started on full dose elx/tez/iva, which may suggest that initiation at lower doses with a slow titration may reduce the degree of fluctuation with trough concentrations and toxicity. Experience from these patients suggest that tacrolimus toxicity may be avoided with close monitoring early in elx/tez/iva therapy initiation. There was one patient on sirolimus that required a dose decrease, but this was most likely due to discontinuation of the CYP450 inducer, lum/iva. Refer to Table 2 for complete information on immunosuppression regimens.
Although use of this medication was only observed short-term, there was noticeable clinical improvement measured; for specific information refer to Table 3. Overall, this case series suggests that those with CFLD may experience clinical benefit with minimal adverse events.