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.