Background: Elexacaftor/tezacaftor/ivacaftor (Trikafta) is a triple therapy modulator used for treating patients with cystic fibrosis (CF) since late 2019. The medication was recently approved in June 2021 for clinical use in children 6 to 11 years of age. Clinical trials on elexacaftor/tezacaftor/ivacaftor have reported skin rash as one of the commonly observed side effects of the medication. The rash is reported to be mild to moderate in severity and self-resolving in most cases. Clinical trials have also reported that the rash is more commonly seen in younger children (24% in 6 to 11 years of age) and children and adults with a single delta F508 mutation [1-3].

Methods: A retrospective chart review was conducted in all pediatric patients 6 years and older with CF who were prescribed elexacaftor/tezacaftor/ivacaftor between October 2019 and April 2022. Patients were excluded if they were started on this triple therapy agent from an outside institution or never started therapy. The primary endpoint was the occurrence of rash. The age, gender, genotype, and the incidence of rash were compared between the younger (6 to 11 years, n=14) and older (more than 12 years, n=22) age group. Data analysis included descriptive statistics and chi-square.

Results: 39 total patients were prescribed elexacaftor/tezacaftor/ivacaftor between the study period and 36 were included in the study. Two patients were excluded because they never started the triple therapy agent, and one patient was excluded because they started elexacaftor/tezacaftor/ivacaftor from an outside cystic fibrosis center. The rash was observed in 28.6% of younger children compared to 9% in older children (p = 0.54). Of the six total children that had the rash, four were with a single delta F508 mutation. A total of four children required interruption of therapy and one child had a recurring rash after the medication was restarted (picture attached). The rash was described as mildly pruritic, erythematous, maculopapular rash mostly observed on the back, abdomen, and extremities, sparing palms, soles, and face.

Conclusions: We have noted higher incidence of rash in younger children and higher percentage of rash in children with a single delta F508, which is similar to the observation in clinical trials. Even though one patient presented with recurrent rash, all patients eventually experienced resolution of rash. The pathophysiology of the rash with this triple therapy modulator remains unclear.

Acknowledgements:

I would like to acknowledge and thank Dr.’s Kiran Nandalike, Sanjay Jhawar, Rory Kamerman-Kretzmer, and Yi Shi for their contributions and assistance with reviewing the abstract.

References: [1] Middleton PG, Mall MA, Dřevínek P, Lands LC, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381(19):1809-1819. https://doi.org/10.1056/NEJMoa1908639

[2] Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940-1948. https://doi.org/10.1016/S0140-6736(19)32597-8

[3] Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, et al. A phase 3 open-label study of elexacaftor/tezacaftor/ivacaftor in children 6 through 11 years of age with cystic fibrosis and at least one F508del allele. Am J Respir Crit Care Med. 2021;203(12):1522-1532. doi: https://doi.org/10.1164/rccm.202102-0509OC