(145) Prescription of Trikafta^TM in Lung Transplant Recipients with Cystic Fibrosis

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

Sunjay R. Devarajan, MD

Assistant Professor
Baylor College of Medicine
Houston, Texas, United States

Co-Author(s)
TB

Tara Barto

United States

JF

Jessica Farrell

Nurse Practitioner
Baylor College of Medicine, United States

CW

Carolyn Wheeler

United States

AO

Angie Osornio

United States

LL

Louisa Lathbridge

United States

CM

Clarissa Morency

Registered Dietitian
Baylor College of Medicine, United States

JE

Julia Estrada

United States

BW

Bethanne Wenger

United States

Background: Trikafta (elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor) received FDA approval in October 2019 for the treatment of cystic fibrosis (CF) in patients ≥ 12 years of age who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Trikafta works by facilitating delivery of functional CFTR protein to the epithelial cell surface and by increasing chloride and bicarbonate movement across the cell membrane, helping to reverse some of the deleterious effects of CF.

The purpose of this study was to develop a protocol for administration and monitoring of Trikafta at Baylor-St Luke's Medical Center in qualifying lung transplant recipients with CF.

Methods: Inclusion criteria

< !-Lung Transplant recipient with diagnosis of CF > 6 months out from lung transplantation

< !-CFTR genotype with at least one F508del allele (genotype documentation required)

< !-Presence of one of the following:

-Chronic sinus disease refractory to non-invasive interventions (irrigation with nasal saline, nasal steroid, intranasal antibiotic washes, etc.) with or without evidence of chronic lung allograft dysfunction

-Underweight with inability to gain weight (BMI target in CF is 22 for females, 23 for male patients)

Exclusion Criteria

< !-Child Pugh Class C liver disease

< !-Active use of azole antifungal therapy (will consider on case-by-case basis)

The BSLMC Lung Transplant team discussed risks and benefits with each eligible patient and arrived at a shared decision whether CFTR modulator treatments would be pursued. If pursued, the Adult CF team would prescribe full or adjusted Trikafta dosing with regular monitoring of weight, liver tests, immunosuppression drug levels, blood glucose, hemoglobin A1c, and routine spirometry. Additionally, one-time baseline and 6 months post-Trikafta assessments of PHQ9, GAD7, SNOT-22, iCAN GI tracker, and CFQ-R would be performed to evaluate for symptomatic and/or well-being improvements.

Results: A total of 8 patients were identified for potential enrollment. Two patients (25%) who enrolled were unable to tolerate the medication due to gastrointestinal side effects and discontinued the medication within days. One patient (12.5%) was unable to get insurance approval for the medication and never initiated therapy. Two patients (25%) experienced new-onset abdominal pain and nausea but opted to continue therapy due to subjective improvements in sinus symptoms, and one of these patients had improvement in their GI symptoms after a dose reduction was made. Statistically, no significant changes were detected in laboratory or symptom assessment scores. Notably, none of the patients required immunosuppression dose adjustment after initiation of Trikafta.

Conclusions: In this small, single-center study looking at treatment effects in post-lung transplant CF patients eligible for triple combination modulator therapy, Trikafta neither significantly improved symptom / well being scores nor routine laboratory testing in this population, including changes to immunosuppression levels and liver enzyme results. A larger, multi-center study will be needed to better understand and characterize the impact of modulator therapies on post-lung transplant recipients with CF.

Acknowledgements: Our team would like to acknowledge Dra. Amparo Sole Jover and Ines Perez for granting us access to the electronic version of the CFQ-R questionnaire.

References:

(145) Prescription of TrikaftaTM in Lung Transplant Recipients with Cystic Fibrosis

Presenting Author(s)

Co-Author(s)

(145) Prescription of Trikafta^TM in Lung Transplant Recipients with Cystic Fibrosis