|Title:||COMPASSIONATE USE TRIPLE THERAPY CFTR MODULATION (KAFTRIO) IN SEVERE DISEASE. SINGLE-CENTRE REAL WORLD CLINICAL OUTCOMES, SAFETY AND TOLERABILITY|
|Author(s):||D. Morrissy Y. McCarthy M. McCarthy J. Dorgan C. Fleming C. Howlett S. Twohig D. Murphy J. Eustace B. Plant|
|Institution:||Cork Centre for Cystic Fibrosis, Cork University Hospital|
|Poster:||Click to view poster|
|Category:||CF and Pulmonary Infections|
|Abstract:||Objective: Patients (DelF508/DelF508 or DelF508/MF) with severe lung disease (ppFEV1<40%) were not represented in the Phase 3 VX445 (Kaftrio) clinical trials. We aimed to assess real-world efficacy, safety, tolerability and the role of novel biomarkers in this cohort.|
Method: All patients with severe disease (ppFEV1<40%) attending our clinic eligible for Vertex’s managed-access-programme who received treatment were assessed prospectively at 3 monthly intervals.
Results: 7 of 8 patients remain on therapy. Irrespective of prior CFTR modulator therapy, notable improvements were observed (See Table). A relative reduction in IV (68.89%) and hospital days (66.9%), as well as Improvements in CFQR-R and D domains and FACIT(fatigue) scores were observed.
Genotype: F/F (delF508/delF508), F/MF (delF508/Minimal Function). Transitioned from *Orkambi or **Symkevi. +Transient Rash
CT imaging (Bhalla-scoring-system) demonstrated statistically significant improvements in “Total Bhalla Score”, “Peribronchial Thickening” and “Mucus Plugging”. Additionally plasma cytokines IL-6 and IL-1B significantly reduced.
Patient 4 developed an erythematous diffuse rash (day 7) which resolved with antihistamines. Patient 6 died while on therapy due to multimorbidities including Pulmonary Embolism (Covid PCR and antibody negative), Persistent Pneumothorax and sepsis.
Conclusion: This cohort demonstrates preliminary clinically meaningful real-world efficacy, safety and tolerability for patients (F/F, F/MF) with severe disease (ppFEV1<40%) as well as highlighting clinical utility of CT imaging and cytokine measurement as potential biomarkers.