Résumé
Objective: Patients (F508del/F508del or F508del/MF) with severe CF (ppFEV1<40%) were not represented in the Phase 3 VX445 (Kaftrio®) [Table presented] clinical trials. We aimed to assess real-world efficacy, safety and tolerability in this cohort. Method: All patients with severe lung 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 (Table 1). After adjusting for time, there was a relative reduction of 68.89% IV and 21.43% PO antibiotic usage as well as a 66.9% reduction in hospital bed days. Improvements in CFQR-R and D domains and FACIT fatigue scores were observed. Patient 4 developed an erythematous diffuse rash on day 7 which resolved with antihistamines. No liver function abnormalities have been seen to date. 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%).