Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience.

Background: Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population.
Methods: Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year.
Results: 132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the F508del variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV ₁ was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV ₁ was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m ² (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was -44.5 mmol/L (95 % CI: -49.8, -39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = -0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common.
Conclusions: ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elsa Fragoso reports a relationship with Vertex Pharmaceuticals Incorporated that includes: speaking and lecture fees. Pilar Azevedo reports a relationship with Vertex Pharmaceuticals Incorporated that includes: consulting or advisory and speaking and lecture fees. Adelina Amorim reports a relationship with Vertex Pharmaceuticals Incorporated that includes: consulting or advisory and speaking and lecture fees. Fernanda Gamboa reports a relationship with Vertex Pharmaceuticals Incorporated that includes: consulting or advisory and speaking and lecture fees. Ana Sofia Santos reports a relationship with Vertex Pharmaceuticals Incorporated that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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