Heterogeneity of weight gain after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis

Abstract

Abstract Background. The introduction of the novel therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been showed to be effective in weight gain in both clinical trials and real-world studies. However, this effect appears heterogeneous across patient subgroups and predictors of individual weight gain after treatment are still missing. Methods. This was a multicenter, prospective cohort study enrolling 93 adults with CF at two major CF Centers in Italy. For the pourpose of this study, the cohort was divided into two groups according to median BMI change after 6 months of ETI treatment: ‘responders’ included patients with BMI increase ≥1 kg/m2 and ‘poor responders’ those with BMI increase <1 kg/m2. Results. The median increase in BMI after six months of ETI was 1.0 kg/m2 (0.4-1.7), in line with previous studies. We identified a correlation between BMI increase and both BMI before ETI initiation (r -0.392, P <0.001) and the duration of ETI treatment (r 0.293, P =0.006). BMI responders were more likely to have Phe508del/MF genotype (71% VS. 37%, P = <0.001), younger age at diagnosis (1 [0-4] VS. 5 [0-14] years, P =0.018), pancreatic insufficiency (92% VS. 77%, P =0.042) and CF-related diabetes (49% VS. 21%, P =0.006). Low BMI before ETI initiation (OR 0.75; 95% CI 0.64-0.0.92; P =0.005), pancreatic insufficiency (OR 5.08; 95% CI 1.34-19.28; P =0.017) and the previous use of earlier CFTR modulators (OR 3.41; 95% CI 1.21-9.57; P =0.020) were predictive factors for the status of BMI responder. Conclusions. Our results might help to identify a subset of patients that might deserve both a targeted clinical approach and a translational characterization.