Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis

Respiratory Research

Research

Alessandro Giovanni Fiocchi¹  Fabio Majo¹  Luca Cristiani¹  Francesco Amati²  Stefano Aliberti²  Gianfranco Alicandro³  Andrea Gramegna⁴  Gloria Leonardi⁴  Francesco Blasi⁴  Martina Contarini⁵ 

[1] Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy;Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy;Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy;Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy;

关键词: Weight gain;    Response to treatment;    Personalized medicine;    CFTR modulators;    Elexacaftor;    Overweight;    Adults;   

DOI  :  10.1186/s12931-023-02451-0

 received in 2022-10-04, accepted in 2023-05-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy.MethodsWe conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment’s effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term.ResultsThe mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively.ConclusionsOur results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.

【 授权许可】

CC BY   
© The Author(s) 2023

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