Long-term effectiveness of dual CFTR modulator treatment of Cystic Fibrosis

Abstract

<b>Background:</b> Although short-term efficacy of lumacaftor/ivacaftor and tezacaftor/ivacaftor is clearly established in randomized trials, data on long-term effectiveness is limited. <b>Aim:</b> This registry-based cohort study assessed longitudinal outcomes of F508del-homozygous people with CF aged 12 years and older, up to 3 years after the introduction of the dual Cystic Fibrosis transmembrane conductancance regulator (CFTR) modulators. <b>Methods:</b> Annual data (2010-2019) were retrieved from the Dutch Cystic Fibrosis Registry. Longitudinal trends in percent predicted forced expiratory volume in 1s (ppFEV1) decline, body mass index (BMI), BMI Z-score and intravenous antibiotic treatment duration before and after CFTR modulator initiation were assessed with linear and negative binomial mixed models. <b>Results:</b> We included 401 participants. ppFEV1 decline improved from -0.88%/year to -0.33%/year after modulator initiation (change:0.55%/year, CI:0.04–1.07, p=0.037). In adults, annual BMI trend was not altered (change:0.10 kg/m²/year, CI:-0.01–0.20, p=0.085). Annual BMI Z-score in children reversed from -0.05/year before modulator treatment to 0.09/year afterwards (change:0.14/year, CI:0.06–0.22, p&lt;0.001). Intravenous antibiotic treatment duration showed a three-fold reduction in the first year after modulator initiation (IRR:0.28, CI:0.19–0.40, p&lt;0.001), but the annual trend did not change in subsequent years (IRR:1.15, CI:0.92–1.46, p=0.231). <b>Conclusion:</b> Long-term ppFEV1 decline improved after the introduction of LUM/IVA and TEZ/IVA, which was also observed for BMI Z-score in children, but not BMI in adults.&nbsp;Intravenous antibiotic use was reduced in the first year after modulator initiation, but increased in subsequent years.