Predicting weight gain in patients with cystic fibrosis on triple combination modulator

• DOI: 10.1002/ppul.26982
• Publication Date: 2024-04-12T13:24:06Z
• Authors: Kelly L. Stewart; Rhonda Szczesniak; Theodore G. Liou
• Keywords: Male; Adult; Indoles; Cystic Fibrosis; Pyridines; Cystic Fibrosis Transmembrane Conductance Regulator; Middle Aged; Quinolones; Weight Gain; Aminophenols; Body Mass Index; Young Adult; Drug Combinations; 03 medical and health sciences; 0302 clinical medicine; Humans; Pyrazoles; Female; Pyrroles; Longitudinal Studies; Benzodioxoles; Aged

AbstractBackgroundCystic fibrosis (CF) is caused by CF transmembrane conductance regulator (CFTR) gene mutations producing dysfunctional CFTR proteins leading to progressive clinical disease. Elexacaftor‐tezacaftor‐ivacaftor (ETI) remarkably improves lung disease but is associated with substantial weight gain.Study Design and MethodsWe performed a single‐center longitudinal study predicting 6‐month weight gain after ETI initiation. We used linear mixed effects modeling (LME) to determine association of ETI treatment with changing body mass index (BMI). Using linear regression, we examined BMI prediction models with distinct combinations of main effects to identify a model useful for patient counseling. We used up to eight commonly observed clinical characteristics as input variables (age, sex, percent predicted FEV1 [FEV1%], F508del homozygous state, pancreatic sufficiency, HgbA1c, prior modulator use and prior year number of pulmonary exacerbations).ResultsWe evaluated 154 patients (19‐73 years old, 54% female, FEV1% = 19−121, 0−6 prior year pulmonary exacerbations). LME demonstrated an association between ETI use and weight increases. Exhaustive testing suggested a parsimonious linear regression model well‐fitted to data that is potentially useful for counseling. The two variable model shows that on average, BMI decreases by 0.045 (95% Confidence Interval [CI] = −0.069 to −0.021, p < 0.001) for every year of age and increases by 0.322 (CI = 0.142 to 0.502, p = 0.001) for each additional prior year exacerbation at the time of ETI initiation.InterpretationYoung patients with many prior year pulmonary exacerbations likely have the largest 6 month weight gain after starting ETI.