(219) Changes in BMI to FEV1 correlation post-elexacaftor/tezacaftor/ivacaftor therapy

Background: In cystic fibrosis patients, higher body mass index (BMI) is directly correlated with improved lung function. Studies have shown that patients taking highly effective modulators experience a significant increase in FEV1, as well as improvement in BMI. However, it is unknown whether this increase in BMI is sustained long term and if the positive correlation between BMI and FEV1 remains the same or plateaus.

Methods: Pediatric patients who had at least one BMI percentile (%ile) value two years prior and 2 years post -elexacaftor/tezacaftor/ivacaftor initiation were included in this retrospective study. The average BMI %iles and percent predicted FEV1 (ppFEV1) over both time frames were calculated and compared. Data were analyzed using descriptive and comparative statistics, and correlation was analyzed by linear regression.

Results: A total of 98 patients were included; 50% were male, 90.8% Caucasian, and 61.2% were F508del/F508del. The mean age at the start of elexacaftor/tezacaftor/ivacaftor was 13.4±3.8 years. Mean BMI %ile two years pre-initiation and two years post-initiation were 46.54 ± 25.33 and 51.69 ± 27.78 (p=0.001), respectively. Mean ppFEV1 two years pre-initiation and two years post-initiation were 88.86 ± 18.86 and 97.16±17.94 (p < 0.001). Knowing that when BMI %iles are greater than 70%, the positive correlation between BMI and ppFEV1 declines, we reanalyzed a subset of patients who had a pre-therapy BMI < 70%ile (n = 78). Additionally, since changes in BMI occur gradually, we assessed BMI to ppFEV1 correlation from baseline to two different time frames, 0-1 year post-initiation and 1-2 years post-initiation. Mean baseline and 2 year post-therapy ppFEV1 in this cohort was 91.03%±17.03 and 98.44%±17.51, respectively. Mean BMI %ile at baseline was 37.05±18.56 and the correlation coefficient to ppFEV1 was 0.559. In aggregate, mean BMI %ile 0-2 years post-initiation was 43.31±24.58 and r=0.366. Mean BMI %ile from 0-1 years post-therapy was 43.46±24.45 and r=0.427; mean BMI %ile from 1-2 years post-therapy was 45.11±26.16 and r=0.307. Differences in ppFEV1 to BMI %ile correlations showed a trend towards statistical significance (p=0.07) comparing all pre and post treatment data, and differences in correlations were statistically significant (p=0.023) comparing pre-treatment to 1-2 year post-treatment (Figure 1).

Conclusions: Highly effective modulator therapy concurrently improves ppFEV1 and BMI %ile in pediatric patients with CF, and improvements in BMI %ile appear to remain sustained over two years. However, the positive correlation between BMI and pulmonary function declines with time post therapy, suggesting a potential plateau effect. In the era of highly effective modulators, the impact of increasing BMI and obesity on overall CF care and lung function continues to be a question of interest and requires additional careful study.

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