Abstract Rational In the natural course of lymphangioleiomyomatosis (LAM), patients experience progressive loss of lung function. After treatment with sirolimus, there is significant heterogeneity in lung function response among individuals. Differentiation of lung function response trajectories under sirolimus treatment is valuable for accurately identifying response phenotypes and providing information for the clinical trials of new therapies. Methods Based on the LAM cohort of Peking Union Medical College Hospital, a group-based trajectory modeling (GBTM) cohort dataset was derived. LAM patients with sirolimus treatment records and at least two pulmonary function tests at and after the treatment were included, while patients who discontinued medication for more than 6 months or had never undergone monitoring of sirolimus blood concentration were excluded from the analysis. GBTM was used to model the change from baseline in forced expiratory volume in one second (FEV1) at different follow-up time points, and to identify different FEV1 change trajectories after sirolimus treatment. Multiple logistic regression analysis was used to explore the influencing factors of different trajectory groups. Results The GBTM analysis included 183 LAM patients. The FEV1 change trajectories after sirolimus treatment in LAM patients were classified into three categories: significantly improved, stable, and continuously declined, with the stable group accounting for an estimated proportion of 68%, the continuously declined group 20.7%, and the significantly improved group 11.3%. Using the continuously declined group as a reference, we found that baseline FVC% of predicted value were significantly associated with the improved group (compare with FVC 100% of predicted value, 80%-100% of predicted value, OR = 13.0, 95%CI 1.5-115.1,P=0.022; 80% of predicted value, OR = 31.6, 95%CI 2.93-341.6,P=0.005) and stable group (compare with FVC 100% of predicted value, 80% of predicted value, OR = 4.9, 95%CI 1.5-16.3,P=0.010). Conclusion The trajectories of FEV1 change from baseline after sirolimus treatment in LAM patients can be classified into three categories: significantly improved (11.3%), stable (68%), and continuously declined (20.7%). Compared with the continuously declined group, patients in the stable and significantly improved groups were associated with lower baseline FVC% of predicted value. This abstract is funded by: National High Level Hospital Clinical Research Funding (2022-PUMCH-B-107)
Xu et al. (Fri,) studied this question.