A39-14 Effects of Low Dose Sirolimus on Health-Related Quality Of Life (HR-QOL) in Patients With Lymphangioleiomyomatosis (LAM)

Rationale LAM is a rare, systemic and intractable disease characterized by cystic changes of lungs, abdominal tumors, and pleural/peritoneal effusions. Sirolimus is recommended to use to suppress mTOR activity, which is generally initiated at 2mg/day, according to trough level. However, recent reports suggested the efficacy of lower dose treatments. There is still controversy about the optimal dose. We conducted a prospective study in which sirolimus was started (after baselineevaluation; BL) from 1mg/day for 24 weeks (V5) to sirolimus naive LAM patients and dose was escalated to 2mg/day until 48 weeks (V9). FEV1(primary endpoint) and several secondary endpoints significantly improved at V5 (p < 0.05), but less improvement between V5 and V9 (Figure, left). Patients reported fewer adverse events under 1 mg/day than 2 mg/day (Inoue et al. ATS 2025). This report is the results of the pre-defined secondary outcomes, patient oriented HR-QOL data. Methods 48 LAM patients diagnosed in NHO Kinki Chuo Chest Medical Center (Osaka, Japan) {47 sporadic and one tuberous sclerosis complex, 42(37-49) year old, median (25%-75%), all female} were prospectively enrolled. The protocol was approved in our IRB, and informed consents were obtained from all patients. Predefined primary endpoint (FEV1), and secondary endpoints (%DLco, serum VEGF-D, etc., and HR-QOLs {COPD Assessment Test (CAT), Japanese version of the Kupperman Menopausal Index (KKSI), St. George’s Respiratory Questionnaire (SGRQ), MOS 36-Item Short-Form Health Survey (SF-36)} were analyzed at BL, V5, and V9. Results [HR-QOL and other measures at BL] There were following significant correlation between HR-QOLs and other outcomes (p < 0.05); CAT score vs FEV1, %DLco, and VEGF-D; KKSI score vs age, menopause, and VEGF-D; SGRQ Symptom score vs FEV1, %DLco, and VEGF-D; SGRQ Activity score vs FEV1, %DLco, and VEGF-D; SGRQ Impact score vs FEV1, %DLco, and VEGF-D; SGRQ Total score vs FEV1, %DLco, and VEGF-D; SF36 PF score vs FEV1, %DLco, and VEGF-D; SF36 RP score vs FEV1, %DLco, and VEGF-D; SF36 MH score VEGF-D. [Effects of sirolimus on HR-QOL] Patients reported significant improvement about the following HR-QOL questionnaires. CAT score at BL vs V5; SGRQ SYMPTOM at BL vs V5 and V9 (Figure right); SGRQ ACTIVITY at BL vs V5; SGRQ TOTAL at BL vs V9; SF-36 PF at BL vs V5; SF-36 SF at BL and V5; SF-36 RE at BL vs V5. Conclusions These patient-reported HR-QOLs questionnaires were sensitive and useful outcomes for LAM managements. Low dose (1mg/day) sirolimus treatment might be satisfactory and acceptable from patient-side. This abstract is funded by: partially with the grant from JMHLW