Abstract 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
Inoue et al. (Fri,) studied this question.