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Table 1 Characteristics of included studies in the systematic review and meta-analysis

From: The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis

Author, Publication Year, Country Journal Study design No of patientsa Study duration Intervention and sample size Study outcomes Lung function inclusion criteria
Bissler[11], 2008, USA N Engl J Med single-center prospective open-label phase 1–2 trial 25 (6/12/7) treatment 1 year, observation 1 year Sirolimus (n = 25) Renal AMLs, lung function, 6MWD, lung-cyst volume, AEs and neurologic assessment. NA
Davies [21], 2011, UK Clin Cancer Res multicenter prospective nonrandomized open label phase 2 trial 16 (6/3/7) treatment 2 years Sirolimus (n = 16) Renal AMLs, lung function, AEs and neurocognitive function. NA
McCormack [14], 2011, USA N Engl J Med multi-center, randomized, placebo-controlled study (MILES) 89 (81/8/0) treatment 1 year, obervation 1 year sirolimus group (n = 46); placebo group (n = 43) Lung function, 6MWD, VEGF-D levels and QOL scores and AEs. FEV1 ≤ 70%
Dabora [22], 2011,USA PLoS ONE multicenter, open label, single arm, phase 2 trail 36 (0/21/15) treatment 1 year sirolimus (n = 36) Renal AMLs, lung function, brain tumors and liver AMLs, skin lesions, VEGF-D levels, AEs. NA
Bissler [13],2013, USA Lancet multicenter randomized, double-blind, placebo-controlled, phase 3 study (EXIST-2) 118 (5/24/89) median everolimus 38 weeks (10–85 weeks) everolimus group (n = 79); placebo group (n = 39) AMLs, skin lesion, pulmonary function, VEGF-D levels, everolimus pharmacokinetics and AEs. DLCO > 35%
Budde [20], 2015, USA Brit J Clin Pharmaco multicenter randomized, double-blind, placebo-controlled, phase 3 study (EXIST-2) 79 (2/20/57) median everolimus 38 weeks (10–85 weeks) everolimus(n = 79) Associations between everolimus concentration and AMLs size, VEGF-D and other biomarker levels. DLCO > 35%
Goldberg [17], 2015, USA Eur Respir J multicenter, open-label, nonrandomised, phase 2 trial 24 (19/5/0) 26 weeks everolimus, (n = 24) AEs, everolimus pharmacokinetics, VEGF-D levels, lung function. (30% ≤ FEV1 ≤ 80%) or (30% ≤ FEV1 ≤ 90% and DLCO < 80%)
Takada [23], 2016, Japan Annals ATS mulcenter single arm, open-label trial (MLSTS) 63b 2-year study period Sirolimus (n = 63) AEs, lung function and QOL scores. NA
Bee [24], 2017, UK Thorax a prospective national cohort study, single arm 47 (38/9/0) 35.8 ± 18 months Sirolimus (n = 47) Lung function, AEs. NA
  1. AMLs angiomyolipomas, AEs adverse events, DLCO diffusing capacity for carbon monoxide, FEV1 forced expiratory volume in 1 s, LAM lymphangioleiomyomatosis, QOL quality of life, TSC tuberous sclerosis complex, VEGF-D vascular endothelial growth factor D, RV residual volume, 6MWD 6-min walking distance
  2. a represent the number of subjects with the diagnosis of sporadic LAM(sLAM), TSC-LAM, and only TSC without LAM manifestation
  3. bLAM patients were included in the study, no accurate data on the number of sLAM or TSC-LAM