title: Retrospective review of combined sirolimus and simvastatin therapy in lymphangioleiomyomatosis.
abstract: BACKGROUND
  Combined simvastatin and sirolimus therapy reduces tuberous sclerosis complex 2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit patients with LAM.
  
  
  METHODS
  To determine whether simvastatin changed the prevalence of adverse events or altered the therapeutic effects of sirolimus, we recorded adverse events and changes in lung function in patients with LAM treated with simvastatin plus sirolimus (n = 14), sirolimus alone (n = 44), or simvastatin alone (n = 20).
  
  
  RESULTS
  Sirolimus-related adverse events in the simvastatin plus sirolimus and sirolimus-only groups were 64% and 66% for stomatitis, 50% and 52% for diarrhea, 50% and 45% for peripheral edema, 36% and 61% for acne, 36% and 30% for hypertension, 29% and 27% for proteinuria, 29% and 27% for leukopenia, and 21% and 27% for hypercholesterolemia. The frequency of simvastatin-related adverse events in the simvastatin-only and simvastatin plus sirolimus groups were 60% and 50% for arthralgias and 35% and 36% for myopathy. Before simvastatin plus sirolimus therapy, FEV1 and diffusing capacity of the lung for carbon monoxide (Dlco) yearly rates of change were, respectively, -1.4 ± 0.2 and -1.8 ± 0.2% predicted. After simvastatin plus sirolimus therapy, these rates changed to +1.2 ± 0.5 (P = .635) and +0.3 ± 0.4% predicted (P = .412), respectively. In 44 patients treated with sirolimus alone, FEV1 and Dlco rates of change were -1.7 ± 0.1 and -2.2 ± 0.1% predicted before treatment and +1.7 ± 0.3 and +0.7 ± 0.3% predicted after treatment (P < .001).
  
  
  CONCLUSIONS
  Therapy with sirolimus and simvastatin does not increase the prevalence of drug adverse events or alter the therapeutic effects of sirolimus.
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.. Electronic address: dasilvaa@nhlbi.nih.gov.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Taveira-DaSilva
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Julien-Williams
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Mario
authors.initials: M
authors.lastname: Stylianou
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D018192:Lymphangioleiomyomatosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D020123:Sirolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D019821:Simvastatin; D020123:Sirolimus