Combined simvastatin and sirolimus therapy reduce TSC2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit LAM patients.
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 LAM patients treated with simvastatin plus sirolimus (n=14), sirolimus (n=44), or simvastatin (n=20).
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, and simvastatin plus sirolimus groups were 60 and 50 % for arthralgias, and 35 and 36 % for myopathy. Before simvastatin plus sirolimus therapy, FEV1 and 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=0.635) and +0.3±0.4 % predicted, respectively (p=0.412). 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 therapy (p<0.001).
Therapy with sirolimus and simvastatin does not increase the prevalence of drug adverse events or alter the therapeutic effects of sirolimus.