Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis

doi:10.1056/NEJMoa1100391

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N Engl J Med. Author manuscript; available in PMC 2011 Oct 28.

Published in final edited form as:

N Engl J Med. 2011 Apr 28; 364(17): 1595–1606.

Published online 2011 Mar 16. doi: 10.1056/NEJMoa1100391

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Table 2

Effects of Sirolimus on Primary and Selected Secondary Outcome Variables during the Treatment Period.^*

Variable	Value at 12 Months		Change from Baseline			Rate of Change per Month
Variable	Placebo (N = 34)	Sirolimus (N = 41)	Placebo (N = 34)	Sirolimus (N = 41)	P Value^†	Placebo (N = 43)	Sirolimus (N = 46)	P Value^‡
Pulmonary function
FEV₁ (ml)	1272±414	1383±394	−134±182^§	19±124	<0.001	−12±2^¶	1±2	<0.001

FVC (ml)	2843±668	2780±735	−129±233^§	97±260	0.001	−11±3^¶	8±3^¶	<0.001

Total lung capacity (ml)	5464±1217	4944±982	−7±650	94±504	0.65	−2±7	8±7	0.34

Residual volume (ml)	2502±969	2112±617	−16 ±514	38±538	0.61	−3±7	4±7	0.46

Functional residual capacity (ml)	3260±968	2912±660	−123±521	53±335	0.43	−11±6	6±6	0.049

DL_CO (ml/mm Hg/min)	9.61±4.06	9.62±3.92	−0.62±2.89^§	−0.06±1.50	0.38	−0.06±0.03^¶	−0.01±0.02	0.17

6-Minute walk distance (m)	418±107	431±104	26±51^§	24±59^§	0.99	1.47±0.87	1.65±0.81^¶	0.88

Score on EuroQOL visual-analogue scale for quality of life^\|\|	65.60±18.47^**	73.71±18.03	−2.34±15.77	6.10±16.96	0.02	−0.21±0.20	0.39±0.19^¶	0.03

Total score on Functional Performance Inventory^††	2.33±0.47	2.35±0.49	−0.05±0.24	0.10±0.38	0.08	−0.009±0.004^¶	0.005±0.004	0.03

Serum VEGF-D (pg/ml)	2444±3862^**	862±540	−14.81±1113	−1032±1301^§	0.001	−2.42±17.23	−88.01±16.61^¶	0.001

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^*Plus–minus values are means ±SD. DL_CO denotes diffusing capacity for carbon monoxide, FEV₁ forced expiratory volume in 1 second, FVC forced vital capacity, and VEGF-D vascular endothelial growth factor D.

^†Two-sided P values for the comparison between the placebo and sirolimus groups of the mean change from baseline were calculated with the use of a general linear model, with adjustment for baseline levels of variables.

^‡Two-sided P values for the comparison between the placebo and sirolimus groups of the rate of change per month were calculated with the use of a linear mixed-effects model.

^§The two-sided P value for the change from baseline within the placebo or sirolimus group, as calculated with the use of the Wilcoxon signed-rank test, was less than 0.05 for FVC and 6-minute walk distance, less than 0.01 for DL_CO, and less than 0.001 for FEV₁ and VEGF-D level.

^¶The two-sided P value for the rate of change per month within the placebo or sirolimus group, as calculated with the use of a linear mixed-effects model, was less than 0.05 for the total score of the Functional Performance Inventory, the DL_CO, and the EuroQOL visual-analogue scale, less than 0.01 for the FVC, and less than 0.001 for VEGF-D level and FEV₁.

^||The EuroQOL visual-analogue scale measures self-reported ratings of health status. Scores range from 0 to 100, with lower scores indicating worse functioning.

^**The two-sided P value for the difference between the placebo and sirolimus groups at 12 months was less than 0.05, as calculated with the use of the Wilcoxon rank-sum test.

^††Scores on the Functional Performance Inventory range from 1 to 4, with lower scores indicating lower health status.