Replies to post #98387 on Biotech Values

[genisi]

Re: Researchers Say Drugs for AAT Deficiency Are Useless

I have read the review by Gotzsche and Johansen and here are a few points I would note:

They only looked at 2 studies that were not powered to show statsig efficacy, were quite different (even AAT dose was not the standard), had many dropouts in the placebo groups, they mainly looked at FEV1, which is not the best endpoint in the disease and doesn't reflect loss of lung tissue, and did not report mortality data (mortality is a very important outcome in this disease). So, while I agree that clinical trials with proper end points are needed to demonstrate efficacy of AAT augmentation therapy in alfa-1 antitrypsin deficiency, I certainly object to the authors' conclusion that the treatment is usless.

[genisi]

Analysis of data from 2 trials shows clinical effectiveness of AAT augmentation therapy:

Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry


http://respiratory-research.com/content/11/1/136

Robert A Stockley et al. Published: 5 October 2010

Background

Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT) augmentation therapy on emphysema progression using CT densitometry.
Methods

Data from these similar trials, a 2-center Danish-Dutch study (n = 54) and the 3-center EXAcerbations and CT scan as Lung Endpoints (EXACTLE) study (n = 65), were pooled to increase the statistical power. The change in 15th percentile of lung density (PD15) measured by CT scan was obtained from both trials. All subjects had 1 CT scan at baseline and at least 1 CT scan after treatment. Densitometric data from 119 patients (AAT [Alfalastin or Prolastin], n = 60; placebo, n = 59) were analysed by a statistical/endpoint analysis method. To adjust for lung volume, volume correction was made by including the change in log-transformed total lung volume as a covariate in the statistical model.
Results

Mean follow-up was approximately 2.5 years. The mean change in lung density from baseline to last CT scan was -4.082 g/L for AAT and -6.379 g/L for placebo with a treatment difference of 2.297 (95% CI, 0.669 to 3.926; p = 0.006). The corresponding annual declines were -1.73 and -2.74 g/L/yr, respectively.
Conclusions

The overall results of the combined analysis of 2 separate trials of comparable design, and the only 2 controlled clinical trials completed to date, has confirmed that IV AAT augmentation therapy significantly reduces the decline in lung density and may therefore reduce the future risk of mortality in patients with AAT deficiency-related emphysema. Trial registration: The EXACTLE study was registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML