On 2015 Sep 30, Peter Gøtzsche commented:

Augmentation therapy with alpha-1 antitrypsin cannot be recommended

Chapman et al. published the third trial of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency.1 The new trial adds very little, if anything, to the results of the two previous trials, which we have summarised in our Cochrane review.2 In the Cochrane review, the decline in lung density measured by CT scan was slightly less on drug than on placebo, difference 1.14 g/l (95% confidence interval 0.14 to 2.14). This minute effect is about the same when the new trial is added to the analysis, difference 0.86 (0.31 to 1.42). The effect of drug on FEV1 was the opposite as that on lung density. In the Cochrane review, FEV1 declined slightly faster on drug than on placebo, difference 20 ml per year (-41 to 1; p = 0.06). Adding the new trial doesn’t change this estimate much, standardised mean difference -0.19 (-0.42 to 0.05). In the accompanying editorial,3 Crystal writes that there is now “evidence of clinical efficacy” and suggests that augmentation treatment should be used earlier than at present, despite the fact that the treatment costs far more than most people earn in a year before taxes. An effect on a surrogate marker is not “evidence of clinical efficacy” and we therefore don’t reimburse or use this treatment in Denmark. We conclude in our Cochrane review: “Augmentation therapy with alpha-1 antitrypsin cannot be recommended, in view of the lack of evidence of clinical benefit and the cost of treatment.”2

1 Chapman KR, Burdon JG, Piitulainen E, et al. ntravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015;386:360-8.

2 Gøtzsche PC, Johansen HK. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. Cochrane Database Syst Rev 2010;(7):CD007851.

3 Crystal RG. Augmentation treatment for α1 antitrypsin defi ciency. Lancet 2015;386:319-20.

On 2015 Sep 30, Peter Gøtzsche commented:

Augmentation therapy with alpha-1 antitrypsin cannot be recommended

Chapman et al. published the third trial of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency.1 The new trial adds very little, if anything, to the results of the two previous trials, which we have summarised in our Cochrane review.2 In the Cochrane review, the decline in lung density measured by CT scan was slightly less on drug than on placebo, difference 1.14 g/l (95% confidence interval 0.14 to 2.14). This minute effect is about the same when the new trial is added to the analysis, difference 0.86 (0.31 to 1.42). The effect of drug on FEV1 was the opposite as that on lung density. In the Cochrane review, FEV1 declined slightly faster on drug than on placebo, difference 20 ml per year (-41 to 1; p = 0.06). Adding the new trial doesn’t change this estimate much, standardised mean difference -0.19 (-0.42 to 0.05). In the accompanying editorial,3 Crystal writes that there is now “evidence of clinical efficacy” and suggests that augmentation treatment should be used earlier than at present, despite the fact that the treatment costs far more than most people earn in a year before taxes. An effect on a surrogate marker is not “evidence of clinical efficacy” and we therefore don’t reimburse or use this treatment in Denmark. We conclude in our Cochrane review: “Augmentation therapy with alpha-1 antitrypsin cannot be recommended, in view of the lack of evidence of clinical benefit and the cost of treatment.”2

1 Chapman KR, Burdon JG, Piitulainen E, et al. ntravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015;386:360-8.

2 Gøtzsche PC, Johansen HK. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. Cochrane Database Syst Rev 2010;(7):CD007851.

3 Crystal RG. Augmentation treatment for α1 antitrypsin defi ciency. Lancet 2015;386:319-20.