German Registry of AAT Deficiency

The objective of the ongoing German Registry is to obtain information on the efficacy and tolerability of long-term augmentation therapy with Prolastin^® in patients with alpha₁-antitrypsin (AAT) deficiency and pulmonary emphysema on the basis of slowing or arresting the progression of pulmonary emphysema. Periodic reports on this group of patients have been regularly submitted to German healthcare authorities. In 1994, Wencker, et al described 443 subjects recruited into the German Registry who were treated with weekly 60 mg/kg IV Prolastin^®. Sufficient follow-up data (a minimum of baseline and 2 post-bronchodilator forced expiratory volumes at one second [FEV₁] measurements) was available for 287 subjects. The decline in FEV₁ (ΔFEV₁) in these subjects was 57.1 mL/year, with no differences seen between smokers and nonsmokers.¹ This rate of decline was approximately one-half the rate of decline reported for untreated subjects in other studies. Stratified for baseline FEV₁, the ΔFEV₁ was 35.6 mL in 108 subjects with initial FEV₁ <30% predicted and 64 mL in 164 subjects with initial FEV₁ 30% to 65% predicted (P=0.0008).

In another report published in 1997, Seersholm, et al compared the decline in FEV₁ between a cohort of 198 patients from the German Registry receiving Prolastin^® and a group of 97 untreated matched controls from the Danish Registry.² Subjects included in this comparative study were over 25 years of age, ex-smokers, and had results available for 2 or more spirometries at least 1 year apart.

The German Registry subjects had received Prolastin^® for at least 1 year. The investigators diligently attempted to ensure that the 2 groups were comparable, especially in their selection of index cases and ex-smokers, thus ruling out the unpredictable effects of smoking on the change in FEV₁. They also evaluated differences between the two groups in terms of gender, follow-up time, and initial FEV₁, but concluded that these factors did not influence outcome.

Overall, a significantly slower decline of FEV₁ was observed in the treated subjects compared with the untreated group (reduction in ΔFEV₁ = 22 mL/year, P=0.02). Stratification by initial FEV₁% predicted showed the treatment effect only in the group of subjects with an initial FEV₁ of 31% to 65%, in whom the benefit was a reduction in ΔFEV₁ of 21 mL per year. These results are relevant because the majority of patients with AAT deficiency have baseline FEV₁ values in this range when their diagnosis is confirmed.

Weekly Prolastin^® therapy has demonstrated a low occurrence of side effects. In clinical studies with Prolastin^®, reactions were observed in 1.16% of infusions, the most common events being fever (0.77%), lightheadedness (0.19%), and dizziness (0.19%). With any plasma-derived products, the theoretical risk of virus transmission cannot be ruled out. Individuals with selective IgA deficiencies who have known antibodies against IgA should not receive Prolastin^®, since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present. Please see full Prescribing Information.

The efficacy of augmentation therapy was also evaluated in a German multicenter, retrospective cohort study.³ The change in lung function, specifically FEV₁, was analyzed in 96 subjects who had been receiving AAT augmentation therapy. All subjects had a minimum of 2 lung function measurements spaced at least 1 year apart that were obtained before and after beginning augmentation therapy. The majority of patients (88.5%) had PiZ phenotypes and had moderately to severely impaired lung function (FEV₁ <65% of predicted). When grouped according to severity of lung impairment, all subjects experienced a significantly lower decline in FEV₁ during augmentation therapy. When grouped according to severity of lung impairment, this effect was statistically significant only in patients with FEV₁ >65% of predicted. In addition, there was a trend toward statistical significance in patients with FEV₁ between 30% and 65% of predicted. The investigators noted that therapy-associated stabilization of patients with an initial FEV₁ >65% of predicted could potentially reduce the negative impact of AAT deficiency on medical, social, and financial aspects of their lives.

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