HPE Alpha 1 Antitrypsin Deficiency | Page 17

BOX 2 RAPID and RAPID extension trials RAPID • There was a statistically significant 34% reduction in the annual rate of CT lung density in treated versus placebo patients (0.74g/l/year; p=0.03). • No difference in adverse events rate between treated and placebo groups was observed. RAPID-OLE • Interim analysis demonstrated 36% reduction in the rate of CT lung density loss in patients switched from placebo to therapy. • Delayed start of treatment resulted in irreversible loss of lung tissue. RAPID and RAPID-OLE confirmed the efficacy of a dose of 60mg/kg body weight administered weekly for four years; the clinical effectiveness demonstrated by the slower lung density loss was irrespective of the time at which treatment commenced. time, a disease-modifying effect of therapy in AATD- related pulmonary emphysema; that is, a change in the natural history of disease progression. 12 The importance of early diagnosis and early specific treatment of severe AATD was also demonstrated. 13 Clinical practice In 1987, the US FDA and, subsequently, the respective European agencies approved the use of intravenous AAT therapy, although at that time evidence from randomised clinical trials was lacking. The approval was based on three critical facts: 1. The biochemical efficacy of intravenous preparations to increase the AAT serum above the level considered protective for the lungs (11mM) 2. Safety and well established contraindications 3. Lack of other specific therapy for severe AAT deficiency. AAT therapy is indicated for adult patients with emphysema and documented severe AATD, that is, genotypes PiZZ, PiZ(null), Pi(null,null), PiSZ accompanied by a blood AAT concentration below 11mM. There should be a clinical evidence of respiratory disease progression while on optimal pharmacologic and non-pharmacologic treatment. Respiratory deterioration is most often assessed by lung function testing (FEV1 decline over time). Assessment of impaired exercise capacity in a 6-minute walking test or increased frequency of exacerbations might also prove useful 7–9 (Box 1). It is a general consensus that AAT treatment should be in particular offered to patients with moderate airway obstruction (FEV1 31–65% of predicted). Frequent COPD exacerbations and rapid disease progression defined as decrease of FEV1 >120ml/year are considered other important characteristics 10,11,13 (Box 2). There are no data to support the rationale for AAT therapy in subjects with severe AATD but having no symptoms of respiratory disease; the same is true for the paediatric population. 2 Importantly, there is no evidence to support efficacy of therapy in current smokers, irrespective of their clinical status. 2 The standard dose of AAT is 60mg/kg body weight administered as an intravenous infusion once a week. As demonstrated by trough concentration, it provides a satisfactory level of protein in the blood throughout the week (C trough ~35% of normal). Weekly dosing is considered optimal. There are hospitalpharmacyeurope.com | 2019 | 17