RAPID and RAPID extension trials
• 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.
• 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
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
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
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
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
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