no data to confirm effectiveness of individualised
treatment based on trough levels. In some
circumstances, regimens with higher doses
administered over longer time intervals are used
in some European centres; for example, double dose,
bi-weekly (Box 3).
Infusion is usually given over a period of 15
minutes. First doses should be administered under
the supervision of a healthcare professional with
experience in this treatment. Self-administration
in the home setting seems to be a viable option for
some patients, but data are limited. 14
Safety and contraindications to therapy
Treatment is considered safe as demonstrated by
real-life practice and similar adverse event rates
between treated and placebo groups in clinical
studies. 8,10,11 There are no specific side effects; the
most frequently observed were headache and
dizziness. The reported safety of a bi-weekly infusion
regimen was similar to once weekly. 15
The main contraindications to intravenous
supplementation of AAT are hypersensitivity and
IgA deficiency. Risk of hypersensitivity to the active
substance or any other excipient should always be
considered, including in patients who have tolerated
well previous infusions. In patients with suspected
allergic or anaphylactic reactions, in particular
those with tachycardia, hypotension, confusion,
syncope and pharyngeal oedema, the need for
immediate discontinuation of infusion and medical
intervention should be considered.
IgA-deficient patients presenting anti-IgA
antibodies are at risk of severe life-threatening
hypersensitivity reactions. IgA deficiency is one
of the most frequent immunodeficiency disorders
and should be excluded prior to first AAT infusion.
An IgA serum level of <15mg/l is considered
diagnostic.
There are additional important considerations
prior to instigating therapy:
• Therapy should be carefully considered in subjects
with a history of allergic, anaphylactic or severe
generalised reactions to plasma-derived products
• Treatment is life-long. The patient should therefore
be well informed and any reasonable suspicions that
the requirements of weekly intravenous infusions
might not be met should be taken into account.
• Current smoking is generally considered an
important contraindication because tobacco
smoke is a driving factor for the development
and progression of AATD-related emphysema.
The patient is expected to cease smoking at
least six months before the first infusion. While
on treatment, testing for cotinine (a nicotine
metabolite) in urine or blood can be performed to
ensure the patient’s adherence to non-smoking
References
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2 Miravitlles M et al. European
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18 | 2019 | hospitalpharmacyeurope.com
BOX 3
Treatment of AATD-related
emphysema
• Intravenous infusion is the only available disease-
specific therapy. It slows progression of emphysema
as determined by lung CT density decline (0.79g/l/
year versus placebo; p=0.002).
• Pharmacologic and non-pharmacologic treatment
of lung disease should be optimised according to
current guidelines.
• Lung transplant is a viable option for AATD
patients; it significantly improves quality of life
although survival benefit is not clear.
• In decompensated chronic heart disease, and
chronic or acute accompanying COPD exacerbations,
intravenous infusion might further deteriorate the
symptoms of right ventricular failure.
Weekly
intravenous
infusions of AAT
protein purified
from healthy
donors’ blood
supplemented
protein level and
activity in
peripheral blood
and epithelial
lining fluid
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J Respir Crit Care Med
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8 Dirksen A et al. Exploring
the role of CT densitometry:
a randomised study of
augmentation therapy in α1-
antitrypsin deficiency. Eur Respir
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9 Stockley RA et al. Therapeutic
efficacy of alpha-1 antitrypsin
augmentation therapy on the
loss of lung tissue: an integrated
analysis of 2 randomised
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tomography densitometry. Respir
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10 Chapman KR et al.
Intravenous augmentation
treatment and lung density in
Optimal treatment of AATD-related COPD/
emphysema
Pharmacotherapy of emphysema in AATD
patients follows standard guidelines for COPD
and includes regular treatment with long-acting
bronchodilators active towards beta2 adrenergic
(salmeterol, formoterol, indacaterol, olodanterol,
vilanterol, etc) or muscarinic receptors (tiotropium,
glycopyrronium, umeclidinium) in monotherapy
or in combination as well as per-needed short-
acting bronchodilators (salbutamol, fenoterol). 2 In
some patients, inhaled corticosteroids, roflumilast,
mucolytics or long-term macrolides might be
recommended. Respiratory rehabilitation in all
patients and long-term oxygen therapy in those
with respiratory failure are an important part of
a non-pharmacologic approach. Prophylactic and
vigorous management of any respiratory infection
is particularly importance in view of AATD status.
Therefore, yearly vaccinations against influenza and
periodic vaccinations against pneumococcus are
recommended. Avoidance of exposure to tobacco
smoke or inhaled irritants is an important part of
treatment. Both active and passive smoking are
strongly contraindicated.
Lung transplantation is an option for patients
with severe AATD-related emphysema. There
are contradictory data regarding the survival
benefit in AATD patients; however, their quality
of life significantly improves. Likewise, surgical
lung volume reduction and endobronchial valve
placement seem to be beneficial in carefully
selected patients with AATD when treated in
centres experienced in both AATD and lung volume
reduction techniques (Box 3).
severe α1-antitrypsin deficiency
(RAPID): a randomised, double-
blind, placebo-controlled trial.
Lancet 2015;386;9991:360–8.
11 McElvaney NG et al. Long-
term efficacy and safety of α1
proteinase inhibitor treatment
for emphysema caused by
severe α1 antitrypsin deficiency:
an open-label extension trial
(RAPID-OLE). Lancet Respir Med
2017;5:51–60.
12 Chapman KR et al. Alpha 1
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in alpha 1 antitrypsin deficiency:
recent developments and clinical
implications. Int J Chron Obstruct
Pulmon Dis 2018;13:419–32.
13 Chorostowska-Wynimko
J. Disease modification in
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2016;13(6):807–15.
14 Horváth I et al Diagnosis and
management of α1-antitrypsin
deficiency in Europe: an expert
survey. ERJ Open Res 2019;5(1).
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15 Greulich T et al. Safety of
bi-weekly intravenous therapy
with alpha-1 antitrypsin. Eur
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10.1183/1393003.
16 Teschler H. Long-term
experience in the treatment of
α1-antitrypsin deficiency: 25
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Eur Respir Rev 2015;24:46–51.