HPE Alpha 1 Antitrypsin Deficiency | Page 18

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 1 Janciauskiene S et al. The multifaceted effects of Alpha1- antitrypsin on neutrophil functions. Front Pharmacol 2018;9:341. 2 Miravitlles M et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1- antitrypsin deficiency. Eur Respir J 2017;50:1700610. 3 Gadek JE et al. Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease- antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest 1981;68(5):1158–65. 4 Wewers MD et al. Replacement therapy for alpha 1-antitrypsin defi ciency associated with emphysema. N Engl J Med 1987;316:1055–62. 5 The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med 1998;158(1):49–59. 6 Seersholm N et al. Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Eur Respir J 1997;10:2260–3. 7 Dirksen A et al. A randomised clinical trial of α1-antitrypsin 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 augmentation therapy. Am J Respir Crit Care Med 1999;160:1468–72. 8 Dirksen A et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1- antitrypsin deficiency. Eur Respir J 2009;33:1345–53. 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 clinical trials using computed tomography densitometry. Respir Res 2010;11:136. 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 antitrypsin to treat lung disease 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 emphysema related to Alpha-1 antitrypsin deficiency. COPD 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). pii:00171–2018. 15 Greulich T et al. Safety of bi-weekly intravenous therapy with alpha-1 antitrypsin. Eur Respir J 2017;50:PA710;DOI: 10.1183/1393003. 16 Teschler H. Long-term experience in the treatment of α1-antitrypsin deficiency: 25 years of augmentation therapy. Eur Respir Rev 2015;24:46–51.