Title: Human alpha1-proteinase inhibitor for treating emphysema [ID856]
Funder: Department of Health and Social Care

Abstract: To evaluate the benefits and costs of human alpha 1-proteinase inhibitor within its marketing authorisation for treating emphysema for national commissioning by NHS England.

Lay abstract: Emphysema is a chronic lung disease in which the walls of the air sacs are damaged and break down causing them to enlarge. This makes the lungs baggy and less able to move the air in and out. The symptoms include coughing, wheezing, breathlessness, and frequent chest infections. Exacerbations often occur, where there is a rapid and sustained worsening of symptoms. Alpha 1-antitrypsin is a protein made in the liver that circulates in blood plasma. It protects the lungs from damage by enzymes such as neutrophil elastase. Some people have a genetic mutation that causes them to have low levels of alpha 1-antitrypsin. This deficiency can mean that neutrophil elastase damages cells in the lungs, causing emphysema. Severe alpha 1-antitrypsin deficiency is defined as serum alpha 1-antitrypsin concentration below 11 micromolar.(1) Alpha1-antitrypsin associated emphysema is often rapidly progressive and more severe than other forms of chronic obstructive pulmonary disease (COPD). People with alpha1-antitrypsin deficiency who smoke can have COPD symptoms in their 20s, whereas people with alpha1- antitrypsin deficiency who have never smoked are more likely to have symptoms over the age of 40. Severe alpha 1-antitrypsin deficiency can also cause disease in other organs such as the liver. Between 1 in 1600 and 1 in 5000 newborn babies have alpha 1-antitrypsin deficiency, but not all will develop emphysema.(2) Based on a disease registry in the West Midlands, it is estimated that 670 people in England have emphysema caused by alpha 1-antitrypsin deficiency.(1) About 540 of these people (80%) will have clinically significant emphysema that requires treatment.(2) Some people with COPD have undiagnosed alpha 1-antitrypsin deficiency.(3) Currently, the treatment for emphysema is the same regardless of whether people have alpha 1-antitrypsin deficiency or they do not. NICE clinical guideline 101 recommends that people with COPD should be provided with help to stop smoking and should be offered pneumococcal vaccination and an annual influenza vaccination. NICE clinical guideline 101 recommends initial treatment with short-acting bronchodilators. For people who remain breathless or have exacerbations despite using short-acting bronchodilators as required, NICE clinical guideline 101 recommends a sequence of inhaled treatments. These treatments may include a long-acting beta2 agonist (LABA), a long- acting muscarinic antagonist (LAMA) or inhaled corticosteroids, alone or in combination. Some people may have oral therapy with slow-release theophylline or a mucolytic. Additional treatment options include pulmonary rehabilitation (a multidisciplinary programme of supervised exercise training and education), oxygen therapy and, for those with severe disease, lung transplantation and lung volume reduction. With the exception of smoking cessation and the avoidance of other environmental risk factors, current treatments for emphysema caused by alpha 1-antitrypsin deficiency aim to alleviate symptoms and do not slow down the progression of the disease. Replacement therapy (also known as augmentation therapy) aims to boost the levels of alpha 1-antitrypsin in the blood. It involves an intravenous infusion of alpha 1-proteinase inhibitor derived from the blood plasma of healthy donors. NICE clinical guideline 101 does not recommend replacement therapy for people with alpha1-antitrypsin deficiency and COPD. NICE clinical guideline 101 notes that people with alpha 1-antitrypsin deficiency should be the opportunity to be referred to a specialist centre to discuss the clinical management of this condition. References 1. Miravitlles M, Herr C, Ferrarotti I et al. (2010) Laboratory testing of individuals with severe alpha1-antitrypsin deficiency in three European centres. European Respiratory Journal 35(5):960-8 2. NIHR Horizon Scanning Centre, 2014. Briefing note: Alpha-1 antitrypsin (Respreeza) for emphysema associated with alpha-1 antitrypsin deficiency – maintenance therapy. Accessed: February 2018 3. Alpha-1 UK Support Group, 2015. A health care professional’s guide to alpha-1 antitrypsin deficiency. Accessed: February 2018

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY