Alpha-1 overview

What is alpha1-antitrypsin deficiency (alpha-1)?

Alpha1-antitrypsin deficiency (alpha-1) is an inherited disease that is characterized by a severe deficiency of alpha-1 antitrypsin (AAT) in the lungs. Low levels of circulating AAT allow potentially harmful enzymes, like neutrophil elastase, to remain in the lungs unchecked. Low levels of AAT, and the consequent proliferation of neutrophil elastase, leave lung tissue vulnerable to destruction, resulting in a decline in lung function. Alpha-1 may be a contributing cause of up to 3% of all COPD cases in the United States.1-3

Low levels of AAT can lead to serious lung destruction

AAT is a protein with potent protease inhibitor activity. Its main function is to protect normal lung tissue from proteolytic attack during inflammation, such as that caused by infection and inhaled irritants such as tobacco smoke. When low levels of AAT occur, the lungs are at risk for serious lung disease.2-5

What are the effects of AAT deficiency? Watch now:

Endogenous AAT is critical to safeguarding the lungs2

Lungs with normal AAT levels keep neutrophil elastase in check so that lung structure is preserved2

  • Neutrophil elastase is released in response to lung infection, injury, or inflammation5
  • Produced in the liver, AAT inhibits excess amounts of proteases2
  • Only laboratory testing can determine if an individual's AAT levels are sufficient6

Low levels of AAT leave lung tissue vulnerable to destruction2

In AAT-deficient individuals, excess neutrophil elastase cannot be neutralized, lung elastin is destroyed, and lung function is compromised2

  • Smoking, secondary smoke, dust, and exposure to fumes accelerate lung disease in patients with alpha-12,7
  • Bacterial infections are additional risk factors for lung disease in patients with alpha-12

PROLASTIN®-C (alpha1-proteinase inhibitor [human]) is indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of alpha1-PI (alpha1-antitrypsin deficiency).

The effect of augmentation therapy with any alpha1-proteinase inhibitor (alpha1-PI), including PROLASTIN-C, on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been conclusively demonstrated in randomized, controlled clinical trials. Clinical data demonstrating the long-term effects of chronic augmentation or maintenance therapy with PROLASTIN-C are not available.

PROLASTIN-C is not indicated as therapy for lung disease in patients in whom severe alpha1-PI deficiency has not been established.

PROLASTIN-C is contraindicated in IgA-deficient patients with antibodies against IgA due to the risk of severe hypersensitivity and in patients with a history of anaphylaxis or other severe systemic reactions to alpha1-PI.

Hypersensitivity reactions, including anaphylaxis, may occur. Monitor vital signs and observe the patient carefully throughout the infusion. Should hypersensitivity symptoms be observed, promptly stop infusion and begin appropriate therapy. Have epinephrine and other appropriate therapy available for the treatment of any acute anaphylactic or anaphylactoid reaction.

PROLASTIN-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions.

The most common drug-related adverse reaction observed at a rate of >5% in subjects receiving PROLASTIN-C was upper respiratory tract infection. The most serious adverse reaction observed during clinical trials with PROLASTIN-C was an abdominal and extremity rash in 1 subject.

Because PROLASTIN-C is made from human plasma, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.

Please click here for full Prescribing Information for PROLASTIN-C.


References

  1. World Health Organization. α1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ. 1997;75(5):397-415.
  2. Köhnlein T, Welte T. Alpha-1 Antitrypsin Deficiency—Clinical Aspects and Management. Bremen, Germany: UNI-MED Verlag AG; 2007.
  3. Brantly ML, Paul LD, Miller BH, Falk RT, Wu M, Crystal RG. Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms. Am Rev Respir Dis. 1988;138(2):327-336.
  4. Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with α1-antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179-1186.
  5. de Serres FJ. Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed. Environ Health Perspect. 2003;111(16):1851-1854.
  6. Data on file, Alpha-1 Genetics Laboratory at GeneAidyx LLC.
  7. Global Initiative for Chronic Obstructive Lung Disease. Pocket Guide to COPD Diagnosis, Management, and Prevention. 2015:1-28.