Alpha 1 Antitrypsin Therapy in Patients with Alpha 1 Antitrypsin Deficiency: Perspectives from a Registry Study and Practical Considerations for Self-Administration During the COVID-19 Pandemic

Figures & data

Table 1 Case Study of a Patient Diagnosed with Bronchiectasis and AATD with Frequent Exacerbations, Who Has Been Self-Administering AAT Therapy for Over 3 Years

Patient details
Gender	Female
Age, years	52
Height, cm	164
Weight, kg	56
Clinical presentation
Lung infection frequency	Recurrent infections and pneumonia
	3–4 per year
	No other illnesses
Physical examination	Left lung is weak and has always been weak
	Coarse crackle, left more than right
	Sputum microbiology: sometimes pneumococci, sometimes haemophilus
Serum AAT, g/L	0.3
AAT genotype	PI*ZZ
Details of treatment
Year that self-administration of AAT started	2017
Medication	Human alpha 1 proteinase inhibitor (Respreeza [CSL Behring, GmbH, Emil-von-Behring-Straße, Marburg, Germany])
Dose	4–5 g per vial (60 mg/kg)
Schedule	Weekly
Patient training and feedback	Patient received training prior to beginning self-administration
Patient-reported benefits	● Reduction in exacerbation frequency with AAT therapy from 2017 to 2019
	● Improved QoL and independence compared with HCP-administered therapy
	● Online support for self-administration
	● Improved awareness of AATD and the associated benefits of self-administration among family members compared with HCP-administered therapy
	● Reduction in time spent receiving treatment and travelling to treatment centers compared with hospital-administered AAT therapy
	● Logistical flexibility – self-administration can be carried out as and where required by the patient
Patient-reported challenges	None

Abbreviations: AAT, Alpha 1 Antitrypsin; AATD, Alpha 1 Antitrypsin deficiency; HCP, healthcare professional; QoL, quality of life.

Figure 1 Factors considered when selecting appropriate patients with AATD to begin on self-administration therapy.

Abbreviation: FEV₁, forced expiratory volume in 1 second.

Table 2 Five Competencies Patients are Required to Demonstrate Before Beginning Therapy

	Competency Skill
1	Hygiene and infection control
2	Drug reconstitution and administration
3	IV access management and maintenance
4	Safe storage of IV therapy kit
5	Correct disposal of sharps

Note: Data from West Suffolk NHS Foundation Trust Policy.⁴⁴

Abbreviation: IV, intravenous.

Table 3 The Teaching of Self-Administration IV AAT Therapy to Patients and/or a Spouse or Relative, Should Focus on a Variety of Aspects Covering Pre-, During and Post-Administrative Care

Self-Administration Training Should Focus on:
General knowledge of AATD
Identification of common AEs
Preparation, storage and administration of AAT therapy
First aid measures
Dosage calculation
Aseptic techniques
Performing canalization
Correct storage and disposal of needles/sharps
Record keeping of treatment

Abbreviations: AE, adverse event; AAT, Alpha 1 Antitrypsin; AATD, Alpha 1 Antitrypsin deficiency; IV, intravenous.

Figure 2 Practical aspects taught to patients for self-administering AAT therapy.

Abbreviation: AAT, Alpha 1 Antitrypsin.

Table 4 Information Required by Patients and Clinicians When Submitting an Online AE Report to a Local Authority

AE Reported by a Patient

AE Reported by a Clinician

● Age and sex of patient ● Description of the side effects ● Name of medicine (brand name and active ingredient) ● Medicine batch number ● Whether the patient was taking any other medicines at the time ● Any other health conditions

● Age and sex of patient ● Whether the infection was diagnosed through testing or based on clinical symptoms alone ● Description of the side effects ● Name of medicine (brand name and active ingredient) ● Dose and duration of treatment with relevant medicine ● Medicine batch number ● Any other medicines taken at the time of AE, including non-prescription medicines or contraceptives ● Any other health conditions

Note: Data from European Medicines Agency.⁵⁷

Abbreviation: AE, adverse event.

Table 5 Studies of AAT Therapy in Patients with COVID-19*

Study	Study Identifier	Phase	Interventions	Key Findings	Estimated Study Completion Date
A) Completed studies
Individual Treatment of COVID-19 by Application of Alpha-1-antitrypsin^Citation74	CORSAAR-AAT (NCT04799873; ClinicalTrials.gov)	Observational (N = 9)	● Inhaled AAT therapy ● Combined inhaled/ IV AAT therapy ● Remdesivir ● Dexamethasone	Compared with baseline, treatment with AAT therapy resulted in: ● An overall improvement in respiratory status (per WHO severity class) in all patients ● A reduction in serum CRP concentrations, with fluctuations in individual patients ● A decrease in viral load in all patients	December 2020
B) Ongoing studies
Trial of Alpha One Antitrypsin Inhalation in Treating Patient With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)	NCT04385836 (ClinicalTrials.gov)^Citation75	Phase 1 (N = 150)	● Inhaled AAT therapy via nebulizer ● Placebo via nebulizer	September 2020
A randomized double-blind placebo-controlled, pilot trial of intravenous plasma-purified alpha-1 antitrypsin for severe COVID-19 illness	2020-001391-15 (EudraCT)^Citation76	Phase 2 (N = 36)	● IV AAT therapy ● Placebo	April 2021
A Multicenter, Randomized, Open-label, Parallel Group Pilot Study to Evaluate the Safety and Efficacy of Prolastin Plus Standard Medical Treatment (SMT) Versus SMT Alone in Hospitalized Subjects With COVID-19	NCT04495101 (ClinicalTrials.gov)^Citation77	Phase 2 (N = 100)	● IV AAT therapy + SMT ● SMT	June 2021
Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)	NCT04547140 (ClinicalTrials.gov)^Citation78	Phase 2 (N = 100)	● IV AAT therapy + SMT ● Placebo + SMT	February 2022

Note: *Information correct as of August 2021.

Abbreviations: AAT, Alpha 1 Antitrypsin; CRP, C-reactive protein; IV, intravenous; SMT, standard medical treatment; WHO, World Health Organization.

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