Is Prolastin (Alpha-1 Antitrypsin) home infusion medically indicated for a patient with Chronic Obstructive Pulmonary Disease (COPD) and Alpha-1 Antitrypsin Deficiency?

Prolastin Home Infusions Are Medically Indicated for This Patient

Based on the most recent 2025 Canadian Thoracic Society guidelines, this 50-year-old female with Alpha-1 Antitrypsin Deficiency and COPD meets the criteria for augmentation therapy, though critical missing information requires documentation before final approval. 1

Criteria Assessment

Patient Meets the Following Requirements:

• Age 18-65 years: Patient is 50 years old 1
• Documented Alpha-1 Antitrypsin Deficiency: Diagnosis of E88.01 confirmed 1
• Severe A1AT deficiency: Serum level <11 micromoles/L documented 1
• COPD with pulmonary impairment: FEV1 of 37% (<80% predicted) 1
• Documented emphysema: Required per guidelines 1
• Former smoker status: Patient is noted as former smoker 1

Critical Missing Information That Must Be Documented:

The 2025 Canadian Thoracic Society guidelines explicitly require that patients be "never or previously smoked" - meaning current smoking is an absolute contraindication. 1 However, the following gaps exist:

• Duration of smoking cessation: Guidelines require documentation that patient is no longer smoking, though specific duration requirements vary 1
• Confirmation of SERPINA1 genotype: Must document specific genotype (ZZ, SZ, or other deficiency-associated variants) 1
• Confirmation of optimal COPD therapy: Must document patient is receiving appropriate pharmacological and non-pharmacological COPD treatments 1

Evidence-Based Recommendation

The 2025 Canadian Thoracic Society meta-analysis and clinical practice guideline (the highest quality and most recent evidence) conditionally recommends A1AT augmentation therapy for patients meeting ALL of the following criteria: 1

1. Never or previously smoked (not currently smoking)
2. FEV1 <80% predicted
3. Documented emphysema
4. Documented SERPINA1 genotypes associated with A1AT deficiency
5. Severely reduced functional A1AT level (<11 mmol/L or <0.57 g/L)
6. Receiving optimal pharmacological and non-pharmacological therapies for COPD

This patient appears to meet criteria 2,3,5, and possibly 1, but requires documentation of criteria 4 and 6. 1

Clinical Benefits Supported by Evidence

The 2025 guidelines found high-quality evidence that augmentation therapy preserves CT scan lung density and very low-quality evidence suggesting mortality reduction. 1 The FDA-approved indication for Prolastin (and similar products like GLASSIA) is for "chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of Alpha1-PI." 2

Historical data from the 2003 ATS/ERS guidelines showed that patients with FEV1 31-65% predicted (which includes this patient at 37%) demonstrated the most significant benefit from augmentation therapy, with slowed FEV1 decline. 1 The NHLBI Registry data showed mortality benefit in treated patients (OR 0.79, p<0.02). 1

Dosing and Administration

Standard dosing is 60 mg/kg body weight once weekly by intravenous infusion. 2 The FDA label for GLASSIA (similar to Prolastin) specifies this can be administered by healthcare professionals or self-administered after appropriate training, making home infusions appropriate. 2

Critical Caveats and Required Actions Before Approval

Must Document Before Final Approval:

1. Smoking cessation confirmation: Verify patient has completely stopped smoking; some programs require 6 months cessation 3
2. SERPINA1 genotype: Obtain genetic testing with DNA sequencing to confirm deficiency-associated genotype (ZZ, SZ, or other pathogenic variants) 1
3. Optimal COPD management: Document patient is on appropriate bronchodilators, vaccinations, and other standard COPD therapies 1
4. Documented emphysema: Confirm emphysema presence via CT imaging 1

Additional Considerations:

• IgA deficiency screening: While not mentioned in the 2025 guidelines as an absolute requirement, the case notes this is missing. Patients with selective IgA deficiency and anti-IgA antibodies have increased risk of severe allergic reactions to blood products 2
• Phenotype confirmation: If patient has MS phenotype (not ZZ, SZ, or null variants), they would NOT qualify for therapy as MS phenotype maintains A1AT levels above the protective threshold 3

Common Pitfalls to Avoid

Do not approve augmentation therapy if: 1, 3

• Patient is currently smoking (absolute contraindication)
• A1AT level is ≥11 micromoles/L (not severe deficiency)
• Patient has MS phenotype only (insufficient deficiency)
• FEV1 is >80% predicted (insufficient impairment)
• Emphysema is not documented
• Patient is not on optimal COPD therapy first

The most common error is initiating augmentation therapy without confirming the specific SERPINA1 genotype, as not all low A1AT levels warrant treatment. 1, 3

Final Determination

Prolastin home infusions are CONDITIONALLY INDICATED pending documentation of: (1) confirmed smoking cessation, (2) SERPINA1 genotype showing severe deficiency variant, and (3) optimal COPD therapy. 1 Once these elements are confirmed, weekly Prolastin infusions at 60 mg/kg are medically appropriate and align with current evidence-based guidelines for preserving lung density and potentially reducing mortality in this patient with severe A1AT deficiency and moderate-to-severe COPD. 1, 2