Tolerability and safety of aN alpha-1-antitrypsin concentrate in augmentation therapy in patients with pulmonary emphysema secondary to deficiency of alpha-1-antitrypsin

 

Torres Ma, Gáldiz JBb, Gispert Pc, Casas Fd, Bustamante Ae, Blanco If, Rodríguez JLg, Barros-Tizón JCa, *Vidal Rc, *Miravitlles Mh.

 

*Coordinating Investigators. aPneumology Department, Complexo Hospitalario Universitario de Vigo, Vigo. bPneumology Department, Hospital de Cruces, Cruces-Barakaldo. cPneumology Department, Hospital Vall d´Hebron, Barcelona. dPneumology Department, Hospital Universitario San Cecilio, Granada. ePneumology Department, Hospital de Sierrallana, Torrelavega. fRespiratory Unit, Hospital Valle del Nalón, Langreo. gPneumology Department, Hospital Clínico San Carlos, Madrid. hPneumology Department; Hospital Clínic i Provincial, Barcelona. All Centres in Spain.

 

Background:
augmentation therapy with alpha-1-antitrypsin (AAT) has demonstrated biochemical efficacy in restoring serum AAT levels above protective threshold.

 

Objective:
to evaluate tolerability and safety of a solvent detergent-treated, nanofiltrated (15 nm), human plasma-derived AAT (Trypsone®; Instituto Grifols; Barcelona) launched in 2003.

 

Design:
prospective, observational study of a cohort of subjects eligible for augmentation therapy. Parameters used to evaluate tolerability are changes in vital signs and adverse events (AE) during intravenous infusions of the product. Monitoring of AE and laboratory parameters (LP) during the follow-up are used to assess safety.

 

Results:
data from the first 13-month follow-up are shown.

 

Table 1: Main baseline features of the subjects (18 enrolled; 17 received the study drug).

 

Baseline Feature	Mean (95 % CI)	Median (Min-Max)		Baseline Feature	N (%)
Age (years)	51.89 (46.61-57.17)	49.00 (39-74)		Female Male	9 (50.00) 9 (50.00)
Serum AAT (mg/dl)	38.53 (31.41-45.66)	37.00 (19.00-64.00)		Index case Non-index case	15 (83.33)  3 (16.67)
FEV1 (% predicted)	47.33 (39.81-54.85)	45.65 (21.70-79.00)		PIZZ PISZ	17 (94.44) 1 (5.56)
Years since diagnosis	5.07 (3.34-6.80)	4.51 (0.55-11.00)		Ex-smoker Never smoker	15 (83.33)  3 (16.64)
				Never Tx Previous Tx	7 (38.89) 11 (61.11)
Confidence interval (CI); minimum (Min); maximum (Max); absolute (N) and relative (%) frequency; forced expiratory volume in 1 second (FEV1); AAT augmentation therapy (Tx).

 

Overall 1,450 g of the drug (28 batches) were administered (161 infusions). Two dosing patterns were identified: 60 mg/kg/week (5 subjects); 180 mg/kg/3 weeks (12 subjects). The mean total dose was 9,019 mg; 16,500 mg the maximum. Exposure-days were 10 (median); 17 maximum. The mean infusion rate was 0.054 ml/kg/minute; 0.071 ml/kg/minute the maximum. No clinically relevant changes in vital signs were observed. Neither AE potentially related to the study drug nor clinically relevant changes in LP occurred.

 

Conclusions:
data obtained support that therapy with the study drug is safe and well tolerated, in line with previous experience from clinical trials.

 

 

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