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Table 1 Studies on augmentation therapy

From: Alpha-1 antitrypsin deficiency: outstanding questions and future directions

Authors

Dose

Type of study

End Point

Results

Non-randomised studies

 Seersholm et al., 1999 [58]

60 mg/kg/7 days

Observational, with control group

(n = 295)

FEV1 decline

Less FEV1 decline in treated group (56 vs 75 ml/y; p = 0,02)

Greater benefit for patients with FEV1:31–65%

 American AAT Deficiency Registry Study Group, 1998 [50]

33%, weekly

43% biweekly

24% monthly

Observational, with control group

(n = 1129)

FEV1 decline

Mortality

Reduction of mortality (OR 0,64; p = 0,02)

Less FEV1 decline in patients with FEV1 35–49%, treated

(66 vs 93 mL/y; p = 0,03)

 Wencker et al., 2001 [59]

60 mg/kg/7 days

Observational cohort. No control group (n = 96)

FEV1 decline

Less FEV1 decline during treatment (49,2 vs 34,2 mL/Y, p = 0,019). Lowest decline in FEV1 > 65% (256 vs 53 ml/Y, p = 0,001)

 Tonelli et al., 2009 [60]

 

Observational with control group (n = 164)

FEV1 decline

Mortality

Increase in FEV1: 10.6 ± 21.4 mL/Y; p = 0.05).

No differences on mortality

Randomised studies

 Dirksen et al., 1999 [64]

250 mg/kg/28 days

RCT (n = 66)

FEV1:30–80%

FEV1 decline, lung density

No significant effects on lung function

Trend towards a favourable effect reducing loss of lung tissue

 Dirksen et al., 2009 [68]

60 mg/kg/7 days

RCT (n = 77)

FEV1:25–80%

Lung function, QoL, exacerbations, lung density

Reduction in loss of lung density measured by CT in treated patients (p = 0.049)

No differences on FEV1 or DLCO

No differences on exacerbations frequency

 Chapman et al., 2015 [72]

60 mg/kg/7 days

RCT (n = 180)

Pi*ZZ, rare or null genotypes

AAT < 11 mM, Emphysema on CT, FEV1:35–70%

Lung function, QoL, exacerbations, lung density

Reduction in loss of lung density measured by CT in treated patients(p = 0,03). No differences on FEV1 or DLCO. No differences in QoL

Meta-analysis

 Chapman el al, 2009 [70]

 

Meta-analysis of studies on treated patients vs controls form Canadian Registry (n = 1509)

FEV1 decline

Reduction of 26% on FEV1 decline (17,9 ml/Y) in patients on treatment with ev AAT. Effect due to subjects with FEV1: 30–65%

 Gotzsche and Johansen, 2010 [71]

60 mg/kg/7 days

Meta-analysis Cochrane from 2 RCT (n = 140)

FEV1 Decline

DLCO

Lung density

Exacerbations

Lower lung density loss in treated patients (p = 0.03)

No differences in lung function

No differences in exacerbations

 Stockley et al., 2010 [69]

60 mg/kg/7 days

Integrated analysis of lung density studies

Lung density loss

FEV1 decline

Lower lung density loss in treated patients (1.73 vs 2.74 g/L, p = 0.006)

No differences in FEV1 decline

Marciniuk et al., 2012 [63]

 

Meta-analysis of all studies including treated patients with ev AAT vs controls

All parameters

Reduction in lung density loss measured by CT.

Reduction on mortality

Studies on exacerbations

 Lieberman, 2000 [73]

55% weekly

37% biweekly

8% monthly

Observational

(online survey)

n = 89

Exacerbations frequency

Reduction on exacerbations frequency from 3 to 5/year to 0–1/year on treatment with ev AAT

 Stockley et al., 2002 [74]

60mgs/kg/7 days

Descriptive

(n = 12)

Inflammatory biomarkers in sputum

Reduction of LTB4 after treatment

 Barros-Tizón et al., 2012 [75]

180 mg/kg/21 days

Retrospective (pre-post AAT treatment)

Frequency and severity of exacerbations

Reduction on number and severity of exacerbations and hospital admissions related costs

  1. Adapted from Casas F et al. Arch Bronconeumol 2015; 51:185–192 (ref. [38])