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 |