Studies on augmentation therapy for α1-antitrypsin deficiency

Study designAuthor, year [Ref.]InterventionComparatorPrimary outcomeSubjects nDuration of treatmentEffect of treatment
RCT vs placeboDirksen, 1999 [51]250 mg·kg−1 augmentation 4 weekly625 mg·kg−1 albumin solutionFEV1 decline58≥3 yearsFEV1 decline ns difference 59 vs 79 mL·year−1 (p=0.25); reduced CT decline 2.6 vs 1.5 g·L−1·year−1 (p=0.07)
Dirksen, 2009 [52]60 mg·kg−1 Prolastin weekly2% albumin solutionCT densitometry77≥2 yearsReduced CT decline 1.4 vs 2.2 g·L−1·year−1 (p=0.06)
Chapman, 2015 [53]60 mg·kg−1 Zemaira weeklyLyophilised preparationCT densitometry180≥2 yearsReduced CT decline 1.5 vs 2.2 g·L−1·year−1 (p=0.03)
RCT vs active comparatorStoller, 2002# [88]60 mg·kg−1 Prolastin weekly60 mg·kg−1 Respitin weeklySerum AAT level28≥12 weeksEquivalence for primary outcome, ns difference FEV1, DLCO, urinary desmosine
Stocks, 2006# [89]60 mg·kg−1 Prolastin weekly60 mg·kg−1 Zemaira weeklySerum AAT level44≥10 weeksEquivalence for primary outcome
Stocks, 2010# [90]60 mg·kg−1 Prolastin-C weekly60 mg·kg−1 Prolastin weeklyPlasma AAT level2410 weeksEquivalence for primary outcome
Campos, 2013# [91]120 mg·kg−1 Prolastin-C weekly60 mg·kg−1 Prolastin weeklyPlasma AAT level, safety308 weeksEquivalence for primary outcome, ns difference in adverse events
Sandhaus, 2014# [92]60 mg·kg−1 Glassia weekly60 mg·kg−1 Prolastin weeklyPlasma AAT level50≥1 weeksEquivalence for primary outcome, ns difference FEV1 or FVC
Observational with controlSeersholm, 1997 [93]60 mg·kg−1 Prolastin or Trypsone weeklyNo augmentationFEV1 decline2951 yearReduced FEV1 decline 53 vs 75 mL·year−1 (p=0.02)
AAT registry group, 1998 [8]60 mg·kg−1 Prolastin weekly↓ frequency or no augmentationFEV1 decline, survival112912–86 monthsBetter survival (p=0.001), ns difference in FEV1 decline overall (p=0.40), if FEV1 35–49%, decline lower on treatment (73 vs 93 mL·year−1, p=0.01)
Wencker, 2001 [95]60 mg·kg−1 augmentation weeklyData prior to augmentationFEV1 decline96≥12 monthsReduced FEV1 decline 34 vs 49 mL·year−1 (p=0.02)
Stoller, 2003 [94]Any dosing regimen augmentationUsual careAdverse events112912–86 months83% augmented patients had no adverse events; rate 0.02 events per patient per month
Tonelli, 2009 [96]Any dosing regimen augmentationNo augmentationFEV1 decline164Mean 42 monthsReduced FEV1 decline 37 vs 46 mL·year−1 (p=0.05)
Barros-Tizon, 2012 [97]60 mg·kg−1 Prolastin or Trypsone at any intervalData prior to augmentationExacerbation rate12718 monthsReduced exacerbation rate 1.2 vs 1 per year (p<0.01), reduced hospitalisation costs
Observational, no controlWewers, 1987 [82]60 mg·kg−1 augmentation weeklyN/ASerum AAT level, safety216 monthsAAT level improved vs baseline, low adverse event rate (i.e. safe)
Schmidt, 1988 [98]60 mg·kg−1 augmentation weeklyN/ASerum AAT level206 monthsAAT level maintained at 35% of normal (equivalent to PiMZ)
Barker, 1994 [99]60 mg·kg−1 Prolastin weeklyN/AFunctional status1412–48 months12 out of 14 patients stabilised self-reported functional status
Miravitlles, 1994 [101]60 mg·kg−1 Prolastin weekly+N/ASafety, AAT level13Up to 6 yearsNo significant adverse events; 10 out of 13 trough AAT >50 mg·dL−1
Barker, 1997 [100]120 mg·kg−1 Prolastin fortnightlyN/AAAT level, safety2320 weeksTrough levels inadequate with fortnightly dosing, treatment safe
Schwaiblmair, 1997 [102]60 mg·kg−1 Prolastin weeklyN/AFEV1203 yearsFEV1 decline 36 mL·year−1
Wencker, 1998 [103]60 mg·kg−1 Prolastin weeklyN/AFEV1 decline, safety4433.1–82.8 monthsFEV1 decline 57 mL·year−1 on treatment, which was deemed safe
Campos, 2009 [106]Any form of augmentationN/ACompared age >60 years to <60 years10621 yearOlder subjects exhibited more indolent disease with fewer exacerbations
Campos, 2009 [105]Any form of augmentationN/AExacerbations9221 yearMean exacerbations 2.4 per year, 17 days per episode
Vidal, 2010 [108]60 mg·kg−1 Trypsone weeklyN/ASafety2324 weeks1 out of 555 infusions had a treatment related adverse event
Subramanian, 2012 [107]60 mg·kg−1 Prolastin weeklyN/APET CT1012 weeksns difference in PET signal on treatment

RCT: randomised controlled trial; FEV1: forced expiratory volume in 1 s; ns: nonsignificant; CT: computed tomography; DLCO: diffusing capacity of the lung for carbon monoxide; AAT: α1-antitrypsin; FVC: forced vital capacity; N/A: not applicable; PET: positron emission tomography. #: crossover study (either wholly or as follow on for the placebo group); : some patients changed to 120–180 mg·kg−1, 2–3 weekly +: changed to 240 mg·kg−1, 4 weekly.