Safety and Pharmacokinetics of 120 mg/kg versus 60 mg/kg Weekly Intravenous Infusions of Alpha-1 Proteinase Inhibitor in Alpha-1 Antitrypsin Deficiency: A Multicenter, Randomized, Double-Blind, Crossover Study (SPARK)

Campos, Michael; Kueppers, Friedrich; Stocks, James M.; Strange, Charlie; Chen, Junliang; Griffin, Rhonda; Wang-Smith, Laurene; Brantly, Mark

doi:10.3109/15412555.2013.800852

Cited by 58 publications

(47 citation statements)

References 21 publications

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“…dose that produces a mean trough serum level of 27.7 μM to 60 mg·kg −1 i.v. doses weekly that produce trough levels of 17.3 μM [98,99]. Because the AAT level in serum and in BAL of MZ individuals averages at 20 μM, a positive trial will prompt a re-evaluation of the evidence by which most MZ subjects remain untreated.…”

Section: Risk Of Asthma In the Mz Populationmentioning

confidence: 99%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2-5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case-control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.

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Section: Risk Of Asthma In the Mz Populationmentioning

confidence: 99%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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“…Five RCTs38–42 with 176 participants investigated differences between dosing regimens of a product38 or made comparisons between different products 39–42. Campos et al38 used a double-blind crossover study of 60 versus 120 mg/kg/week of Prolastin-C to investigate safety and pharmacokinetics in 30 patients.…”

Section: Resultsmentioning

confidence: 99%

Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review

Edgar¹,

Patel²,

Bayliss³

et al. 2017

COPD

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BackgroundAlpha-1 antitrypsin deficiency (AATD) is a rare genetic condition predisposing individuals to chronic obstructive pulmonary disease (COPD). The treatment is generally extrapolated from COPD unrelated to AATD; however, most COPD trials exclude AATD patients; thus, this study sought to systematically review AATD-specific literature to assist evidence-based patient management.MethodsStandard review methodology was used with meta-analysis and narrative synthesis (PROSPERO-CRD42015019354). Eligible studies were those of any treatment used in severe AATD. Randomized controlled trials (RCTs) were the primary focus; however, case series and uncontrolled studies were eligible. All studies had ≥10 participants receiving treatment or usual care, with baseline and follow-up data (>3 months). Risk of bias was assessed appropriately according to study methodology.ResultsIn all, 7,296 studies were retrieved from searches; 52 trials with 5,632 participants met the inclusion criteria, of which 26 studies involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments (largely transplantation). Studies were grouped into four management themes: COPD medical, COPD surgical, AATD specific, and other treatments. Computed tomography (CT) density, forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide, health status, and exacerbation rates were frequently used as outcomes. Meta-analyses were only possible for RCTs of intravenous augmentation, which slowed progression of emphysema measured by CT density change, 0.79 g/L/year versus placebo (P=0.002), and associated with a small increase in exacerbations 0.29/year (P=0.02). Mortality following lung transplant was comparable between AATD- and non-AATD-related COPD. Surgical reduction of lung volume demonstrated inferior outcomes compared with non-AATD-related emphysema.ConclusionIntravenous augmentation remains the only disease-specific therapy in AATD and there is evidence that this slows decline in emphysema determined by CT density. There is paucity of data around other treatments in AATD. Treatments for usual COPD may not be as efficacious in AATD, and further studies may be required for this disease group.

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“…In addition, it has been postulated that the level of ␣ 1 -AT obtained by replacement therapy could be somewhat related to the long-term clinical efficacy obtained. The recently launched SPARK trial, aimed at comparing two different doses of ␣ 1 -AT for replacement therapy, is evaluating this theory [18].…”

Section: English Versionmentioning

confidence: 99%

“…Par ailleurs, il a été suggéré que le taux d'␣ 1 -AT plasmatique obtenu sous traitement substitutif puisse influencer en partie l'efficacité clinique du traitement à long-terme. L'étude SPARK, débutée récemment, a pour but de comparer deux posologies différentes d'␣ 1 -AT au cours du traitement substitutif et permettra d'évaluer cette hypothèse [18].…”

Section: Version Françaiseunclassified