Safety of bi-weekly intravenous therapy with alpha-1 antitrypsin

Greulich, Timm; Chlumský, J; Wencker, Marion; Vit, Oliver; Fries, Michael; Chung, Thomas; Vogelmeier, Claus; McElvaney, N.G.

doi:10.1183/1393003.congress-2017.pa710

Cited by 2 publications

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“…There is increasing interest in higher AAT doses: a recent pilot study found that normalising serum AAT levels in AATD patients by increasing dosing from 60 to 120 mg·kg −1 per week further reduced markers of residual proteolytic and inflammatory activity [34]. In addition, an analysis of patients who received 120 mg·kg −1 AAT or placebo to cover 2-week periods in the RAPID clinical trial programme found no increase in the infusion-adjusted event rate at 24 h and 72 h after administration [35]. The clinical utility and long-term safety of higher doses require further study and trials are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey

et al. 2019

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Despite recent improvements, α1-antitrypsin deficiency (AATD) remains a rarely diagnosed and treated condition. To assess the variability of AATD diagnosis/treatment in Europe, and to evaluate clinicians’ views on methods to optimise management, specialist AATD clinicians were invited to complete a web-based survey.Surveys were completed by 15 physicians from 14 centres in 13 European countries. All respondents perceived the AATD diagnosis rate to be low in their country; 77% of physicians believed that ∼15% of cases were diagnosed. Low awareness was perceived as the greatest barrier to diagnosis. Spirometry was considered more practical than quantitative computed tomography (QCT) for monitoring AATD patients in clinical practice; QCT was considered more useful in trials. AAT therapy provision was reported to be highly variable: France and Germany were reported to treat the highest proportion (∼60%) of diagnosed patients, in contrast to the UK and Hungary, where virtually no patients receive AAT therapy. Most clinicians supported self-administration and extended dosing intervals to improve convenience of AAT therapy.This survey indicates that AATD diagnosis and management are highly heterogeneous in Europe; European cooperation is essential to generate data to support access to AAT therapy. Improving convenience of AAT therapy is an ongoing objective.

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Section: Discussionmentioning

confidence: 99%

Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey

et al. 2019

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“…Two different measures comparing AE rates were calculated: exposure-adjusted event rates (EAER), defined as all TEAE occurring during the trial divided by the cumulative exposure of the respective group (60 or 120 mg/kg AAT or matching placebo), and infusion-adjusted event rates as TEAE occurring in the 7-day period up to and following a bi-weekly 120 mg/kg infusion or matching placebo (Table 1). 35 During RAPID-RCT, 75 patients in the AAT group received 333 infusions with 120 mg/kg AAT during 321 sequences and in the pooled dataset of RAPID-RCT and RAPID-OLE studies, 933 bi-weekly infusions during 884 sequences in 137 patients were identified. Results show that the EAER was 5.8844 for patients receiving 60 mg/kg versus 5.7038 for patients receiving 120 mg/kg (p=0.681); for serious TEAE, the EAER was 0.3741 for 60 mg/kg versus 0.4074 for 120 mg/kg (p=0.850).…”

Section: Doctor Tim Greulichmentioning

confidence: 99%

“…Pooled data from the RAPID randomised control trial and the open label extension trials-comparing differences in treatment emergent adverse events between weekly AAT (60 mg/kg) and bi-weekly AAT (120 mg/kg) 35. …”

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confidence: 99%

Focussing on The Patient: Future Prospects in Alpha 1 Management

Fricker¹

2018

EMJ Respir

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With new patient-centric and scientific networks being created, Prof Chorostowska-Wynimko explored how these initiatives, such as the European Alpha-1 Research Collaboration (EARCO) and the European Reference Network-LUNG Alpha1 Antitrypsin Deficiency (ERN-LUNG AATD Core Network), will help to advance the management of alpha 1-antitrypsin deficiency (AATD) patients. EARCO plans to create a registry to gather information from centres across Europe and ERN-LUNG AATD plans to ensure highly specialised healthcare for AATD patients, including reliable AATD diagnostics across European laboratories. Explaining in more detail the plans for the new EARCO registry, Dr Barrecheguren argued the case for another AATD registry to gather large-scale data that clinical trials cannot provide. She provided an overview of the new EARCO prospective follow-up registry, to be launched next year, which will integrate existing national AATD registries, enhance long-term follow-up and quality of data, and facilitate research and quality improvements across healthcare systems. Discussing one of the first initiatives of the ERN-LUNG AATD Core Network, Dr Ferrarotti explored how to align AATD testing across Europe with the creation of European LAB-NET, an initiative first involving six European centres that will co-operate to collect, develop, verify, and make reference materials available for molecular and biochemical tests to correctly diagnose AATD and provide quality control in the laboratory diagnosis. Dr Greulich reported on a post-hoc pooled analysis from the RAPID-randomised controlled trial (RAPID-RCT) and the RAPID-open label extension (RAPID-OLE) study, which compared the safety and tolerability of adverse event (AE) rates for two different alpha-1 antitrypsin (AAT) dosing patterns, weekly infusions of 60 mg/kg AAT, and bi-weekly infusions of 120 mg/kg AAT. Results showed there were no significant differences for exposure-adjusted event rates (p=0.850), infusion-adjusted event rates (p=0.344), and serious treatment emergent AE (TEAE) (p=1.0); TEAE occurring in the first 24 and 48 hours were comparable for both groups. Prof Sandhaus presented the results of a telephone survey from the USA AlphaNet organisation of self-infusion practices in 555 patients with AATD. The survey found that 7.9% of respondents self-administered AAT and 92.1% who did not. Of the 44 patients who self-administered AAT, 95.4% reported being very satisfied and 4.6% were satisfied with their treatment.

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Safety of bi-weekly intravenous therapy with alpha-1 antitrypsin

Cited by 2 publications

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Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey

Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey

Focussing on The Patient: Future Prospects in Alpha 1 Management

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Safety of bi-weekly intravenous therapy with alpha-1 antitrypsin

Cited by 2 publications

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Diagnosis and management of α1-antitrypsin deficiency in Europe: an expert survey

Diagnosis and management of α1-antitrypsin deficiency in Europe: an expert survey

Focussing on The Patient: Future Prospects in Alpha 1 Management

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Product

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Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey

Diagnosis and management of α₁-antitrypsin deficiency in Europe: an expert survey