Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)

Noel G McElvaney; Jonathan Burdon; Mark Holmes; Allan Glanville; Peter A B Wark; Philip J Thompson; Paul Hernandez; Jan Chlumsky; Helmut Teschler; Joachim H Ficker; Niels Seersholm; Alan Altraja; Riitta Mäkitaro; Joanna Chorostowska-Wynimko; Marek Sanak; Paul I Stoicescu; Eeva Piitulainen; Oliver Vit; Marion Wencker; Michael A Tortorici; Michael Fries; Jonathan M Edelman; Kenneth R Chapman; RAPID Extension Trial Group

doi:10.1016/S2213-2600(16)30430-1

Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)

Noel G McElvaney, Jonathan Burdon, Mark Holmes, Allan Glanville, Peter A B Wark, Philip J Thompson, Paul Hernandez, Jan Chlumsky, Helmut Teschler, Joachim H Ficker, Niels Seersholm, Alan Altraja, Riitta Mäkitaro, Joanna Chorostowska-Wynimko, Marek Sanak, Paul I Stoicescu, Eeva Piitulainen, Oliver Vit, Marion Wencker, Michael A TortoriciMichael Fries, Jonathan M Edelman, Kenneth R Chapman, RAPID Extension Trial Group

152 Citationer (Scopus)

Abstract

BACKGROUND: Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT.

METHODS: Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007.

FINDINGS: Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48.

INTERPRETATION: RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment.

FUNDING: CSL Behring.

Originalsprog	Engelsk
Tidsskrift	The Lancet Respiratory Medicine
Vol/bind	5
Udgave nummer	1
Sider (fra-til)	51-60
Antal sider	10
ISSN	2213-2600
DOI	https://doi.org/10.1016/S2213-2600(16)30430-1
Status	Udgivet - jan. 2017

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10.1016/S2213-2600(16)30430-1

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McElvaney, N. G., Burdon, J., Holmes, M., Glanville, A., Wark, P. A. B., Thompson, P. J., Hernandez, P., Chlumsky, J., Teschler, H., Ficker, J. H., Seersholm, N., Altraja, A., Mäkitaro, R., Chorostowska-Wynimko, J., Sanak, M., Stoicescu, P. I., Piitulainen, E., Vit, O., Wencker, M., ... RAPID Extension Trial Group (2017). Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). The Lancet Respiratory Medicine, 5(1), 51-60. https://doi.org/10.1016/S2213-2600(16)30430-1

Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). / McElvaney, Noel G; Burdon, Jonathan; Holmes, Mark et al.
I: The Lancet Respiratory Medicine, Bind 5, Nr. 1, 01.2017, s. 51-60.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

McElvaney, NG, Burdon, J, Holmes, M, Glanville, A, Wark, PAB, Thompson, PJ, Hernandez, P, Chlumsky, J, Teschler, H, Ficker, JH, Seersholm, N, Altraja, A, Mäkitaro, R, Chorostowska-Wynimko, J, Sanak, M, Stoicescu, PI, Piitulainen, E, Vit, O, Wencker, M, Tortorici, MA, Fries, M, Edelman, JM, Chapman, KR & RAPID Extension Trial Group 2017, 'Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)', The Lancet Respiratory Medicine, bind 5, nr. 1, s. 51-60. https://doi.org/10.1016/S2213-2600(16)30430-1

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title = "Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)",

abstract = "BACKGROUND: Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT.METHODS: Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007.FINDINGS: Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48.INTERPRETATION: RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment.FUNDING: CSL Behring.",

keywords = "Adolescent, Adult, Disease Progression, Female, Humans, Lung, Male, Pulmonary Emphysema, Regression Analysis, Respiratory Function Tests, Serine Proteinase Inhibitors, Total Lung Capacity, Treatment Outcome, Young Adult, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency, Journal Article, Randomized Controlled Trial",

author = "McElvaney, {Noel G} and Jonathan Burdon and Mark Holmes and Allan Glanville and Wark, {Peter A B} and Thompson, {Philip J} and Paul Hernandez and Jan Chlumsky and Helmut Teschler and Ficker, {Joachim H} and Niels Seersholm and Alan Altraja and Riitta M{\"a}kitaro and Joanna Chorostowska-Wynimko and Marek Sanak and Stoicescu, {Paul I} and Eeva Piitulainen and Oliver Vit and Marion Wencker and Tortorici, {Michael A} and Michael Fries and Edelman, {Jonathan M} and Chapman, {Kenneth R} and {RAPID Extension Trial Group}",

year = "2017",

month = jan,

doi = "10.1016/S2213-2600(16)30430-1",

language = "English",

volume = "5",

pages = "51--60",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency

T2 - an open-label extension trial (RAPID-OLE)

AU - McElvaney, Noel G

AU - Burdon, Jonathan

AU - Holmes, Mark

AU - Glanville, Allan

AU - Wark, Peter A B

AU - Thompson, Philip J

AU - Hernandez, Paul

AU - Chlumsky, Jan

AU - Teschler, Helmut

AU - Ficker, Joachim H

AU - Seersholm, Niels

AU - Altraja, Alan

AU - Mäkitaro, Riitta

AU - Chorostowska-Wynimko, Joanna

AU - Sanak, Marek

AU - Stoicescu, Paul I

AU - Piitulainen, Eeva

AU - Vit, Oliver

AU - Wencker, Marion

AU - Tortorici, Michael A

AU - Fries, Michael

AU - Edelman, Jonathan M

AU - Chapman, Kenneth R

AU - RAPID Extension Trial Group

PY - 2017/1

Y1 - 2017/1

N2 - BACKGROUND: Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT.METHODS: Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007.FINDINGS: Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48.INTERPRETATION: RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment.FUNDING: CSL Behring.

AB - BACKGROUND: Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT.METHODS: Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007.FINDINGS: Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48.INTERPRETATION: RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment.FUNDING: CSL Behring.

KW - Adolescent

KW - Adult

KW - Disease Progression

KW - Female

KW - Humans

KW - Lung

KW - Male

KW - Pulmonary Emphysema

KW - Regression Analysis

KW - Respiratory Function Tests

KW - Serine Proteinase Inhibitors

KW - Total Lung Capacity

KW - Treatment Outcome

KW - Young Adult

KW - alpha 1-Antitrypsin

KW - alpha 1-Antitrypsin Deficiency

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1016/S2213-2600(16)30430-1

DO - 10.1016/S2213-2600(16)30430-1

M3 - Journal article

C2 - 27916480

SN - 2213-2600

VL - 5

SP - 51

EP - 60

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 1

ER -

Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)

Abstract

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