Elisabeth Bendstrup

Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis. / Trapnell, B. C.; Inoue, Y.; Bonella, F.; Morgan, C.; Jouneau, S.; Bendstrup, E.; Campo, I.; Papiris, S. A.; Yamaguchi, E.; Cetinkaya, E.; Ilkovich, M. M.; Kramer, M. R.; Veltkamp, M.; Kreuter, M.; Baba, T.; Ganslandt, C.; Tarnow, I.; Waterer, G.; Jouhikainen, T.; IMPALA Trial Investigators.

In: New England Journal of Medicine, Vol. 383, No. 17, 10.2020, p. 1635-1644.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Trapnell, BC, Inoue, Y, Bonella, F, Morgan, C, Jouneau, S, Bendstrup, E, Campo, I, Papiris, SA, Yamaguchi, E, Cetinkaya, E, Ilkovich, MM, Kramer, MR, Veltkamp, M, Kreuter, M, Baba, T, Ganslandt, C, Tarnow, I, Waterer, G, Jouhikainen, T & IMPALA Trial Investigators 2020, 'Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis', New England Journal of Medicine, vol. 383, no. 17, pp. 1635-1644. https://doi.org/10.1056/NEJMoa1913590

APA

Trapnell, B. C., Inoue, Y., Bonella, F., Morgan, C., Jouneau, S., Bendstrup, E., Campo, I., Papiris, S. A., Yamaguchi, E., Cetinkaya, E., Ilkovich, M. M., Kramer, M. R., Veltkamp, M., Kreuter, M., Baba, T., Ganslandt, C., Tarnow, I., Waterer, G., Jouhikainen, T., & IMPALA Trial Investigators (2020). Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis. New England Journal of Medicine, 383(17), 1635-1644. https://doi.org/10.1056/NEJMoa1913590

CBE

Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E, Campo I, Papiris SA, Yamaguchi E, Cetinkaya E, Ilkovich MM, Kramer MR, Veltkamp M, Kreuter M, Baba T, Ganslandt C, Tarnow I, Waterer G, Jouhikainen T, IMPALA Trial Investigators. 2020. Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis. New England Journal of Medicine. 383(17):1635-1644. https://doi.org/10.1056/NEJMoa1913590

MLA

Trapnell, B. C. et al. "Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis". New England Journal of Medicine. 2020, 383(17). 1635-1644. https://doi.org/10.1056/NEJMoa1913590

Vancouver

Trapnell BC, Inoue Y, Bonella F, Morgan C, Jouneau S, Bendstrup E et al. Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis. New England Journal of Medicine. 2020 Oct;383(17):1635-1644. https://doi.org/10.1056/NEJMoa1913590

Author

Trapnell, B. C. ; Inoue, Y. ; Bonella, F. ; Morgan, C. ; Jouneau, S. ; Bendstrup, E. ; Campo, I. ; Papiris, S. A. ; Yamaguchi, E. ; Cetinkaya, E. ; Ilkovich, M. M. ; Kramer, M. R. ; Veltkamp, M. ; Kreuter, M. ; Baba, T. ; Ganslandt, C. ; Tarnow, I. ; Waterer, G. ; Jouhikainen, T. ; IMPALA Trial Investigators. / Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis. In: New England Journal of Medicine. 2020 ; Vol. 383, No. 17. pp. 1635-1644.

Bibtex

@article{13038264a2514a17871ff76710bb22ec,
title = "Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis",
abstract = "BACKGROUND Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).",
author = "Trapnell, {B. C.} and Y. Inoue and F. Bonella and C. Morgan and S. Jouneau and E. Bendstrup and I. Campo and Papiris, {S. A.} and E. Yamaguchi and E. Cetinkaya and Ilkovich, {M. M.} and Kramer, {M. R.} and M. Veltkamp and M. Kreuter and T. Baba and C. Ganslandt and I. Tarnow and G. Waterer and T. Jouhikainen and {IMPALA Trial Investigators}",
year = "2020",
month = oct,
doi = "10.1056/NEJMoa1913590",
language = "English",
volume = "383",
pages = "1635--1644",
journal = "The New England Journal of Medicine",
issn = "0028-4793",
publisher = "MASSACHUSETTS MEDICAL SOC",
number = "17",

}

RIS

TY - JOUR

T1 - Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis

AU - Trapnell, B. C.

AU - Inoue, Y.

AU - Bonella, F.

AU - Morgan, C.

AU - Jouneau, S.

AU - Bendstrup, E.

AU - Campo, I.

AU - Papiris, S. A.

AU - Yamaguchi, E.

AU - Cetinkaya, E.

AU - Ilkovich, M. M.

AU - Kramer, M. R.

AU - Veltkamp, M.

AU - Kreuter, M.

AU - Baba, T.

AU - Ganslandt, C.

AU - Tarnow, I.

AU - Waterer, G.

AU - Jouhikainen, T.

AU - IMPALA Trial Investigators

PY - 2020/10

Y1 - 2020/10

N2 - BACKGROUND Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

AB - BACKGROUND Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

UR - http://www.scopus.com/inward/record.url?scp=85094220565&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1913590

DO - 10.1056/NEJMoa1913590

M3 - Journal article

C2 - 32897035

AN - SCOPUS:85094220565

VL - 383

SP - 1635

EP - 1644

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 17

ER -