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01-08-2014 | Original Research Article

Long-Term Inhaled Granulocyte Macrophage–Colony-Stimulating Factor in Autoimmune Pulmonary Alveolar Proteinosis: Effectiveness, Safety, and Lowest Effective Dose

Authors: Spyros A. Papiris, Panagiotis Tsirigotis, Likurgos Kolilekas, Georgia Papadaki, Andriana I. Papaioannou, Christina Triantafillidou, Anastasia Papaporfyriou, Anna Karakatsani, Konstantinos Kagouridis, Matthias Griese, Effrosyni D. Manali

Published in: Clinical Drug Investigation | Issue 8/2014

Abstract

Background and Objectives

Granulocyte macrophage–colony-stimulating factor (GM-CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis (aPAP). Upon response to short-term treatment, patients are divided into responders and non-responders. The aim of this study was to test the hypothesis that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that attainment of remission permits gradual de-escalation of the dose to the lowest effective safe dose.

Methods

Patients were treated with iGM-CSF 250 μg once a day given 4 days on and 4 days off for as long as necessary (the “as far as it takes” protocol). Upon remission, defined as absence of symptoms, oxygen desaturation <4 % at the walking test, and significant radiographic reduction of the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated. In the case of relapse, the patient was repositioned at the previous effective dose. Patients were investigated at 6-month intervals. To detect hematopoietic effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony-forming-units, and burst-forming-unit erythroid were measured.

Results

Six (five female) patients 43.8 ± 15.7 years of age were treated for 14–65 months and all responded to treatment. Remission was achieved after 25.6 ± 10 months. Three patients maintained remission at their lowest effective dose. Two patients relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM-CSF had no impact on any of the hematological parameters tested.

Conclusions

In aPAP, long-term adherence to the dose schedule permitted remission in all patients. Long-term treatment with iGM-CSF also permitted the definition of lower effective doses, minimizing disease burden and treatment costs safely, since no stimulating activity on hematopoiesis was observed, a fact that is of paramount importance for those aPAP patients needing lifelong treatment.

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Title: Long-Term Inhaled Granulocyte Macrophage–Colony-Stimulating Factor in Autoimmune Pulmonary Alveolar Proteinosis: Effectiveness, Safety, and Lowest Effective Dose
Authors: Spyros A. Papiris
Panagiotis Tsirigotis
Likurgos Kolilekas
Georgia Papadaki
Andriana I. Papaioannou
Christina Triantafillidou
Anastasia Papaporfyriou
Anna Karakatsani
Konstantinos Kagouridis
Matthias Griese
Effrosyni D. Manali
Publication date: 01-08-2014
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 8/2014
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.1007/s40261-014-0208-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Long-Term Inhaled Granulocyte Macrophage–Colony-Stimulating Factor in Autoimmune Pulmonary Alveolar Proteinosis: Effectiveness, Safety, and Lowest Effective Dose

Abstract

Background and Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusions

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