@article{3127165,
    title = "Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: Effectiveness, safety, and lowest effective dose",
    author = "Papiris, S.A. and Tsirigotis, P. and Kolilekas, L. and Papadaki, G. and Papaioannou, A.I. and Triantafillidou, C. and Papaporfyriou, A. and Karakatsani, A. and Kagouridis, K. and Griese, M. and Manali, E.D.",
    journal = "Clinical Drug Investigation",
    year = "2014",
    volume = "34",
    number = "8",
    pages = "553-564",
    publisher = "Springer International Publishing",
    issn = "1173-2563",
    doi = "10.1007/s40261-014-0208-z",
    keywords = "CD34 antigen;  recombinant granulocyte macrophage colony stimulating factor;  granulocyte macrophage colony stimulating factor, adult;  aged;  arthralgia;  article;  autoimmune disease;  blood cell count;  bone pain;  burst forming unit E;  clinical article;  clinical protocol;  colony forming unit GM;  dose response;  drug dose reduction;  drug dose regimen;  drug efficacy;  drug safety;  female;  follow up;  hematological parameters;  human;  leukocyte count;  long term care;  lung alveolus proteinosis;  male;  medication compliance;  myalgia;  oxygen desaturation;  priority journal;  relapse;  remission;  retrospective study;  thorax radiography;  treatment outcome;  treatment response;  agonists;  Autoimmune Diseases;  cohort analysis;  middle aged;  Pulmonary Alveolar Proteinosis;  young adult, Adult;  Aged;  Autoimmune Diseases;  Cohort Studies;  Dose-Response Relationship, Drug;  Female;  Follow-Up Studies;  Granulocyte-Macrophage Colony-Stimulating Factor;  Humans;  Male;  Middle Aged;  Pulmonary Alveolar Proteinosis;  Retrospective Studies;  Treatment Outcome;  Young Adult",
    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. © 2014 Springer International Publishing."
}