Τίτλος:
Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: Effectiveness, safety, and lowest effective dose
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Papiris, S.A.
Tsirigotis, P.
Kolilekas, L.
Papadaki, G.
Papaioannou, A.I.
Triantafillidou, C.
Papaporfyriou, A.
Karakatsani, A.
Kagouridis, K.
Griese, M.
Manali, E.D.
Περιοδικό:
Clinical Drug Investigation
Εκδότης:
Springer International Publishing
Λέξεις-κλειδιά:
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
DOI:
10.1007/s40261-014-0208-z
