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

Abstract

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.

Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses

“…Although the studies declared GM-CSF treatment was well tolerated, side effects still occurred in some patients during treatment and follow-up inevitably [17, 23, 27, 28]. As multiple side effects could occur in one patient and the duration of follow-up varies from studies, we defined the side effect rate as the number of side effect events divided by the patient-years of follow-up.…”

Pulmonary alveolar proteinosis: time to shift?

“…More recently, in a study including six patients with aPAP, our group of investigators attempted a different schedule of GM-CSF inhalation, focusing on the effectiveness and safety of a very long-term administration of the drug, in order to obviate non-responders (TABLE 4) [159]. The reasons for the modification of the already published schedules were as follows: the extreme severity of the disease of two patients leaving in the antechamber of intubation, the non-availability of a reliable WLL clinic in Greece and the ineffectiveness of WLL performed in centers Pulmonary alveolar proteinosis Review informahealthcare.com of excellence abroad since two other patients had undergone 64 and 14 WLL procedures, respectively, and still needed more.…”

“…From the above study, it became evident for the first time that: iGM-CSF may prove effective in all, but 'needs time'; 'deescalation' of the inhaled dose is possible after 'remission attainment', maintaining or even further extending improvement; the definition of a 'lowest effective dose' in aPAP patients is achievable, minimizing costs; and finally the eventually needed 'very long-term' administration appears safe because no stimulatory activity on hematopoiesis was observed in any patient [159]. Actually, in an era where new efficacious treatments of aPAP such as iGM-CSF are emerging, the future of what is considered so far as the 'standard of care' for the treatment of PAP should be re-examined.…”

“…Actually, in an era where new efficacious treatments of aPAP such as iGM-CSF are emerging, the future of what is considered so far as the 'standard of care' for the treatment of PAP should be re-examined. Its role in the modification of response to iGM-CSF and in combination treatment strategies should be extensively studied based on the evidence that the partial restoration of the alveolar microenvironment following WLL could facilitate the action of iGM-CSF accelerating time to remission and anticipating dose de-escalation [159,160]. Furthermore, despite evidence for its efficacy in the treatment of aPAP, the administration of iGM-CSF as a sole therapy or in combination with WLL remains still 'off label'.…”

“…6 Inhalational 250 mg/day, days 1-4; 0 mg days 5-8; and upon remission, deescalation to 250 mg/day, days 1-3; 0 mg days 4-8 with further de-escalation to 250 mg/day days 1-2; 0 mg days 3-8 in case of persistence of remission 14-65 months 14-38 months (remission) 6/6 (100%) [159] b.i.d. : Two-times a day.…”