A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil

Paulo R L Machado, Fernanda V O Prates, Viviane Boaventura, Tainã Lago, Luiz H Guimarães, Albert Schriefer, Temis W F Corte, Gerson Penna, Aldina Barral, Manoel Barral-Netto, Edgar M Carvalho, Paulo R L Machado, Fernanda V O Prates, Viviane Boaventura, Tainã Lago, Luiz H Guimarães, Albert Schriefer, Temis W F Corte, Gerson Penna, Aldina Barral, Manoel Barral-Netto, Edgar M Carvalho

Abstract

Background: The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high rate of failure. Miltefosine has proven efficacy for CL caused by L. braziliensis, with a cure rate (CR) of 75%. A combined treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) and miltefosine could increase CR and decrease healing time.

Methods: A randomized, double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M + GM) vs miltefosine and placebo (M + P) vs Sbv in 133 patients with CL caused by L. braziliensis in Bahia, Brazil.

Results: The final CR at 180 days after the initiation of treatment was 44.4% in the Sbv group, 76.6% in the M + P group (P = .003 vs Sbv), and 75.6% in the M + GM group (P = .004 vs Sbv). The median healing time for cure was 102 days for the Sbv group and 60 days for both miltefosine groups (P = .0009). During the 6-month follow-up period, 4 relapses were documented: 1 in the Sbv group, 1 in the M + P group, and 2 in the M + GM group. Mild adverse events occurred in 65% of patients from the Sbv group, 76% and 79% from the M + P and M + GM groups respectively.

Conclusions: Miltefosine is more effective than Sbv for the treatment of CL caused by L. braziliensis in Brazil and accelerates the healing time. Association with GM-CSF does not improve therapeutic outcome.

Clinical trials registration: NCT03023111.

Keywords: Leishmania (V.) braziliensis; GM-CSF; cutaneous leishmaniasis; miltefosine; pentavalent antimony.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Kaplan–Meier curve comparing time to cure in the 3 arms of cutaneous leishmaniasis treatment. Time to cure is the number of days required for complete healing of the ulcers without any sign of clinical activity such as inflammation or raised borders. P = .0009; log-rank test for trend. Abbreviations: GM-CSF, granulocyte macrophage colony-stimulating factor; M, miltefosine; Sbv, pentavalent antimony.

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Source: PubMed

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