Eficácia da miltefosina associada à termoterapia, comparada à miltefosina em monoterapia ou ao uso de antimoniato de meglumina no tratamento da leishmaniose cutânea: ensaio clínico randomizado

Abstract

Introduction: Leishmaniasis, an infectious disease caused by protozoa of the genus Leishmania, affects 98 countries and ranks among the six most relevant diseases due to its deforming potential, particularly in underdeveloped regions. Meglumine antimony (MA), the standard treatment since the 1940s, faces challenges such as toxicity, therapeutic resistance, and low adherence. Alternatives like miltefosine (MF) (approved in India for visceral leishmaniasis in 1998) and thermotherapy have emerged to expand access and reduce adverse effects. Objective: To evaluate whether the combination of MF and thermotherapy is non inferior to MF monotherapy or MA in treating cutaneous leishmaniasis, analyzing cure rates (D90 and D180), healing time, safety, and relapses. Methods: An open-label randomized clinical trial with 27 patients (12–60 years) diagnosed with cutaneous leishmaniasis via detection of L. braziliensis DNA or amastigote forms in histopathology, treated at the Corte de Pedra Reference Center, Bahia. Groups were: G1 (MA): 20 mg/kg/day, 20 days); G2 (MF): 2.5 mg/kg/day, 28 days); G3 (MF): 2.5 mg/kg/day, 21 days + 1 Thermomed® thermotherapy session at 50°C). Results: Treatment failure rates in G1, G2, and G3 were 43%, 30%, and 20%, respectively. Cure rates at day 90 (D90) were 43% (G1), 70% (G2), and 80% (G3), while at day 180 (D180) they reached 57% (G1), 90% (G2), and 80% (G3). Mean healing time was 97 days for G1, 90 days for G2, and 76 days for G3, with a statistically significant difference between G3 and G1 (p = 0.04). Side effects in miltefosine groups included vomiting (70% in G2 and 60% in G3), nausea (40% in G2 and 30% in G3), and diarrhea (20% in both). In G1, 57.1% reported arthralgia and 71.1% myalgia. Secondary infections occurred in 14.2% of G1 and 20% of G3. Conclusions:The combination of MF and thermotherapy demonstrated non inferior effectiveness compared to MF monotherapy and MA in treating cutaneous leishmaniasis. G3 showed higher cure rates and significantly shorter healing time.