An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

Author summary Treatment of cutaneous leishmaniasis remains a challenge since the drugs used are quite toxic. Currently, there is a global effort to reduce the morbidity associated with the treatment of this disease and life-threatening complications due to drugs or treatment approaches. Meglumine antimoniate (MA) in different regimens was evaluated in cutaneous leishmaniasis patients in the state of Rio de Janeiro, Brazil. Effectiveness and toxicity were compared among the groups: standard regimen (SR) [intramuscular (IM) MA in the dosage of 10 to 20 mg of pentavalent antimony (Sb5(+))/kg/day]; alternative regimen (AR) [IM MA in the dosage of 5 mg Sb5(+)/kg/day]; and intralesional route (IL) [patients treated with MA through the infiltration of the lesion]. AR and IL regimens demonstrated good effectiveness, with reduced abandonment rate and toxicity. Total adverse events were higher in the SR group, which frequently led to treatment interruptions. AR and IL showed less toxicity especially in CL cases with comorbidities, although SR treatment was more effective than AR and IL regimens. IL was an effective and safe treatment and may be used as a first therapy option as well as a rescue scheme. Background Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. Methodology A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10-20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. Results SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. Conclusions/Significance AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.