Comparative efficacy and safety of systemic treatments for cutaneous leishmaniasis: a systematic review and network meta-analysis
Mahmood Fadaie, Sajjad Biglari, Anis Khalafiyan, Maryam Yazdi, Hassan Vahidnezhad, Zabihollah Shahmoradi, Hossein KhanahmadBackground and purpose:
Cutaneous leishmaniasis (CL) is a globally prevalent parasitic disease with various clinical manifestations and therapeutic responses. Despite available systemic therapies, comparative evidence on efficacy and safety remains limited. This systematic review and network meta-analysis (NMA) evaluated systemic therapies for CL.
Experimental approach:
We identified randomized controlled trials (RCTs) assessing systemic therapies through comprehensive searches of MEDLINE, Scopus, Web of Science, Embase, and Google Scholar. Monotherapy and combination regimens were evaluated for efficacy and adverse events. Study quality was assessed using the Cochrane risk of bias tool (RoB2). Heterogeneity was analyzed using Cochran’s Q test and the I 2 statistic (I 2 = 68.8%). Pairwise relative risks (RR) with 95% confidence intervals (CI) were estimated for each treatment versus placebo/control.
Findings/Results:
From 1569 records, 45 RCTs comprising 3331 participants were included in NMA. Meglumine antimoniate combined with allopurinol (RR = 5.61, 95% CI: [3.00-10.46]) and tamoxifen (RR = 5.50, 95% CI: [2.41-12.56]) ranked among the most effective. Subgroup analysis showed allopurinol was more effective in New World CL (NWCL, RR=5.09, 95% CI: [2.03-12.74]) than in Old World CL (OWCL). Meglumine antimoniate combinations showed enhanced efficacy, particularly with allopurinol or tamoxifen in NWCL and allopurinol or pentoxifylline in OWCL. Safety analysis was qualitative due to heterogeneity in adverse event reporting across trials.
Conclusion and implications:
Systemic combination therapies, especially those including meglumine antimoniate, and monotherapies like allopurinol and miltefosine, were highly effective for CL. Further high-quality RCTs with standardized outcome assessments are needed to establish species-adapted, evidence-based clinical guidelines.