(79) Efficacy and Safety of Amphotericin B and Oral Miltefosine Combination in Patients with Visceral Leishmaniasis: A Systematic Review and Meta Analysis

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 753

Presenting Author(s)

Christy Thomas
– National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Guwahati, Assam, India

Co-Author(s)

Mandava Satish
– NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH (NIPER), Hajipur, India
Krishna Undela, MPharm, PhD
– Assistant Professor, National Institute of Pharmaceutical Education and Research,Guwahati, Guwahati, Assam, India

Background: Leishmaniasis is one of the most neglected tropical diseases. The disease has more than one clinical form, among them visceral form is considered fatal if left untreated. According to WHO, recommended treatment regimens for Visceral Leishmaniasis involve a combination of the most widely used Amphotericin B and the only available oral drug Miltefosine. However, the safety and efficacy of this combination remain in conflict.

Objectives: To assess the efficacy and safety of Amphotericin B and oral Miltefosine combination in patients with Visceral Leishmaniasis.

Methods: A thorough literature search was performed in PubMed, Cochrane CENTRAL, and Google Scholar from the inception to 31st October 2021. A combination of keywords, MeSH terms, and entry terms on Visceral Leishmaniasis, Amphotericin B, and Miltefosine was used in combination with Boolean operators. All randomized controlled trials (RCTs) investigating the efficacy (initial and definite cure, Reinfection, and Post Kala-Azar Dermal Leishmaniasis (PKDL)) and safety (adverse events and high creatinine) of Amphotericin B and oral Miltefosine combination on Visceral Leishmaniasis in comparison with placebo or active comparator were included in the study. The Fixed or Random-effects model was used based on the heterogeneity identified by using the I² statistic and Cochran's Q test.

Results: Out of 259 non-duplicate RCTs identified through database searching, a total of 8 high-quality studies (Jadad score ≥3), with 3,715 patients were included in this study. Amphotericin B and oral Miltefosine combination showed a significantly lesser incidence of PKDL (OR: 0.62; P=0.01) and high creatinine (OR;0.57 P=0.01) compared to the control group. There was no significant difference between groups in terms of definite cure (OR: 1.05; P=0.87), initial cure (OR:0.77; P=0.32), reinfection (OR:1.34; P=0.19) and adverse events (OR:1.21; P=0.40).

Conclusions: This systematic review and meta-analysis identified a significant association between Amphotericin B and oral Miltefosine combination and efficacy outcomes such as the incidence of PKDL and safety outcomes such as high creatinine. Non-significant results may be due to lower population size and a smaller number of outcomes; hence there is a need for large and long-term studies to address these issues further.