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The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia - A review and meta-analysis.
PLoS Negl Trop Dis. 2019 02; 13(2):e0007173.PN

Abstract

BACKGROUND

Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia.

METHODOLOGY/PRINCIPAL FINDINGS

Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6-16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6-100.8) and a PP definite cure rate of 90% (95%CI 81.6-96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common.

CONCLUSIONS/SIGNIFICANCE

Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug's efficacy.

Authors+Show Affiliations

Public Health Department, Médecins Sans Frontières, Amsterdam, The Netherlands. Athena Institute, VU University Amsterdam, Amsterdam, The Netherlands.Public Health Department, Médecins Sans Frontières, London, United Kingdom.Athena Institute, VU University Amsterdam, Amsterdam, The Netherlands.Public Health Department, Médecins Sans Frontières, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

30742620

Citation

Pijpers, Joyce, et al. "The Safety and Efficacy of Miltefosine in the Long-term Treatment of Post-kala-azar Dermal Leishmaniasis in South Asia - a Review and Meta-analysis." PLoS Neglected Tropical Diseases, vol. 13, no. 2, 2019, pp. e0007173.
Pijpers J, den Boer ML, Essink DR, et al. The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia - A review and meta-analysis. PLoS Negl Trop Dis. 2019;13(2):e0007173.
Pijpers, J., den Boer, M. L., Essink, D. R., & Ritmeijer, K. (2019). The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia - A review and meta-analysis. PLoS Neglected Tropical Diseases, 13(2), e0007173. https://doi.org/10.1371/journal.pntd.0007173
Pijpers J, et al. The Safety and Efficacy of Miltefosine in the Long-term Treatment of Post-kala-azar Dermal Leishmaniasis in South Asia - a Review and Meta-analysis. PLoS Negl Trop Dis. 2019;13(2):e0007173. PubMed PMID: 30742620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia - A review and meta-analysis. AU - Pijpers,Joyce, AU - den Boer,Margriet L, AU - Essink,Dirk R, AU - Ritmeijer,Koert, Y1 - 2019/02/11/ PY - 2018/10/31/received PY - 2019/01/20/accepted PY - 2019/02/22/revised PY - 2019/2/12/pubmed PY - 2019/3/21/medline PY - 2019/2/12/entrez SP - e0007173 EP - e0007173 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 13 IS - 2 N2 - BACKGROUND: Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia. METHODOLOGY/PRINCIPAL FINDINGS: Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6-16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6-100.8) and a PP definite cure rate of 90% (95%CI 81.6-96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common. CONCLUSIONS/SIGNIFICANCE: Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug's efficacy. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/30742620/The_safety_and_efficacy_of_miltefosine_in_the_long_term_treatment_of_post_kala_azar_dermal_leishmaniasis_in_South_Asia___A_review_and_meta_analysis_ L2 - https://dx.plos.org/10.1371/journal.pntd.0007173 DB - PRIME DP - Unbound Medicine ER -