Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data

E.A. Ashley; F. Aweeka; K.I. Barnes; Q. Bassat; S. Borrmann; Timothy Davis; P. Deloron; M.B. Denis; A.A. Djimde; J.F. Faucher; B. Genton; P.J. Guérin; K. Hamed; E.M. Hodel; L. Huang; V. Jullien; H.A. Karunajeewa; J.R. Kiechel; P.E. Kofoed; G. Lefèvre; N. Lindegardh; K. Marsh; A. Mårtensson; M. Mayxay; R. Mcgready; C. Moreira; P.N. Newton; B.E. Ngasala; F. Nosten; C. Nsanzabana; S. Parikh; R.N. Price; P. Ringwald; L. Rombo; B. Schramm; C.H. Sibley; K. Stepniewska; J. Ursing; M.V. Vugt; N.J. White; L.J. Workman; P Dahal

doi:10.1186/s12916-015-0456-7

Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data

E.A. Ashley, F. Aweeka, K.I. Barnes, Q. Bassat, S. Borrmann, Timothy Davis, P. Deloron, M.B. Denis, A.A. Djimde, J.F. Faucher, B. Genton, P.J. Guérin, K. Hamed, E.M. Hodel, L. Huang, V. Jullien, H.A. Karunajeewa, J.R. Kiechel, P.E. Kofoed, G. LefèvreN. Lindegardh, K. Marsh, A. Mårtensson, M. Mayxay, R. Mcgready, C. Moreira, P.N. Newton, B.E. Ngasala, F. Nosten, C. Nsanzabana, S. Parikh, R.N. Price, P. Ringwald, L. Rombo, B. Schramm, C.H. Sibley, K. Stepniewska, J. Ursing, M.V. Vugt, N.J. White, L.J. Workman, P Dahal

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Abstract

© 2015 WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group. Background: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. Methods: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. Results: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95 % CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95 % CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (98 % cure rates (if parasitemia

Original language	English
Pages (from-to)	1-19
Journal	BMC Medicine
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s12916-015-0456-7
Publication status	Published - 2015

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Ashley, E. A., Aweeka, F., Barnes, K. I., Bassat, Q., Borrmann, S., Davis, T., Deloron, P., Denis, M. B., Djimde, A. A., Faucher, J. F., Genton, B., Guérin, P. J., Hamed, K., Hodel, E. M., Huang, L., Jullien, V., Karunajeewa, H. A., Kiechel, J. R., Kofoed, P. E., ... Dahal, P. (2015). Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data. BMC Medicine, 13(1), 1-19. https://doi.org/10.1186/s12916-015-0456-7

@article{dac0ac6e08b14a179c01fe0ff521d8d6,

title = "Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data",

abstract = "{\textcopyright} 2015 WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group. Background: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. Methods: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. Results: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95 % CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95 % CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (98 % cure rates (if parasitemia",

author = "E.A. Ashley and F. Aweeka and K.I. Barnes and Q. Bassat and S. Borrmann and Timothy Davis and P. Deloron and M.B. Denis and A.A. Djimde and J.F. Faucher and B. Genton and P.J. Gu{\'e}rin and K. Hamed and E.M. Hodel and L. Huang and V. Jullien and H.A. Karunajeewa and J.R. Kiechel and P.E. Kofoed and G. Lef{\`e}vre and N. Lindegardh and K. Marsh and A. M{\aa}rtensson and M. Mayxay and R. Mcgready and C. Moreira and P.N. Newton and B.E. Ngasala and F. Nosten and C. Nsanzabana and S. Parikh and R.N. Price and P. Ringwald and L. Rombo and B. Schramm and C.H. Sibley and K. Stepniewska and J. Ursing and M.V. Vugt and N.J. White and L.J. Workman and P Dahal",

year = "2015",

doi = "10.1186/s12916-015-0456-7",

language = "English",

volume = "13",

pages = "1--19",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central",

number = "1",

}

Ashley, EA, Aweeka, F, Barnes, KI, Bassat, Q, Borrmann, S, Davis, T, Deloron, P, Denis, MB, Djimde, AA, Faucher, JF, Genton, B, Guérin, PJ, Hamed, K, Hodel, EM, Huang, L, Jullien, V, Karunajeewa, HA, Kiechel, JR, Kofoed, PE, Lefèvre, G, Lindegardh, N, Marsh, K, Mårtensson, A, Mayxay, M, Mcgready, R, Moreira, C, Newton, PN, Ngasala, BE, Nosten, F, Nsanzabana, C, Parikh, S, Price, RN, Ringwald, P, Rombo, L, Schramm, B, Sibley, CH, Stepniewska, K, Ursing, J, Vugt, MV, White, NJ, Workman, LJ & Dahal, P 2015, 'Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data', BMC Medicine, vol. 13, no. 1, pp. 1-19. https://doi.org/10.1186/s12916-015-0456-7

Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data. / Ashley, E.A.; Aweeka, F.; Barnes, K.I. et al.
In: BMC Medicine, Vol. 13, No. 1, 2015, p. 1-19.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: A systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data

AU - Ashley, E.A.

AU - Aweeka, F.

AU - Barnes, K.I.

AU - Bassat, Q.

AU - Borrmann, S.

AU - Davis, Timothy

AU - Deloron, P.

AU - Denis, M.B.

AU - Djimde, A.A.

AU - Faucher, J.F.

AU - Genton, B.

AU - Guérin, P.J.

AU - Hamed, K.

AU - Hodel, E.M.

AU - Huang, L.

AU - Jullien, V.

AU - Karunajeewa, H.A.

AU - Kiechel, J.R.

AU - Kofoed, P.E.

AU - Lefèvre, G.

AU - Lindegardh, N.

AU - Marsh, K.

AU - Mårtensson, A.

AU - Mayxay, M.

AU - Mcgready, R.

AU - Moreira, C.

AU - Newton, P.N.

AU - Ngasala, B.E.

AU - Nosten, F.

AU - Nsanzabana, C.

AU - Parikh, S.

AU - Price, R.N.

AU - Ringwald, P.

AU - Rombo, L.

AU - Schramm, B.

AU - Sibley, C.H.

AU - Stepniewska, K.

AU - Ursing, J.

AU - Vugt, M.V.

AU - White, N.J.

AU - Workman, L.J.

AU - Dahal, P

PY - 2015

Y1 - 2015

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AB - © 2015 WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group. Background: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. Methods: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. Results: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95 % CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95 % CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (98 % cure rates (if parasitemia

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DO - 10.1186/s12916-015-0456-7

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SN - 1741-7015

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JO - BMC Medicine

JF - BMC Medicine

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