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Comment
. 2024 Feb 7:13:e91283.
doi: 10.7554/eLife.91283.

Response to comment on 'The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis'

James A Watson  1   2   3 , Robert J Commons  3   4 , Joel Tarning  2   5 , Julie A Simpson  6 , Alejandro Llanos Cuentas  7 , Marcus V G Lacerda  8 , Justin A Green  9 , Gavin C K W Koh  10 , Cindy S Chu  2   11 , François H Nosten  2   11 , Richard N Price  2   3   4 , Nicholas P J Day  2   5 , Nicholas J White  2   5
Affiliations
Comment

Response to comment on 'The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis'

James A Watson et al. Elife. .

Abstract

In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.5 mg/kg) would halve the risk of vivax recurrence by four months. We recommended that clinical trials of higher doses should be carried out to assess their safety and tolerability. Sharma and colleagues at the pharmaceutical company GSK defend the currently recommended adult dose of 300 mg as the optimum balance between radical curative efficacy and haemolytic toxicity (Sharma et al., 2024). We contend that the relative haemolytic risks of the 300 mg and 450 mg doses have not been sufficiently well characterised to justify this opinion. In contrast, we provided evidence that the currently recommended 300 mg dose results in sub-maximal efficacy, and that prospective clinical trials of higher doses are warranted to assess their risks and benefits.

Keywords: Plasmodium vivax malaria; epidemiology; global health; haemolysis; human; infectious disease; microbiology; radical cure; tafenoquine.

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Conflict of interest statement

JW, RC, JT, JS, AL, ML, CC, FN, RP, ND, NW No competing interests declared, JG, GK Former employee of GSK; shareholder in GSK

Figures

Figure 1.
Figure 1.. Hypothetical example showing why the Gini criterion does not lead to a split which is clinically relevant in this context.
Under this data generating process, the optimal split for the Gini criterion is at x=0, corresponding to a probability of 0.5 that y=1.
See this image and copyright information in PMC

Comment on

References

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