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Mefloquine Versus Sulfadoxine–Pyrimethamine for Intermittent Preventive Treatment in Pregnancy: A Joint Analysis on Efficacy and Tolerability

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  • Mère et Enfant Face aux Infections Tropicales (UMR216-MERIT), Institut de Recherche pour le Développement (IRD), Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Inserm, UMR1181, Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Villejuif, France; UMR1181, B2PHI, Institut Pasteur, Paris, France; UMR1181, B2PHI, Université Versailles Saint Quentin, Villejuif, France; Centre INSERM U897–Epidemiologie–Biostatistique, Bordeaux, France; Laboratoire de Parasitologie, Faculté des Sciences de la Santé (FSS), Cotonou, Benin; Centre d′Étude et de Recherche sur le Paludisme Associé à la Grossesse et l′Enfance (CERPAGE), Cotonou, Benin

Since there is no ideal candidate to replace sulfadoxine–pyrimethamine (SP) for intermittent preventive treatment (IPTp), alternatives need to be evaluated on basis of their benefit–risk ratio. We reanalyzed the first Beninese trial on mefloquine (MQ) versus SP for IPTp using a multiple outcome approach, which allowed the joint assessment of efficacy and tolerability. Overall superiority of MQ to SP was defined as superiority on at least one efficacy outcome (low birth weight [LBW], placental malaria, or maternal anemia), non-inferiority on all of them as well as on tolerability defined as cutaneous or neuropsychiatric adverse events (AEs) or low compliance with the treatment. The analysis included 1,601 women. MQ was found to be overall superior to SP (P = 0.004). Performing several sensitivity analyses to handle both missing data and stillbirths provided similar results. Using MQ for IPTp as an example, we show that a multiple outcome analysis is a pragmatic way to assess the benefits/disadvantages of one drug compared with another. In the current context of a lack of antimalarials that could be used for IPTp, such a statistical approach could be widely used by institutional policy makers for future recommendations regarding the prevention of malaria in pregnancy (MiP).

Author Notes

* Address correspondence to Valérie Briand, UMR216–MERIT, Institut de Recherche pour le Développement, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France. E-mail: valerie.briand@ird.fr

Financial support: The trial was supported by the “Fonds de Solidarité Prioritaire” (French Ministry of Foreign Affairs, project number 2006–22); and the “Institut de Recherche pour le Développement”. VB was sponsored by the Fondation pour la Recherche Médicale (grant FDM20060907976), the Fondation de France (Fonds Inkermann), and the Fondation Mérieux.

Authors' addresses: Valérie Briand and Michel Cot, Mère et Enfant Face aux Infections Tropicales (UMR216-MERIT), Institut de Recherche pour le Développement (IRD), Paris, France, and Université Paris Descartes, Sorbonne Paris Cité, Paris, France, E-mails: valerie.briand@ird.fr and michel.cot@ird.fr. Sylvie Escolano and Pascale Tubert-Bitter, Inserm, UMR 1181, Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Villejuif, France, UMR 1181, B2PHI, Institut Pasteur, Paris, France, and UMR 1181, B2PHI, Université Versailles Saint Quentin, Villejuif, France, E-mails: sylvie.escolano@inserm.fr and pascale.tubert@inserm.fr. Valérie Journot, Centre INSERM U897–Epidemiologie–Biostatistique, Bordeaux, France, E-mail: valerie.journot@isped.u-bordeaux2.fr. Achille Massougbodji, Laboratoire de Parasitologie, Faculté des Sciences de la Santé (FSS), Cotonou, Benin, and Centre d'Étude et de Recherche sur le Paludisme Associé à la Grossesse et l'Enfance (CERPAGE), Cotonou, Benin, E-mail: achille.massougbodji@ird.fr.

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