title: Mefloquine Versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment in Pregnancy: A Joint Analysis on Efficacy and Tolerability.
abstract: 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).
authors.affiliation: 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 valerie.briand@ird.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Briand
authors.affiliation: 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.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Escolano
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Journot
authors.affiliation: 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.
authors.forename: Achille
authors.initials: A
authors.lastname: Massougbodji
authors.affiliation: 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.
authors.forename: Michel
authors.initials: M
authors.lastname: Cot
authors.affiliation: 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.
authors.forename: Pascale
authors.initials: P
authors.lastname: Tubert-Bitter
mesh_terms: D000740:Anemia / Q000097:blood / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use*; D001541:Benin; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight / Q000097:blood; D008288:Malaria / Q000517:prevention & control*; D015767:Mefloquine / Q000627:therapeutic use*; D010920:Placenta / Q000469:parasitology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011739:Pyrimethamine / Q000627:therapeutic use*; D050497:Stillbirth; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D015767:Mefloquine; D011739:Pyrimethamine