BioSpace has reported on the main preliminary findings of a retrospective study of medical claims data on oral clefts associated with topiramate exposure in utero.  FORTRESS (Fetal Outcome Retrospective TopiRamate ExpoSure Study) identified 1,945 mother-infant dyads exposed to topiramate, either as monotherapy (n=1,740) or in combination with other antiepileptic agents, in the first trimester of pregnancy.  In the monotherapy cohort there were 5 oral clefts for a prevalence of 0.29%; this compared to a rate of 0.16% in a control group of infants born to women who had previously taken antiepileptics but not during the pregnancy (prevalence ratio of 1.88 [95% CI 0.70 - 5.03] for the monotherapy cohort versus the formerly exposed cohort). The company commented that this prevalence ratio is within the recently reported range for topiramate from several large studies. Major congenital malformations are also being evaluated as part of FORTRESS, but the analysis is currently ongoing.

A second control group was also used, consisting of infants of women with similar medical profiles to the total topiramate cohort regardless of prior antiepileptic drug use (similar medical profile cohort; n=13,614).  The prevalence of oral clefts was 0.36% in the total topiramate group, 0.16% in the formerly-exposed control group and 0.07% in the similar medical profile cohort.  Prevalence ratios were 2.36 (95% CI 0.99-5.59) for the total topiramate cohort versus the formerly exposed cohort, and 5.44 (95% CI 2.03-14.61) for total topiramate cohort versus the similar medical profile cohort.

These results are being shared with the FDA for the purposes of the review of a New Drug Application for Qnexa, a controlled-release formulation of low-dose phentermine and topiramate, for obesity.  The FORTRESS findings are based on a claims-only analysis and will only be final when validation is completed (expected in the third quarter of 2012).