topiramate and Inflammatory-Bowel-Diseases

Additional medications are needed for inflammatory bowel disease (IBD) as existing therapies are incompletely effective and can be costly and toxic. Preclinical studies suggest that topiramate (an anticonvulsant) may have disease-modifying properties in IBD, but its efficacy in humans is unknown.. To evaluate whether topiramate use is associated with clinical benefit in IBD patients.. We conducted a retrospective cohort study using administrative claims data from the MarketScan databases. Persons with IBD were identified between 2000 and 2010. New users of topiramate were compared with users of other anticonvulsant and anti-migraine medications. The primary outcome was a new prescription for an oral steroid (≥14 days). Secondary outcomes included initiation of biologic agents, abdominal surgery, and hospitalization. Cox proportional hazard modeling was used to adjust for potential confounders.. We identified 773 new users of topiramate and 958 users of comparator drugs. After adjusting for potential confounders, topiramate use was not associated with the primary outcome of steroid prescriptions [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 0.74, 1.73]. Results did not differ significantly by IBD subtype. There was no difference between topiramate users and users of comparator drugs with respect to post-exposure initiation of biologic agents (HR 0.93, 95 % CI 0.39, 2.19), abdominal surgery (HR 1.04, 95 % CI 0.17, 6.41), or hospitalization (HR 0.86, 95 % CI 0.62, 1.19).. In this large U.S. administrative claims study, topiramate use was not associated with markers of IBD flares. These results cast doubt on whether topiramate may be an effective adjunct to current IBD therapy.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Male; Middle Aged; Migraine Disorders; Peripheral Nervous System Diseases; Pharmacoepidemiology; Proportional Hazards Models; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Young Adult

In a pair of papers in this issue of Science Translational Medicine, Butte et al. provide a concrete example of how reinterpreting and comparing genome-wide metrics allows us to effectively hypothesize which drugs from one disease-indication can be repurposed for another disease. The shift toward integrative genome-wide computational approaches has precedence in insightful scalar theories of biological information. Here, we discuss how this recent work in drug repurposing adheres to and takes advantage of the concepts surrounding this information paradigm.

Topics: Animals; Anticonvulsants; Computational Biology; Drug Discovery; Drug Repositioning; Fructose; Humans; Inflammatory Bowel Diseases; Topiramate

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract for which there are few safe and effective therapeutic options for long-term treatment and disease maintenance. Here, we applied a computational approach to discover new drug therapies for IBD in silico, using publicly available molecular data reporting gene expression in IBD samples and 164 small-molecule drug compounds. Among the top compounds predicted to be therapeutic for IBD by our approach were prednisolone, a corticosteroid used to treat IBD, and topiramate, an anticonvulsant drug not previously described to have efficacy for IBD or any related disorders of inflammation or the gastrointestinal tract. Using a trinitrobenzenesulfonic acid (TNBS)-induced rodent model of IBD, we experimentally validated our topiramate prediction in vivo. Oral administration of topiramate significantly reduced gross pathological signs and microscopic damage in primary affected colon tissue in the TNBS-induced rodent model of IBD. These findings suggest that topiramate might serve as a therapeutic option for IBD in humans and support the use of public molecular data and computational approaches to discover new therapeutic options for disease.

Topics: Anticonvulsants; Computational Biology; Fructose; Humans; Inflammatory Bowel Diseases; Reverse Transcriptase Polymerase Chain Reaction; Topiramate