title: Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action.
abstract: OBJECTIVE
  To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure.
  
  
  OBJECTIVE
  To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures.
  
  
  METHODS
  Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use.
  
  
  METHODS
  Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations.
  
  
  RESULTS
  Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations.
  
  
  CONCLUSIONS
  The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.
authors.affiliation: Truven Health Analytics, Bethesda, Maryland.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Margolis
authors.affiliation: Truven Health Analytics, Santa Barbara, California.
authors.forename: Bong-Chul
authors.initials: BC
authors.lastname: Chu
authors.affiliation: Eisai Inc, Woodcliff Lake, New Jersey.
authors.forename: Zhixiao J
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Eisai Inc, Minneapolis, Minnesota.
authors.forename: Ronda
authors.initials: R
authors.lastname: Copher
authors.affiliation: University of Texas Health Science Center at San Antonio6San Antonio Epilepsy Center of Excellence, South Texas Veterans Health Care System.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Cavazos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000145:classification; D004632:Emergency Medical Services / Q000706:statistics & numerical data; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006296:Health Services / Q000706:statistics & numerical data; D006801:Humans; D007345:Insurance Claim Review; D008297:Male; D055118:Medication Adherence; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C076414:SV2A protein, human; D005680:gamma-Aminobutyric Acid