Comparing the incidence of acute renal failure in patients with epilepsy exposed to levetiracetam versus other antiepileptic drugs

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  LEVETIRACETAM
• Medical condition to be studied:
  Epilepsy

Population studied

• Short description of the study population:
  US population of patients with an epilepsy diagnosis as defined in Section 9.2.2.1 , with a new prescription of LEV or comparator AEDs, as monotherapy or polytherapy. The following 12 AED monotherapy comparator cohorts will be evaluated in the study: lamotrigine, phenytoin, valproic acid, carbamazepine, gabapentin, topiramate, oxcarbazepine, pregabalin, phenobarbital, zonisamide, lacosamide and ethosuximide. The “monotherapy” analysis includes patients who are AED naïve for at least one year (baseline)and start a new treatment of LEV or of one of the other AEDs listed above. For polytherapy, two cohorts will be evaluated; patients on a LEV-based polytherapy regimen will be compared with a cohort of patients on all other AED polytherapy regimens that do not include LEV as explained in the “polytherapy” definition (see Section 9.3.3.1). These patients are being treated by any AEDs (one or several, except levetiracetam) during the year preceding the index date when a new treatment of AED (different from those given during baseline) is introduced. ; Epilepsy diagnosis Patients will be classified as having an epilepsy diagnosis if they fulfil any of the criteria indicated below: • The presence of ≥ 2 ICD-9-CM codes of 780.39 (seizure symptoms) during separate medical encounters, specifically different dates of care in any medical care venue that are separated by at least 1 day • An occurrence of ≥1 ICD-9-CM code of 780.39 AND ≥1 ICD-9-CM code of 345.xx (excluding 345.3) during separate medical encounters, specifically different dates of care in any medical care venue that are at least 1 day apart, when the first code identified during the baseline period is 780.39 • An occurrence of at least one ICD-9-CM code of 345.xx (excluding 345.3) • Patients with ICD-9-CM code of 345.3 will be required to have ; - an occurrence of ≥2 ICD-9-CM codes of 345.3 separated by at least 30 days ; - or an occurrence of the ICD-9-CM code 780.39 followed by 345.3 code and separated by at least 3
• Age groups:
  • Adolescents (12 to < 18 years)
  • Children (2 to < 12 years)
  • Infants and toddlers (28 days – 23 months)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Epilepsy patients
• Estimated number of subjects:
  3000

Study design details

• Main study objective:
  This study is being conducted compare the incidence rate of acute renal failure among patients exposed to levetiracetam versus other antiepileptic drugs (AEDs) (as monotherapy or polytherapy) to further characterize the risk of acute renal failure in patients treated with AEDs.
• Outcomes:
  The primary outcome of this study is to compare the incidence rate of acute renal failure among patients exposed to levetiracetam (LEV) or comparator antiepileptic drugs (AEDs) (as monotherapy or polytherapy).
• Data analysis plan:
  The modified Poisson regression model with robust variance estimator will be used to estimate the Incidence Rates (IRs) and Incidence Rate Ratio (IRR) of acute renal failure. The crude IR and 95% confidence intervals (CI) will be calculated as the number of new cases per 10,000 person-years of follow-up and reported separately for each Antiepileptic drug (AED) treatment cohort. Crude IRRs and 95% CI based on unweighted samples will be computed to compare the IR of acute renal failure between Levetiracetam (LEV) and each comparator AED cohort. Thereafter, to control for confounding, modified Poisson regression model with robust variance estimator will be constructed based on stabilized Inverse Probability of Treatment Weights weighted samples. The stabilized weights will be applied as exposure weights in the analysis to generate final adjusted effect measure estimates. For each analysis, the comparator cohort will be the reference group.