Lamotrigine for Generalized Seizures Associated with the Lennox–Gastaut Syndrome

Motté, Jacques; Trevathan, Edwin; Arvidsson, Jfv; Barrera, M. Nieto; Mullens, E.L.; Manasco, Penelope K.

doi:10.1056/nejm199712183372504

Cited by 358 publications

(268 citation statements)

References 25 publications

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“…19,20,25 We assumed that the efficacies of these comparators after 3 months of treatment followed the same trends found for clobazam treatment. Relative clobazam efficacy (i.e., mean reduction in drop seizures) was calculated for 12 months versus 3 months (64.1%/62.1% = 1.03), and for 24 months versus 3 months (52.4%/62.1% = 0.83).…”

Section: Model Structure and Inputsmentioning

confidence: 99%

“…[17][18][19][20] Medical costs were estimated in a retrospective cohort analysis of claims data from a large managed health care plan. 27 Plan participants who had International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for epilepsy (≥ 2 claims) and developmental delay (≥ 1 claim) from January 1, 2007, to September 30, 2009, were identified as LGS patients and included in medical cost analyses.…”

Section: Estimated Costsmentioning

confidence: 99%

“…Key inclusion criteria for this study were as follows: (a) children and adults ages 2 to 54 years with onset of LGS before [18][19][20] that included patients with characteristics similar to those of patients in the CONTAIN trial (i.e., age range, number of drop seizures, seizures not controlled by previous regimens, use of study drug therapy as adjunctive therapy). Felbamate was excluded, as none of its studies were conducted with patients of characteristics similar to those in the clobazam, rufinamide, topiramate, and lamotrigine trials.…”

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confidence: 99%

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Budget Impact Analysis of Antiepileptic Drugs for Lennox-Gastaut Syndrome

Skornicki¹,

Clements²,

O’Sullivan³

2014

JMCP

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BACKGROUND: In October 2011, clobazam was FDA-approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS), a debilitating childhood epilepsy characterized by drop attacks, for patients 2 years and older.OBJECTIVE: To assess the budget impact of adding clobazam to an antiepileptic drug (AED) portfolio containing topiramate, lamotrigine, and rufinamide in a hypothetical, 100,000-member commercially insured health plan.METHODS: Patient characteristics and AED efficacy (decrease in dropseizure frequency) were modeled with clinical data. Medical costs were derived from administrative claims data from a large U.S. managed health plan, with the assumption that 2.3% of drop seizures required medical care. Two-year budget impact was measured. Results were expressed as the overall difference in costs (medical and pharmacy) to a health plan and cost per member per month (PMPM) after addition of clobazam. Analyses of alternative scenarios were performed.RESULTS: With the assumption that 0.04% of the plan population had LGS, adding clobazam to the formulary resulted in cost savings of $98,059 in year 1 and $131,690 in year 2 (savings of $0.08 and $0.11 PMPM, respectively). Analyses of alternative scenarios with lower seizure rates upon discontinuation or greater long-term efficacy for lamotrigine and topiramate did not substantially alter conclusions. The assumption that fewer drop seizures required medical care resulted in a savings of approximately $5,000 per year with clobazam, which suggested that medically attended drop seizures drive costs.CONCLUSIONS: Medically attended drop seizures are a major cost driver for LGS patients. Adding clobazam to a health plan formulary can have a positive overall budget impact through decreased medical costs associated with drop seizures.

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Section: Model Structure and Inputsmentioning

confidence: 99%

Section: Estimated Costsmentioning

confidence: 99%

mentioning

confidence: 99%

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Budget Impact Analysis of Antiepileptic Drugs for Lennox-Gastaut Syndrome

Skornicki¹,

Clements²,

O’Sullivan³

2014

JMCP

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“…In uncontrolled studies,6, 7, 8, 9, 10, 11, 12 70% of patients were considered to be “responders,” defined as having at least a 50% reduction in seizure frequency compared with baseline. In the RCT, however, the proportion of responders in the group randomized to lamotrigine was only 33%, compared with 16% in the group randomized to placebo 13. Thus, the actual gain in responder rate associated with active treatment versus placebo was actually 17% (33% minus 16%).…”

Section: Uncontrolled Studiesmentioning

confidence: 91%

Not all that glitters is gold: A guide to the critical interpretation of drug trials in epilepsy

Perucca

Wiebe

2016

Epilepsia Open

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SummaryClinical trials represent the best source of evidence on which to base treatment decisions. For such evidence to be utilized meaningfully, however, it is essential that results are interpreted correctly. This requires a good understanding of strengths and weaknesses of the adopted design, the clinical relevance of the outcome measures, and the many factors that could affect such outcomes. As a general rule, uncontrolled studies tend to provide misleading evidence as a result of the impact of confounders such as regression to the mean, patient‐related bias, and observer bias. On the other hand, although randomized controlled trials (RCTs) are qualitatively superior, aspects of their execution may still decrease their validity. Bias and decreased validity in RCTs may occur by chance alone (for example, treatment groups may not necessarily be balanced for important variables despite randomization) or because of specific features of the trial design. In the case of industry‐driven studies, bias often influences the outcome in favor of the sponsor's product. Factors that need to be carefully scrutinized include (1) the purpose for which the trial is conducted; (2) potential bias due to unblinding or lack of blinding; (3) the appropriateness of the control group; (4) the power of the study in detecting clinically relevant differences; (5) the extent to which eligibility criteria could affect outcomes and be representative of routine clinical practice; (6) whether the treatments being compared are used optimally in terms of dosing, duration of treatment, and other variables; (7) the appropriateness of the statistical comparisons; (8) the clinical relevance of the outcome measures and whether all key outcome information is reported (for example, responder rates in completers); and (9) potential bias in the way results are presented and discussed. This article discusses each of these aspects and illustrates the discussion with examples taken from published antiepileptic drug trials.

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“…Nevertheless, clinical trials have shown some AEDs to be particularly effective in children with specific epileptic syndromes. For example, vigabatrin is effective in the treatment of infantile spasms, particularly in children with tuberous sclerosis (37)(38)(39), and felbamate and lamotrigine demonstrate efficacy in Lennox-Gastaut syndrome (40,41). As emphasized by Dr. Baram, the brain changes dramatically across the life spans.…”

Section: Introductionmentioning

confidence: 99%