Epilepsy effectiveness
rAML, seizure, epilepsy
ADVERSE EFFECTS, INTERACTIONS, ADVERSE EFFECT, EPILEPSY
The effectiveness of epilepsy treatment with everolimus, defined as at least 50% seizure reduction, was observed in one-third of patients with epilepsy in this study. This proportion is similar to the patients treated with a low dose of everolimus in EXIST-3 [This finding might be lower than expected, since most patients also changed ASMs during the study period. Interactions due to concomitant use of enzyme inducers could explain some of the changes, as CYP3A4-mediated metabolism of everolimus is affected by drugs such as carbamazepine, phenytoin, and phenobarbital [In contrast to RCTs studies, it is difficult to know if the seizure frequency reduction is caused by the intervention alone in real world studies [In our study, the proportion of patients with ≥ 50% seizure reduction was higher in Denmark than in Norway.The use of everolimus for epilepsy is restricted in Denmark, to ensure sufficient effect of everolimus, which is an expensive drug with potentially serious adverse effects. Thirty-three and fifty percent seizure reduction, good cooperation, and tolerable adverse effects are required after 4 and 12 months, respectively, to continue treatment. To fulfil these requirements, Danish patients submit seizure diaries for review, and the treating physician submits an evaluation to the Danish Medicines Authorities for documentation after the first treatment year. This is not required in Norway.The observed variability in effectiveness between Norway and Denmark may not reflect a real discrepancy in efficacy, but may be influenced by the requirement to fulfill efficacy criteria in Denmark.Another possible explanation is that patients treated for epilepsy indication were younger at start of treatment in Denmark than in Norway and although the difference were not significant, it is possible that also influenced the difference. In addition, there was not difference in patients with less than 50% reduction between Norway and Denmark.The proportions of patients who reported ≥ 50% seizure reduction varied between 33 and 78% [Patients who started treatment before 2 years did not report a better effect in our study, although seizure reduction was associated with younger age, as also reported previously [The number of ASMs did not decrease under everolimus treatment in our study. The different safety profiles of everolimus compared to other ASMs, gives a higher and different adverse effect load for patients treated with everolimus for epilepsy.In contrast to the results from EXIST-3, which reported higher odds for response in patients treated with high exposure [However, if the efficacy of everolimus is not dose dependent, as it seems in some other studies [No growth or a small reduction in rAML and SEGA lesions might be sufficient to prevent symptoms, whereas a small reduction in seizure frequency might not be as clinically relevant. However, a slight reduction in seizure frequency may make a difference in everyday life for persons with epilepsy [A reasonable effect with regard to seizure reduction and tolerable adverse effects, as requested in Denmark, could, in general, be recommended to continue treatment for the epilepsy indication.