Antiepileptic‑drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy
Sarangi, Sudhir C.
Antiepileptic‑drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy - Vol.54(1), Jan-Feb - Mumbai Wolter Kluwer 2022 - 24-32p.
OBJECTIVES: Antiepileptic‑drug (AED) serum level and inflammatory biomarkers are primarily
monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation
with seizure recurrence (SR) following AED‑tapering has not been established, and this is being
investigated in this study.
MATERIALS AND METHODS: This prospective observational study enrolled persons with
epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure‑free for ≥2 years.
Data regarding seizure episodes, AED‑treatment, and adverse events (using Liverpool Adverse
Event profile [LAEP]‑score) were recorded. Serum AED levels using high‑performance liquid
chromatography and biomarkers levels through enzyme‑linked immunosorbent assay kits were
estimated at AED‑tapering commencement and at 6 months/SR time.
RESULTS: Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29],
and phenytoin [n = 14]), SR occurred in 23.3% during follow‑up (range 12–44 months). PWE
with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than
those with therapeutic or higher levels. Levetiracetam‑treated PWEs with SR have significantly
low AED levels than PWE with no‑SR (P < 0.001). PWE had significantly raised inflammatory
biomarkers (interleukin [IL]‑1 β, tumor necrosis factor [TNF]‑α, IL‑6, and high-mobility group
box protein 1) and decreased IL‑10 than healthy control subjects. SR and no‑SR groups did not
differ significantly in inflammatory markers except for higher IL‑1 β and TNF‑α levels in SR group
(P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow‑up visits without
any difference between SR and no‑SR groups.
CONCLUSION: Low serum AED levels (especially levetiracetam) and raised levels of TNF‑α and
IL‑1 β during tapering commencement had a higher association with SR following AED‑tapering.
PHARMACOLOGY
Antiepileptic‑drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy - Vol.54(1), Jan-Feb - Mumbai Wolter Kluwer 2022 - 24-32p.
OBJECTIVES: Antiepileptic‑drug (AED) serum level and inflammatory biomarkers are primarily
monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation
with seizure recurrence (SR) following AED‑tapering has not been established, and this is being
investigated in this study.
MATERIALS AND METHODS: This prospective observational study enrolled persons with
epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure‑free for ≥2 years.
Data regarding seizure episodes, AED‑treatment, and adverse events (using Liverpool Adverse
Event profile [LAEP]‑score) were recorded. Serum AED levels using high‑performance liquid
chromatography and biomarkers levels through enzyme‑linked immunosorbent assay kits were
estimated at AED‑tapering commencement and at 6 months/SR time.
RESULTS: Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29],
and phenytoin [n = 14]), SR occurred in 23.3% during follow‑up (range 12–44 months). PWE
with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than
those with therapeutic or higher levels. Levetiracetam‑treated PWEs with SR have significantly
low AED levels than PWE with no‑SR (P < 0.001). PWE had significantly raised inflammatory
biomarkers (interleukin [IL]‑1 β, tumor necrosis factor [TNF]‑α, IL‑6, and high-mobility group
box protein 1) and decreased IL‑10 than healthy control subjects. SR and no‑SR groups did not
differ significantly in inflammatory markers except for higher IL‑1 β and TNF‑α levels in SR group
(P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow‑up visits without
any difference between SR and no‑SR groups.
CONCLUSION: Low serum AED levels (especially levetiracetam) and raised levels of TNF‑α and
IL‑1 β during tapering commencement had a higher association with SR following AED‑tapering.
PHARMACOLOGY