Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment

被引:37
作者
Aicua-Rapun, Irene [1 ,2 ]
Andre, Pascal [2 ,3 ]
Rossetti, Andrea O. [1 ,2 ]
Ryvlin, Philippe [1 ,2 ]
Hottinger, Andreas F. [1 ,2 ]
Decosterd, Laurent A. [2 ,4 ]
Buclin, Thierry [2 ,3 ]
Novy, Jan [1 ,2 ]
机构
[1] Lausanne Univ Hosp, Vaud Univ Hosp Ctr, Neurol Serv, Dept Clin Neurosci, Lausanne, Switzerland
[2] Univ Lausanne, Lausanne, Switzerland
[3] Lausanne Univ Hosp, Vaud Univ Hosp Ctr, Serv Clin Pharmacol, Lausanne, Switzerland
[4] Lausanne Univ Hosp, Vaud Univ Hosp Ctr, Lab Clin Pharmacol, Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
LONG-TERM RETENTION; SERUM-LEVELS; REFRACTORY EPILEPSY; PLASMA-LEVELS; ILAE-COMMISSION; SEIZURE; LEVETIRACETAM; LAMOTRIGINE; TOPIRAMATE; CARBAMAZEPINE;
D O I
10.1002/ana.25641
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy. Methods We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints. Results A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm, p = 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit. Interpretation This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2019
引用
收藏
页码:22 / 29
页数:8
相关论文
共 50 条
[1]   Characteristics of a large population of patients with refractory epilepsy attending tertiary referral centers in Italy [J].
Alexandre, Veriano, Jr. ;
Capovilla, Giuseppe ;
Fattore, Cinzia ;
Franco, Valentina ;
Gambardella, Antonio ;
Guerrini, Renzo ;
La Briola, Francesca ;
Ladogana, Marianna ;
Rosati, Eleonora ;
Specchio, Luigi Maria ;
Striano, Salvatore ;
Perucca, Emilio .
EPILEPSIA, 2010, 51 (05) :921-925
[2]  
Andre P, 2015, EPILEPTOLOGIE, V32, P78
[3]   ANTI-CONVULSANT SERUM LEVELS ARE USEFUL ONLY IF THE PHYSICIAN APPROPRIATELY USES THEM - AN ASSESSMENT OF THE IMPACT OF PROVIDING SERUM LEVEL DATA TO PHYSICIANS [J].
BEARDSLEY, RS ;
FREEMAN, JM ;
APPEL, FA .
EPILEPSIA, 1983, 24 (03) :330-335
[4]  
Bentué-Ferrer D, 2010, THERAPIE, V65, P233, DOI [10.3109/13651501.2010.482669, 10.2515/therapie/2010029]
[5]  
Besag Frank M., 1998, Epilepsia, V39, P131
[6]   CLINICAL AND ELECTROENCEPHALOGRAPHIC CORRELATIONS WITH SERUM LEVELS OF DIPHENYLHYDANTOIN [J].
BUCHTHAL, F ;
SVENSMARK, O ;
SCHILLER, PJ .
ARCHIVES OF NEUROLOGY, 1960, 2 (JUN) :624-630
[7]  
Cappellari AM, 2015, THER DRUG MONIT, V37, P285, DOI 10.1097/FTD.0000000000000144
[8]   Lamotrigine serum levels: Ceiling effect in people with epilepsy in remission? [J].
D'Anto, Jennifer ;
Wnuk, Wlodzimierz ;
Rossetti, Andrea O. ;
Decosterd, Laurent A. ;
Buclin, Thierry ;
Novy, Jan .
EPILEPSY & BEHAVIOR, 2017, 74 :41-44
[9]   Antiepileptic drug use in seven electronic health record databases in Europe: A methodologic comparison [J].
de Groot, Mark C. H. ;
Schuerch, Markus ;
de Vries, Frank ;
Hesse, Ulrik ;
Oliva, Belen ;
Gil, Miguel ;
Huerta, Consuelo ;
Requena, Gema ;
de Abajo, Francisco ;
Afonso, Ana S. ;
Souverein, Patrick C. ;
Alvarez, Yolanda ;
Slattery, Jim ;
Rottenkolber, Marietta ;
Schmiedl, Sven ;
Van Dijk, Liset ;
Schlienger, Raymond G. ;
Reynolds, Robert ;
Klungel, Olaf H. .
EPILEPSIA, 2014, 55 (05) :666-673
[10]  
Decosterd LA, 2015, Epileptologie, V32, P85