{Reference Type}: Journal Article
{Title}: Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.
{Author}: Stevelink R;Al-Toma D;Jansen FE;Lamberink HJ;Asadi-Pooya AA;Farazdaghi M;Cação G;Jayalakshmi S;Patil A;Özkara Ç;Aydın Ş;Gesche J;Beier CP;Stephen LJ;Brodie MJ;Unnithan G;Radhakrishnan A;Höfler J;Trinka E;Krause R; ;Irelli EC;Di Bonaventura C;Szaflarski JP;Hernández-Vanegas LE;Moya-Alfaro ML;Zhang Y;Zhou D;Pietrafusa N;Specchio N;Japaridze G;Beniczky S;Janmohamed M;Kwan P;Syvertsen M;Selmer KK;Vorderwülbecke BJ;Holtkamp M;Viswanathan LG;Sinha S;Baykan B;Altindag E;von Podewils F;Schulz J;Seneviratne U;Viloria-Alebesque A;Karakis I;D'Souza WJ;Sander JW;Koeleman BPC;Otte WM;Braun KPJ;
{Journal}: EClinicalMedicine
{Volume}: 53
{Issue}: 0
{Year}: Nov 2022
{Factor}: 17.033
{DOI}: 10.1016/j.eclinm.2022.101732
{Abstract}: <B>UNASSIGNED: </B>A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.<BR><B>UNASSIGNED: </B>We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/).<BR><B>UNASSIGNED: </B>Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73).<BR><B>UNASSIGNED: </B>We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools.<BR><B>UNASSIGNED: </B>MING fonds.