%0 Journal Article
%T 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.
%A Stevelink R
%A Al-Toma D
%A Jansen FE
%A Lamberink HJ
%A Asadi-Pooya AA
%A Farazdaghi M
%A Cação G
%A Jayalakshmi S
%A Patil A
%A Özkara Ç
%A Aydın Ş
%A Gesche J
%A Beier CP
%A Stephen LJ
%A Brodie MJ
%A Unnithan G
%A Radhakrishnan A
%A Höfler J
%A Trinka E
%A Krause R
%A  
%A Irelli EC
%A Di Bonaventura C
%A Szaflarski JP
%A Hernández-Vanegas LE
%A Moya-Alfaro ML
%A Zhang Y
%A Zhou D
%A Pietrafusa N
%A Specchio N
%A Japaridze G
%A Beniczky S
%A Janmohamed M
%A Kwan P
%A Syvertsen M
%A Selmer KK
%A Vorderwülbecke BJ
%A Holtkamp M
%A Viswanathan LG
%A Sinha S
%A Baykan B
%A Altindag E
%A von Podewils F
%A Schulz J
%A Seneviratne U
%A Viloria-Alebesque A
%A Karakis I
%A D'Souza WJ
%A Sander JW
%A Koeleman BPC
%A Otte WM
%A Braun KPJ
%J EClinicalMedicine
%V 53
%N 0
%D Nov 2022
%M 36467455
%F 17.033
%R 10.1016/j.eclinm.2022.101732
%X <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.