The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy: a systematic review and indirect comparison.
BACKGROUND
Retigabine (RTG) is now approved in Europe and the US for the adjunctive treatment of partial-onset seizures in adults with epilepsy. To support submissions to EU reimbursement authorities, we explored its efficacy and tolerability relative to selected antiepileptic drugs (AEDs).


METHODS
A systematic review was conducted to identify placebo-controlled trials of RTG and selected AEDs approved for use in a similar position in the management pathway of partial epilepsy (eslicarbazepine acetate [ESL], lacosamide [LCM], pregabalin [PGB], tiagabine [TGB] and zonisamide [ZNS]). Using conventional and network meta-analyses as appropriate, we report efficacy and tolerability outcomes for each AED versus placebo and the performance of RTG relative to other AEDs.


RESULTS
Twenty studies met the inclusion criteria: three each for RTG, ESL, LCM, TGB and ZNS; five for PGB. Comparisons comprised 1-5 studies per AED. In the network meta-analysis, RTG was not found to be different from the other AEDs for responder rate (maintenance period), seizure freedom (maintenance period and double-blind period), withdrawals due to adverse events, and incidences of ataxia, dizziness, fatigue and nausea. Differences between RTG and other AEDs were found for a few comparisons, which did not reveal any trends: RTG was associated with a lower responder rate than PGB during the double-blind period, higher withdrawal rate due to any reason than ESL and a higher incidence of somnolence than TGB.


CONCLUSIONS
Findings suggest that the risk/benefit for RTG is similar to that for comparator AEDs. However, results should be interpreted in the context of the limitations of the analyses.
York Health Economics Consortium, Market Square, University of York, Vanbrugh Way, Heslington, York YO10 5NH, UK. marrissa.martyn-stjames@york.ac.uk
Marrissa
M
Martyn-St James
Julie
J
Glanville
Rachael
R
McCool
Steve
S
Duffy
James
J
Cooper
Pierre
P
Hugel
Peter W
PW
Lane
D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects*; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced / Q000453:epidemiology; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D010655:Phenylenediamines / Q000008:administration & dosage* / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine