Key messages
Immunomodulatory interventions are treatments that target the immune system.
Focal epilepsy is characterised by seizures arising from a specific area of the brain.
Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency in children and adults with focal epilepsy.
What is epilepsy?
Epilepsy is a common neurological condition affecting approximately 50 million people worldwide. Focal epilepsy is characterised by seizures arising from a specific area of the brain. Approximately one-third of patients with epilepsy continue to have seizures despite treatment with antiepileptic drugs. Therefore, the development of effective new therapies for the treatment of epilepsy is of considerable importance. Recently, it has been suggested that the immune system and how it responds to injury may play an important role in this process. As such, immunomodulatory interventions - treatments that target the immune system - may represent a therapeutic approach for focal epilepsy.
What did we want to find out?
We wanted to find out if treatments that target the immune system are better than placebo, in children and adults with focal epilepsy. We also wanted to find out if these treatments are safe.
What did we do?
We searched for studies that looked at treatments that target the immune system in children and adults with focal epilepsy. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
Treatments that target the immune system may be effective in reducing seizure frequency in adults with focal epilepsy. These treatments are more often associated with an increase in adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders, but it is not possible to draw any conclusions about the safety of these agents in children and adults with focal epilepsy.
What are the limitations of the evidence?
We are moderately confident in the evidence due to missing outcome data and imprecise results from the studies. Further high-quality research is needed to fully evaluate the efficacy and tolerability of immunomodulatory interventions.
How up to date is this evidence?
The evidence is up-to-date to November 2021.
Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed.
This is an updated version of an original Cochrane Review published in 2013 (Walker 2013).
Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy.
To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults.
For the latest update, we searched the following databases on 11 November 2021: Cochrane Register of Studies (CRS Web) and Medline (Ovid) 1946 to 10 November 2021. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. We placed no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies.
Randomised placebo-controlled trials of add-on immunomodulatory drug interventions, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. Eligible participants were children (aged over 2 years) and adults with focal epilepsy.
We used standard methodological procedures expected by the Cochrane Collaboration.
We assessed the following outcomes.
1. 50% or greater reduction in seizure frequency.
2. Seizure freedom.
3. Treatment withdrawal for any reason.
4. Quality of life.
5. Adverse effects.
We used an intention-to-treat (ITT) population for all primary analyses, and we presented results as risk ratios (RRs) with 95% confidence intervals (95% Cl).
We included three randomised, double-blind, placebo-controlled trials on a total of 172 participants. All trials included children and adults over two years of age with focal epilepsy. Treatment phases lasted six weeks and follow-up from six weeks to six months. One of the three included trials described an adequate method of concealment of randomisation, whilst the other two trials were rated as having an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in all three trials. All analyses were by ITT. One trial was sponsored by the manufacturer of an immunomodulatory agent and therefore was at high risk of funding bias.
Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency (risk ratio (RR) 2.30, 95% confidence interval (CI) 1.15 to 4.60; 3 studies, 172 participants; moderate-certainty evidence). For treatment withdrawal, there was insufficient evidence to conclude that people were more likely to discontinue immunomodulatory intervention than placebo (RR 1.04, 95% CI 0.28 to 3.80; 3 studies, 172 participants; low-certainty evidence). The RR for adverse effects was 1.16 (95% CI 0.84 to 1.59; 1 study, 66 participants; low-certainty evidence). Certain adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders were more often associated with immunomodulatory interventions. There were little to no data on cognitive effects and quality of life. No important heterogeneity between studies was found for any of the outcomes. We judged the overall certainty of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals.