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Cochrane Database of Systematic Reviews

Rufinamide add‐on therapy for refractory epilepsy

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DOI:
https://doi.org/10.1002/14651858.CD011772.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 25 April 2018see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Epilepsy Group

Copyright:
  1. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Mariangela Panebianco

    Correspondence to: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

    [email protected]

    [email protected]

  • Hemanshu Prabhakar

    Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India

  • Anthony G Marson

    Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

Contributions of authors

MP was primarily responsible for the writing of this review and completing data extraction and 'Risk of bias' assessments.

AGM provided guidance and manuscript feedback.

HP assessed the studies for eligibility, extracted data and assessed risk of bias.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Institute for Health Research, UK.

    This review was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Epilepsy Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National health Service (NHS) or the Department of Health.

Declarations of interest

MP: none known.

AGM: a consortium of pharmaceutical companies (GSK, Eisai, UCB Pharma) funded the National Audit of Seizure Management in Hospitals (NASH) through grants paid to the University of Liverpool. Professor Tony Marson is part funded by National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care North West Coast (NIHR CLAHRC NWC).

HP: none known.

Acknowledgements

This review update was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Epilepsy Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2020 Nov 08

Rufinamide add‐on therapy for drug‐resistant epilepsy

Review

Mariangela Panebianco, Hemanshu Prabhakar, Anthony G Marson

https://doi.org/10.1002/14651858.CD011772.pub3

2018 Apr 25

Rufinamide add‐on therapy for refractory epilepsy

Review

Mariangela Panebianco, Hemanshu Prabhakar, Anthony G Marson

https://doi.org/10.1002/14651858.CD011772.pub2

2015 Jun 25

Rufinamide add‐on therapy for refractory epilepsy

Protocol

Mariangela Panebianco, Anthony G Marson

https://doi.org/10.1002/14651858.CD011772

Differences between protocol and review

None.

Keywords

MeSH

Medical Subject Headings Check Words

Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Male; Middle Aged;

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Rufinamide versus placebo, outcome: 1.1 50% reduction in seizure frequency.
Figures and Tables -
Figure 4

Rufinamide versus placebo, outcome: 1.1 50% reduction in seizure frequency.

Forest plot of comparison: 1 Rufinamide versus placebo, outcome: 1.3 Treatment withdrawal.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Rufinamide versus placebo, outcome: 1.3 Treatment withdrawal.

Rufinamide versus placebo: 1 Rufinamide versus placebo: 1.4 Adverse effects.
Figures and Tables -
Figure 6

Rufinamide versus placebo: 1 Rufinamide versus placebo: 1.4 Adverse effects.

Comparison 1 Rufinamide versus placebo, Outcome 1 ≥ 50% reduction in seizure frequency.
Figures and Tables -
Analysis 1.1

Comparison 1 Rufinamide versus placebo, Outcome 1 ≥ 50% reduction in seizure frequency.

Comparison 1 Rufinamide versus placebo, Outcome 2 Seizure freedom.
Figures and Tables -
Analysis 1.2

Comparison 1 Rufinamide versus placebo, Outcome 2 Seizure freedom.

Comparison 1 Rufinamide versus placebo, Outcome 3 Treatment withdrawal.
Figures and Tables -
Analysis 1.3

Comparison 1 Rufinamide versus placebo, Outcome 3 Treatment withdrawal.

Comparison 1 Rufinamide versus placebo, Outcome 4 Adverse effects.
Figures and Tables -
Analysis 1.4

Comparison 1 Rufinamide versus placebo, Outcome 4 Adverse effects.

Summary of findings for the main comparison. Rufinamide versus placebo for drug‐resistant focal epilepsy

Rufinamide versus placebo for drug‐resistant focal epilepsy

Patient or population: people with drug‐resistant focal epilepsy

Settings: outpatients

Intervention: rufinamide

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Rufinamide

50% or greater reduction in seizure frequency ‐ ITT analysis

Study population

RR 1.79

(1.44 to 2.22)

1759
(6 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

143 per 1000

256 per 1000
(206 to 317)

Treatment withdrawal

Study population

RR 1.83

(1.45 to 2.31)

1759
(6 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

112 per 1000

205 per 1000
(162 to 259)

Adverse effects: dizziness

Study population

RR 2.52

(1.90 to 3.34)

1295
(3 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

108 per 1000

272 per 1000
(205 to 361)

Adverse effects: fatigue

Study population

RR 1.46

(1.08 to 1.97)

1295
(3 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

112 per 1000

164 per 1000
(121 to 221)

Adverse effects: headache

Study population

RR 1.36

(1.08 to 1.69)

1228
(3 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

196 per 1000

267 per 1000
(212 to 331)

Adverse effects: somnolence

Study population

RR 1.94

(1.44 to 2.61)

1759
(6 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

82 per 1000

159 per 1000
(118 to 214)

Adverse effects: nausea

Study population

RR 1.87

(1.33 to 2.64)

1295
(3 studies)

⊕⊕⊕⊝

Moderate1

RR > 1 indicates outcome is more likely in rufinamide group.

82 per 1000

153 per 1000
(109 to 216)

Adverse effects: vomiting

Study population

RR 2.95

(1.80 to 4.82)

777

(4 studies)

⊕⊕⊝⊝

Low2

RR > 1 indicates outcome is more likely in rufinamide group.

49 per 1000

145 per 1000
(88 to 236)

Adverse effects: diplopia

Study population

RR 4.60

(2.53 to 8.38)

1295

(3 studies)

⊕⊕⊝⊝

Low2

RR > 1 indicates outcome is more likely in rufinamide group.

24 per 1000

110 per 1000
(61 to 201)

*The basis for the assumed risk4(e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ITT: intention to treat; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1. Downgraded once due to risk of bias: unclear methodological information provided for some included studies and all included studies pharmaceutical sponsored.

2. Downgraded once due to imprecision: Wide confidence intervals.

3.Assumed risk is calculated as the event rate in the control group per 1000 people (number of events divided by the number of participants receiving control treatment).

Figures and Tables -
Summary of findings for the main comparison. Rufinamide versus placebo for drug‐resistant focal epilepsy
Comparison 1. Rufinamide versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 ≥ 50% reduction in seizure frequency Show forest plot

6

1759

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [1.44, 2.22]

2 Seizure freedom Show forest plot

1

73

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.36, 4.86]

3 Treatment withdrawal Show forest plot

6

1759

Risk Ratio (M‐H, Fixed, 95% CI)

1.83 [1.45, 2.31]

4 Adverse effects Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Dizziness

3

1295

Risk Ratio (M‐H, Fixed, 95% CI)

2.52 [1.90, 3.34]

4.2 Fatigue

3

1295

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [1.08, 1.97]

4.3 Headache

3

1228

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [1.08, 1.69]

4.4 Somnolence

6

1759

Risk Ratio (M‐H, Fixed, 95% CI)

1.94 [1.44, 2.61]

4.5 Nausea

3

1295

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.33, 2.64]

4.6 Vomiting

4

777

Risk Ratio (M‐H, Fixed, 95% CI)

2.95 [1.80, 4.82]

4.7 Diplopia

3

1295

Risk Ratio (M‐H, Fixed, 95% CI)

4.60 [2.53, 8.38]

Figures and Tables -
Comparison 1. Rufinamide versus placebo