Methods

Randomized, add‐on, double‐blind, placebo‐controlled, multi‐centre trial

Participants

Setting: multi‐centre (Centre Neurologique William Lennox, Ottignies, Belgium; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Epilepsy Center, Kehl‐Kork, Germany)

Number of participants enrolled: 61 (43 in IVIg group, 18 in placebo group)

Sex: 42 male (31 in IVIg group, 11 in placebo group), 19 female (12 in IVIg group, 7 in placebo group)

Mean age (years): IVIg group (24.4 to 26.2), placebo group (18.5)

Mean duration of epilepsy (years): IVIg group (15.33 to 19.44), placebo group (12.54) (data from 58 participants who were included in the seizure frequency analysis)

Race: Caucasian

Types of participants: refractory epilepsy

Inclusion criteria: patients suffering from West syndrome, Lennox‐Gastaut syndrome or an early myoclonic encephalopathy were enrolled as soon as the diagnosis had been made. Patients with any kind of intractable epilepsy were allowed to enter the trial, provided the diagnosis had been made at least 1 year previously and that the seizure frequency was at least 1 per week during the previous 6 months before admission.

Exclusion criteria: patients presenting with any kind of neoplasia, any progressive and/or expansive cerebral disorders (except for Rasmussen syndrome), symptoms of severe renal insufficiency (serum creatinine > 3 mg/100 ml), a known intolerance to blood products, a seropositivity to HIV1 and 2 or a known chromosomal abnormality. Involvement in another clinical trial during the course of the study or the previous 6 months was also excluded.

Interventions

Comparison: IVIg as add‐on treatment to classic AEDs versus add‐on placebo

1. IVIg (BI61011, Behringwerke, Germany): 100 mg/kg, 250 mg/kg, 400 mg/kg

2. Placebo consisted of 2% human albumin solution

Duration of treatment period: 6 weeks

Outcomes

1. 50% or greater reduction in seizure frequency

2. Incidence or severity of adverse effects

3. Global assessment

Notes

Participants with any type of refractory partial or generalized epilepsy were included in the trial

IVIg and placebo groups were not comparable at baseline, including age and median number of daily seizures

All the withdrawals were from IVIg‐treated groups

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

A multi‐centre, randomized trial

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐blinding. Investigators were blinded regarding IVIg versus placebo. External outcome assessors (neurologists) were totally blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3 patients were excluded from the evaluation of seizure frequency: 1 with unaccountable seizures after baseline (100 mg/kg), 1 with continuous partial motor seizures at the beginning and rarely after the IVIg treatment (250 mg/kg) and 1 patient who dropped out (100 mg/kg).

The 1 patient who dropped out (100 mg/kg) was also excluded from the global assessment.

Conclusions remained unchanged for the sensitivity analysis of missing data.

Selective reporting (reporting bias)

Low risk

The main outcome measure for this trial was the reduction of seizure frequencies, and secondary outcome measure was the type and severity of seizures, the interictal status and neurophysiological parameters. 'Global assessment' was used to evaluate several clinical outcomes listed above.

Other bias

Unclear risk

IVIg and placebo groups were not comparable in terms of some baseline data including the mean duration of epilepsy and median number of daily seizures. For patients in the IVIg group, mean duration of epilepsy seemed to be longer than comparison, while median number of daily seizures were less.