Clinical Trial of IVIG in LGI1/CASPR2 Encephalitis

Dr. Sean Pittock and his group at Mayo Clinic Rochester recently completed a clinical trial that was co-sponsored by the AE Alliance. The study evaluated IVIG treatment in patients with autoimmune epilepsy who fail to benefit from standard epilepsy medications and/or for those where corticosteroids are not considered a treatment option.

Last week, in a webinar conducted as a part of our launch of the AEA Research Network, Dr. Pittock, shared that a patient of his suffering from LGI1 autoimmune epilepsy and who could not receive corticosteroid treatment because of diabetes was denied IVIG treatment. The patient had a seizure at home and developed severe brain injury as a result of inadequately treated epilepsy. This situation led Dr. Pittock to design this trial; to present an alternative treatment option to corticosteroids and to make it easier to receive insurance coverage for IVIG for those that aren’t able to have corticosteroid treatment for autoimmune epilepsy.

This first randomized, double-blind placebo-controlled trial evaluated the efficacy of IVIG in reducing seizure frequency in LGI1 and CASPR2 encephalitis patients. The doctors contacted 594 patients, of which only 17 met the criteria and were entered into the study. One of the requirements of this study was not having received prior immunotherapy, which was the case for the majority of patients in the initial group.

Another challenge in attracting patients for this study was logistical – patients had to come to Mayo Clinic Rochester to participate. The treatment time was five weeks; Pittock’s group didn’t believe it ethical to withhold the placebo group without immunotherapy for any longer than that. A little over a year into the trial, the group led by Dr. Sarosh Irani published a paper that found steroids to be the mainstay of treatment for LGI1 encephalitis and concluded that a delay in immunotreatment translated into poorer cognitive outcomes. This delay, coupled with the difficulty of attracting new patients, led the group at Mayo Clinic to stop the study.

Despite these challenges and limitations, 75% of patients (all LGI1), in the IVIG group experienced more than a 50% reduction in seizure frequency (some patients had more than 60 seizures per day at the start of the trial), compared to 22% in the placebo group. A trend towards more positive cognitive outcomes (stable and improved thinking) was observed in the IVIG group, compared to the placebo group, although there was no statistical difference. Of the IVIG group, 25% achieved seizure freedom by the end of the trial.

This study is especially important for patients in whom corticosteroids are contraindicated or for those not responding to corticosteroid therapy. The data supports the consideration of IVIG as a therapeutic option in these cases and may be supportive in obtaining insurance approval for IVIG.

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