King's College London

Dr Laura Mantoan Ritter, Consultant Neurologist at King's College Hospital and Adjunct Reader at King's College London IoPPN, will lead a participating site in a study led by Yale University's Dr. Hirsch (PI) and co-PIs Drs. Gopaul, Eschbach, and Wong.

The group was awarded research funding (>$15 million) by the Patient-Centered Outcomes Research Institute (PCORI) to compare the effectiveness of two immunotherapies in patients with New-Onset Refractory Status Epilepticus (NORSE), including its subtype known as FIRES (Febrile Infection-Related Epilepsy Syndrome).

The study is led by Principal Investigator Dr. Lawrence J. Hirsch (Yale), with Co-Principal Investigators Drs. Margaret Gopaul (Yale), Krista Eschbach (Children’s Hospital of Colorado), and Nora Wong (NORSE Institute), alongside an international team of collaborators. Dr Laura Mantoan Ritter will be the site Principal Investigator at King’s College Hospital.

New-onset refractory status epilepticus (NORSE) is a rare condition characterised by prolonged seizures that do not respond to standard treatments. NORSE occurs in individuals with no prior record of epilepsy or obvious underlying cause.

This study aims to improve outcomes for individuals affected by NORSE through a direct comparison of anakinra and tocilizumab, two promising second-line therapies that are now the current standard of care for unexplained (cryptogenic) NORSE. There is currently no method to help decide between these two options. The current trial will randomise patients to one of these two treatments. The study will involve 33 centres, including 8 international centres in Canada, Europe, and Asia. Yale will be the organising site.

Titled Comparing the effects of anakinra and tocilizumab on outcomes in patients with New-Onset Refractory Status Epilepticus (NORSE), the study will examine how these treatments impact acute seizure control, functional recovery, and long-term neurocognitive outcomes. It will also assess how the timing of administration influences patient outcomes.

Because NORSE is a rare but severe neurological emergency, evidence-based guidance is currently lacking. This project seeks to fill that gap with high-quality, real-world comparative effectiveness data to directly inform clinical practice.

Strong contributions from patients, caregivers, advocacy organisations, and clinicians have shaped and will continue to shape every phase of the project. The NORSE Patient and Family Advisory Board (PFAB) and a diverse Steering Committee were actively involved in the study’s design and will guide its conduct and dissemination.

This study was selected through PCORI’s highly competitive review process, in which patients, caregivers, and other stakeholders join scientists to evaluate proposals. This study represents a meaningful step toward improving care and outcomes for individuals affected by NORSE and their families.

This award has been approved pending completion of a business and programmatic review by PCORI and issuance of a formal award contract.

PCORI is a nonprofit organisation with a mission to fund research designed to provide patients, their caregivers, and clinicians with evidence-based information to make better-informed healthcare decisions.

For more information, please contact:
About this trial: Margaret Gopaul, Ph.D. (Co-PI and Trial Director) – margaret.gopaul@yale.edu or Lawrence J. Hirsch, MD (PI) – lawrence.hirsch@yale.edu

About NORSE and FIRES: https://norseinstitute.org