The Clinical Trial Landscape in Autoimmune Encephalitis: Challenges and Opportunities

Autoimmune encephalitis (AE) is an important cause of neurologic morbidity and mortality. Treatment algorithms are primarily based on observational studies, retrospective series, and expert opinion. Despite clinical improvement with empiric therapy, recovery is often incomplete with a substantial burden of residual neurologic deficits and recurring symptoms. There is a pressing need for higher quality evidence-based therapies. However, designing and conducting clinical trials for patients with rare diseases such as AE has specific challenges, including slow recruitment, suboptimal outcome measures, and inclusivity vs exclusivity of the various disease subtypes. The anticipated knowledge gained from AE clinical trials emphasizes the need to overcome these challenges and support the development of the next generation of clinical trials. Yet, given these challenges, alternative approaches may be required. In this article, we review past and present clinical trials in AE with a focus on studies enrolling patients with neural surface antibodies. We discuss the potential challenges and opportunities inherent to clinical trials in rare diseases and provide an outlook for the field.