Neurology. 2015 Apr 28; 84(17): 1805–1815. doi: 10.1212/WNL.0000000000001520 PMCID: PMC4424131
Challenges and opportunities in designing clinical trials for neuromyelitis optica
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Brian G. Weinshenker, MD, FRCP(C),corresponding author Gerard Barron, BSc(Hons), Jacinta M. Behne, MA, Jeffery L. Bennett, MD, PhD, Peter S. Chin, MD, MSHS, Bruce A.C. Cree, MD, PhD, MCR, Jerome de Seze, MD, PhD, Armando Flor, MD, Kazuo Fujihara, MD, Benjamin Greenberg, MD, Sayumi Higashi, PhD, William Holt, DO, Omar Khan, MD, Volker Knappertz, MD, Michael Levy, MD, PhD, Angela T. Melia, BSc, Jacqueline Palace, BM, DM, FRCP, Terry J. Smith, MD, Maria Pia Sormani, PhD, Katja Van Herle, MD, Susan VanMeter, MD, Pablo Villoslada, MD, Marc K. Walton, MD, PhD, Warren Wasiewski, MD, Dean M. Wingerchuk, MD, MSc, FRCP(C), and Michael R. Yeaman, PhD, On behalf of the Guthy-Jackson Charitable Foundation International Clinical Consortium
Abstract
Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed. The perceived rarity of NMO has impeded clinical trials for this disease. However, a diagnostic biomarker and recognition of a wider spectrum of NMO presentations has expanded the patient population from which study candidates might be recruited. Emerging insights into the pathogenesis of NMO have provided rationale for exploring new therapeutic targets. Academic, pharmaceutical, and regulatory communities are increasingly interested in meeting the unmet needs of patients with NMO. Clinical trials powered to yield unambiguous outcomes and designed to facilitate rapid evaluation of an expanding pipeline of experimental agents are needed. NMO-related disability occurs incrementally as a result of attacks; thus, limiting attack frequency and severity are critical treatment goals. Yet, the severity of NMO and perception that currently available agents are effective pose challenges to study design. We propose strategies for NMO clinical trials to evaluate agents targeting recovery from acute attacks and prevention of relapses, the 2 primary goals of NMO treatment. Aligning the interests of all stakeholders is an essential step to this end.