D. Ontaneda

Cleveland Clinic Mellen Center for Multiple Sclerosis

Daniel Ontaneda, MD, PhD, is an associate professor of Neurology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a staff member at the Cleveland Clinic Neurological Institute’s Mellen Center for Multiple Sclerosis.

Dr. Ontaneda is the lead principal investigator for a large international multicenter study examining early highly effective versus escalation approaches in multiple sclerosis (DELIVER-MS).He is also the principal investigator for the Central vein Study in MS (CAVS-MS) , a multi-center trial funded  by the NIH/NINDS (U01) examining the role of central vein in the diagnosis of MS. He is also a member of the Executive Steering Committee for the North American Imaging in Multiple Sclerosis Cooperative. Dr. Ontaneda’s research focuses on clinical trials and imaging biomarker. His work is funded by the National Institutes of Health, National Multiple Sclerosis Society, Race to Erase Foundation, and Patient Centered Outcomes Research Institute. Dr. Ontaneda was the recipient of a Sylvia Lawry NMSS clinical Fellowship Award, NIH KL2 Cleveland CTSA career transition award. Dr. Ontaneda received his doctor of medicine from the Pontificia Universidad Católica del Ecuador and Ph.D. in Statistics and Epidemiology at Case Western Reserve University, and Master of Science in Clinical Research from Case Western Reserve University. He completed postdoctoral research fellowship training at Baylor College of Medicine, Houston, Texas. He then completed his neurology residency and a neuroimmunology fellowship at the Cleveland Clinic Foundation.

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Oral Presentation

FC02.02 - Update on the risk estimates of progressive multifocal leukoencephalopathy related to fingolimod

Presentation Number
Presentation Topic
Disease Modifying Therapies – Risk Management
Lecture Time
13:12 - 13:24



Progressive multifocal leukoencephalopathy (PML) is a serious and potentially fatal complication of some multiple sclerosis (MS) disease-modifying therapies, including fingolimod. Precise estimates and risk stratification tools are not available for fingolimod-related PML.


To estimate the global risk of PML in MS patients receiving fingolimod, and to investigate the effect of treatment duration and age on the risk of PML.


The number of PML cases identified from the manufacturer safety database, attributed to fingolimod by expert adjudication (based on criteria published by Berger et al. in 2014) as of 28 February 2020, was compared with the estimated global number of fingolimod-treated patients at risk (overall, by treatment duration, and by assumed age at fingolimod treatment initiation).


It was estimated that approximately 299,600 patients were treated with fingolimod globally as of 28 February 2020, corresponding to >778,900 patient-years (PYs) of exposure. Of the 188 suspected PML cases reported during fingolimod treatment, 37 confirmed cases were clearly attributed to fingolimod through expert adjudication. In 17 cases, PML was attributed to previous natalizumab treatment. The remaining 134 cases either had inadequate information to confirm the diagnosis of PML or were classified as either possible or not PML. The estimated incidence rate was 4.75 (95% confidence interval [CI]: 3.34; 6.55) per 100,000 PYs. The estimated crude incidence was 0.12 (95% CI: 0.09–0.17) per 1,000 patients. The incidence of PML appears to increase with treatment duration and approach a plateau at approximately 0.13 per 1,000 patients during Year 5, after which data were scarce. Incidence of PML appears to increase between 30 and 50 years of age and then stabilize but the exact shape of the relationship with age is uncertain due to wide CIs, underlying assumptions, and other unknown confounding factors. For both treatment duration and age at treatment initiation, the precision of the incidence estimates was low due to the small number of cases.


PML risk associated with fingolimod is low. Although, the estimated risk of fingolimod-associated PML appears to increase with cumulative exposure, the precise pattern of this relationship remains uncertain. There may be an increase in PML risk with increased age at treatment initiation, although the exact pattern of this possible relationship is also uncertain.


Moderator Of 2 Sessions

Hot Topics Sun, Sep 13, 2020
Session Type
Hot Topics
Sun, Sep 13, 2020
Time (ET)
10:15 - 11:00
Parallel Session Fri, Sep 11, 2020
Session Type
Parallel Session
Fri, Sep 11, 2020
Time (ET)
10:15 - 11:45