Jiwon Oh, MD, PhD

"There are very few treatments that we have which have shown efficacy in progressive types of MS. Possibly having a molecule that shows an effect across the spectrum of MS would be incredibly helpful. That would mean that this medication could be used at any stage of MS."

As the treatment options for patients with multiple sclerosis (MS) have expanded, one new class of molecules is making promising headway through the pipeline. Bruton tyrosine kinase (BTK) inhibitors, which are designed to reduce B-cell activation, are being evaluated in several ongoing trials, with potential FDA submissions on the horizon. One specific therapy, tolebrutinib (Sanofi), has demonstrated positive results in clinical settings that have featured patients with relapsing MS, secondary progressive MS, and primary progressive MS.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022

, held February 24-26, in West Palm Beach, Florida, data continued to show safety and efficacy in new 18-month results. Led by 

, staff neurologist and medical director, Barlo Multiple Sclerosis Program, St Michaels Hospital, University of Toronto, the findings only add to the palpable buzz within the space about the potential of these therapeutics.

 sat down with Oh to discuss where these inhibitors would fit among other MS medications, if approved. She stressed the need to wait for additional data, but noted that if these agents can show positive results on progressive forms of the disease, there could be immense opportunity to change the field.

REFERENCE
1. MRI, safety, and efficacy outcomes in patients with relapsing MS: 18-month results from the long-term extension study of tolebrutinib. Presented at ACTRIMS Forum 2022; February 24-26; West Palm Beach, FL. Abstract P102

Videos

The staff neurologist and medical director of the Barlo Multiple Sclerosis Program at St Michaels Hospital discussed how investigational BTK inhibitors will be used among an ever-growing MS treatment toolbox. [WATCH TIME: 3 minutes]

Where Tolebrutinib and Other BTK Inhibitors Fit in the MS Treatment Landscape: Jiwon Oh, MD, PhD

"Tolebrutinib is one of the BTK inhibitors that has actually shown evidence of CNS penetration. That’s a big plus. It’s also being looked at in a very comprehensive phase 3 clinical trial program. Two RRMS [trials] and one study of PPMS alone."

Tolebrutinib, an investigational Bruton tyrosine kinase (BTK) inhibitor, once again showed promise in newly presented data at the 

, held February 24-26, in West Palm Beach, Florida. In new phase 2b data, the agent demonstrated a favorable safety profile with low annualized relapse rates (ARRs) at 60-mg doses among patients with relapsing multiple sclerosis (RMS) at 18 months, a much larger time on treatment than the original 16-week trial.

By inhibiting BTK, tolebrutinib is designed to reduce the activation of B-cells, immune cells that play a role in the response that affects the brain and spinal cord in MS. By weeks 48 and 72, when all patients in the lower dose groups switched to 60-mg doses, investigators observed a reduction in new Gadolinium-enhancing lesions. In the original phase 2b study, tolebrutinib demonstrated a dose-dependent reduction in the number of these lesions and was well-tolerated among patients with relapsing-remitting MS or relapsing secondary progressive MS.

, staff neurologist and medical director, Barlo Multiple Sclerosis Program, St Michaels Hospital, University of Toronto, sat down with 

® to provide background on the study, how it was conducted, and the major take-home points clinicians of which should be aware. She also touched on the mechanism of tolebrutinib and why it has proven to be effective to this point.

The staff neurologist and medical director of the Barlo Multiple Sclerosis Program at St Michaels Hospital provided insight on the tolebrutinib’s mechanism of action, and new data presented at ACTRIMS Forum 2022. [WATCH TIME: 4 minutes]

Overview of Tolebrutinib’s Positive 18-Month Data in Relapsing MS: Jiwon Oh, MD, PhD

"It’s a tough sell telling a patient who feels fine that they need to be on a daily regular medication that potentially has side effects. We need phase 3 clinical trial data, and then we need better biomarkers to be able to say, ‘You need to be on treatment. Yes, these treatments have side effects, but it would be helpful for you because you are at a high risk of developing MS.’"

Radiologically isolated syndrome (RIS) is a neurological condition that is characterized by lesions in the central nervous system, specifically the brain, spinal cord, and optic nerves. Historically, RIS has been linked to multiple sclerosis (MS) because of similarities in how brain and spine scans may appear. Being diagnosed with RIS however, does not directly correlate with a diagnosis of MS. Before the introduction of MRI, incidental findings suggestive of MS were only encountered on autopsies, and even after being formally defined for the first time in 2009 by 

 clinicians still are without answers as to why some cases of RIS do and don’t develop into MS.

Researchers including Jiwon Oh, MD, PhD, have thought to use RIS as a way to evaluate the earliest stages of MS, as MS pathophysiologic processes are known to start well before the first symptoms occur. Oh, who is a staff neurologist and medical director of the Barlo Multiple Sclerosis Program at St. Michaels Hospital at the University of Toronto, believes there needs to be an increased push to improve guidelines and management for these patients. Although the syndrome is not common, clinicians have typically taken a trial-and-error approach to treatment with close monitoring.

, February 24-26, in West Palm Beach, Florida, Oh presented on the clinical value of imaging biomarkers within the RIS/MS prodrome. Among the many themes of her presentation, she summarized the current clinical management of RIS and how these biomarkers may be incorporated into routine clinical care. Following the meeting, Oh sat down with 

® to discuss the need to implement new, up-to-date guidelines for this patient population. She also gave her thoughts on whether RIS is understudied and how it can lead to a greater understanding of MS.

REFERENCES
1. Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. 

2009;72(9):800-805. doi:10.1212/01.wnl.0000335764.14513.1a
2. Nakamura M, Morris M, Cerghet M, et al. Longitudinal follow-up of a cohort of patients with incidental abnormal magnetic resonance imaging findings at presentation and their risk of developing multiple sclerosis. 

. 2014;16(3):111-115. doi:10.7224/1537-2073.2013-016

The staff neurologist and medical director of the Barlo Multiple Sclerosis Program at St Michaels Hospital discussed the lack of guidelines for patients with RIS and the research efforts needed going forward to establish them. 

The Need for Guidelines on the Management of Radiologically Isolated Syndrome: Jiwon Oh, MD, PhD

"We found some interesting findings in our patients. Over time, if we can prospectively show that some or a combination of these measures have predictive value, it might be very helpful from a clinical standpoint."

Radiologically isolated syndrome (RIS) refers to an entity in which white matter lesions fulfilling the criteria for multiple sclerosis occur in individuals without a history of clinically demyelinating attack or alternative etiology. It only gained full recognition in 2009, and since then, clinicians have uncovered more about the disease and its relationship to MS using imaging biomarkers. Some experts, including Jiwon Oh, MD, believe RIS represents a valuable opportunity to evaluate the earliest stages of MS prior to the first clinical symptoms occur.

Oh, a staff neurologist, scientist, and medical director of the Barlo Multiple Sclerosis Program at St Michaels Hospital, University of Toronto, recently delivered a speech at the 

, Feb 24-26, in West Palm Beach, Florida, on imaging biomarkers of RIS/MS prodrome. She discussed the current literature on RIS, advanced MRI techniques, clinical management of the disease, and how these imaging biomarkers may be incorporated into routine clinical care.

Following the meeting, she sat down with 

® to outline her speech and why its clinically relevant to the MS community. She also detailed which specific MRI measures clinicians should focus in on, as well as how this type of data should be extracted.

For more coverage of ACTRIMS Forum 2022, 

The staff neurologist and medical director of the Barlo Multiple Sclerosis Program at St Michaels Hospital discussed her presentation at ACTRIMS Forum 2022 involving imaging biomarkers of RIS/MS prodrome. [WATCH TIME: 4 minutes]

Jiwon Oh, MD, PhD

Articles

Where Tolebrutinib and Other BTK Inhibitors Fit in the MS Treatment Landscape: Jiwon Oh, MD, PhD

Overview of Tolebrutinib’s Positive 18-Month Data in Relapsing MS: Jiwon Oh, MD, PhD

The Need for Guidelines on the Management of Radiologically Isolated Syndrome: Jiwon Oh, MD, PhD

Differentiating Radiologically Isolated Syndrome and Multiple Sclerosis With Imaging Biomarkers: Jiwon Oh, MD, PhD

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