NeurologyLive® Top Stories of 2021: Multiple Sclerosis

The world of medical and clinical news was alive with updates on the development of new agents, FDA decisions on promising therapies, and research into better understanding disease pathology and patient care in 2021. As these news stories broke, the NeurologyLive^® team was working tirelessly to provide succinct coverage of the through lines by offering the latest information on announcements and insights from experts in patient care and from the industry to keep the clinical community up to date.

In multiple sclerosis (MS), much of the conversations revolved around the impact of vaccination against and infection with COVID-19, as many patients with MS are on immunosuppressive therapies that were feared may increase their risk of worse outcomes. Additionally, though, 2021 was a landmark year for therapeutic development into progressive forms of the disease and marked the first time a consensus, global set of guidelines were developed in the field.

To offer a look back on some of those stories—many of which are still continuing and will extend into 2022—take a look at some of the coverage provided by the NeurologyLive® team that was most-viewed this year. These stories just scratch the surface of our coverage in MS. You can read more news on MS and demyelinating diseases, hear experts share insight on the top conversations in the field, and learn more about the ongoing discussions on our Multiple Sclerosis clinical focus page.

Click the buttons below to learn more about each story.

1. BTK Inhibitor Fenebrutinib Aims to Tackle Progressive MS in FENtrepid Trial

This August, Alexandra Goodyear, MD, MS, global development lead, Roche, told NeurologyLive^® that “with a Bruton tyrosine kinase [BTK] inhibitor acting on the myeloid cells, we’re hopeful that we can act on the chronic inflammatory processes that seem to be underlying disability progression. Disability progression remains the key unmet need within the MS community. It’s the dual mechanism of action that is really exciting. People have asked, ‘How do we address the compartmentalized inflammation that is pointing to underlying disability progression?’ BTK inhibitors are hitting all the B cells and myeloid cells that are acting on innate immunity.”

Goodyear was speaking to fenebrutinib, an investigational oral BTK inhibitor for the treatment of relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) that, in September of 2020, Roche had announced was being investigated in a new phase 3 clinical trial program. The program included 2 identical phase 3 trials in RMS, FENhance 1 (NCT04586023) and FENhance 2 (NCT04586010), and a separate phase 3 trial in PPMS, FENtrepid (NCT04544449).¹

BTK inhibitors have become a major talking point among the MS community, with a number of therapies making their way through the pipeline, including Sanofi’s tolebrutinib, which demonstrated dose-dependent reduction of gadolinium enhancing lesions among patients with RMS or relapsing secondary progressive MS (SPMS), with it being evaluated in 4 phase 3 trials, GEMINI 1 and GEMINI 2 (NCT04410978; NCT04410991) in patients with relapsing forms of MS, HERCULES (NCT04411641) in non-relapsing SPMS, and PERSEUS (NCT04458051) in PPMS. Additionally, in July, Biogen came into an agreement with InnoCare Pharma to develop orelabrutinib, an oral small molecule BTK inhibitor that is currently being investigated in a global phase 2 study (NCT04711148) in patients with RMS.

2. MRI in Multiple Sclerosis Guidelines Update: North America, Europe Align on New Recommendations

In June, experts in MS from North America and Europe aligned on consensus recommendations for the use of MRI in people with MS. These guidelines—developed by the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) study group; the Consortium of Multiple Sclerosis Centers (CMSC) working group; and the North America Imaging in Multiple Sclerosis (NAIMS) MRI Guidelines working group—address recent advancements in imaging technology and new safety data, among other clinical updates.

A main focus and key update included in the recommendations is the use of standardized MRI protocols for both diagnostic and prognostic purposes, the importance of which was emphasized in the 2017 updates to the McDonald criteria. Previous guidelines from MAGNIMS and CMSC issued in 2015 and 2016, respectively, recommended the use of axial single T2-weighted sequences, dual echo T2-weighted spin echo sequences, axial and sagittal T2-weighted fluid-attenuated inversion recovery (FLAIR), and contrast enhanced axial T1-weighted sequences, preferably at 3T. While these recommendations are still in line with the current McDonald criteria, the new recommendations emphasize the use of 3D acquisition techniques, especially for FLAIR and T1-weighted sequences, as they can both improve lesion detection and contribute to better realignment of anatomic orientation on serial scans.

Then, in late October, at the 2021 CMSC Annual Meeting, one of the authors of the paper, David Li, MD, FRCPC, professor of radiology, associate member in neurology, and director, Multiple Sclerosis/MRI Research Group, University of British Columbia, spoke with NeurologyLive^® on the key points, specifically spoking to the use of a small, portable card that covers the needs for scans to follow the new protocol, its potential to help improve the application of these new guidelines, and how it might better inform patients and physicians about them.

The Standardized MRI Protocol card can be accessed here, and the Spanish version can be accessed here.

3. Pfizer COVID-19 Vaccine Continues to Show Real-World Safety in Multiple Sclerosis

In late July, data from an anonymous survey administered at a tertiary MS center in Israel concluded that the BNT162b2 COVID-19 vaccine (Pfizer) has an overall safe profile for patients with MS and should be further confirmed in larger, prospective studies. These data followed months of discussion about vaccination and disease-modifying therapy (DMT) use in MS amid the COVID-19 pandemic.³ Patients first answered general demographic and disease-related questions and were then questioned on if they received the vaccine, date of vaccination, presence, type of early reactions, and type and timing of new or worsening neurological symptoms following the vaccination.

Then, in October, data presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), suggested that those with MS had stable immunity after infection with SARS-CoV-2 but may see reductions depending on whether they are taking an immunosuppressive DMT, new data suggest. Investigators noted reductions were particularly significant for patients taking anti-CD20 monoclonal antibodies. Also in October, at the 2021 Annual Meeting of CMSC, Anne H. Cross, MD, professor of neurology; and the Manny and Rosalyn Rosenthal – Dr. John Trotter MS Chair in Neuroimmunology, Washington University in St. Louis, presented registry data on the effect of COVID-19 on patients with MS, as well as the impact of individual DMTs on the severity of COVID-19 outcomes. Registry data from a multitude of sources, including the COViMS registry in North America (n = 3452) and European registries (n = 1787), suggest that patients with MS who are older, male, more disabled, and those with comorbidities are likely to develop worse cases of COVID-19 when and if they do contract the infection.

At CMSC 2021, Amit Bar-OR, MD, FRCPC, FAAN, FANA, told NeurologyLive^® that “in terms of the current recommendations—and this is endorsed by the National MS Society Task Force that I've had the privilege of being part of—first of all, individuals living with MS ought to be vaccinated for COVID-19. There is little to suggest any added risk by virtue of having a MS in terms of MS and MS disease activity, and while something rarely bad can happen to any one individual, overall, the risks of the vaccines and people with MS are indistinguishable from the general population and the imperative of being well vaccinated in the context of the pandemic is clearly outweighing any risks.”

REFERENCES
1. Roche expands its multiple sclerosis portfolio with investigational BTK inhibitor fenebrutinib and initiates novel clinical trials for OCREVUS (ocrelizumab). News release. September 9, 2020. Accessed December 21, 2021. https://www.globenewswire.com/news-release/2020/09/09/2090572/0/en/Roche-expands-its-multiple-sclerosis-portfolio-with-investigational-BTK-inhibitor-fenebrutinib-and-initiates-novel-clinical-trials-for-OCREVUS-ocrelizumab.html
2. Wattjes MP, Ciccarelli O, Reich DS, et al; on behalf of the Magnetic Resonance Imaging in Multiple Sclerosis study group, the Consortium of Multiple Sclerosis Centers, and North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group. 2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol. 2021;20(8):653-670. doi:10.1016/S1474-4422(21)00095-8
3. Lotan I, Wilf-Yarkoni A, Friedman Y, Stiebel-Kalish H, Steiner I, Hellman MA. Safety of the BNT162b2 COVID-19 vaccine in multiple sclerosis: early experience from a tertiary MS center in Israel. Eur J Neurol. 2021;28(11): 3742-3748. doi:10.1111/ene.15028