MS News Notes: ECTRIMS, Ocrevus, Kesimpta, Epstein-Barr, DMTs
Columnist Ed Tobias comments on the week's top MS news
Here are a few multiple sclerosis (MS) stories that caught my eye last week. Two of them came out of this year’s Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Ocrevus treatment
More than 250,000 people with MS have been treated with the disease-modifying therapy (DMT) Ocrevus (ocrelizumab) since its approval by the U.S. Food and Drug Administration in 2017. Clinical trials have reported that it reduces the rate of MS relapses and eases disability.
The MS News Today story titled “#ECTRIMS2022 – 2-year Ocrevus Effective for Early MS Patients: Data” reports that if treatment with Ocrevus is started in the earliest stages of the disease, even better outcomes and long-term clinical benefits may result. I’m a believer in the hit-it-fast-and-hard theory of MS treatment, and this story reinforces my thoughts on the matter.
Nearly 80% of people with early-stage relapsing-remitting multiple sclerosis (RRMS) show no evidence of disease activity after two years of treatment with Ocrevus according to updated data from the ENSEMBLE Phase 3b trial.
More than 88% of the patients were negative for MRI activity, meaning they had no new or enlarging lesions or lesions with active inflammation. Over 90% also had no relapses or confirmed disability progression at two years.
Ofatumumab injection vs. IV
I was surprised by the story “IV Ofatumumab Reduces Relapses in MS, But Not Better Than Kesimpta.” Though my nonmedical logic tells me that an IV treatment of a medication should work better than an injected one, this study reports otherwise.
It also notes that patients treated with off-label, IV-administered ofatumumab experienced more infusion-related reactions than those treated with other IV-administered, anti-CD20 medications. The case for Kesimpta, which is the brand name of ofatumumab and is administered subcutaneously, was strengthened when, as reported in September in MS News Today, an analysis showed Kesimpta was more cost-effective than most other DMTs. It seems as if it’s a treatment worth discussing with your neurologist.
An intravenous (into-the-vein) formulation of ofatumumab — a disease-modifying therapy for multiple sclerosis sold under the brand name Kesimpta — resulted in a 63% reduction in relapse rates among MS patients, with about 60% remaining relapse-free over the first year of treatment, a recent study in Denmark found.
However, relapse reduction with this formulation was inferior to that seen with the approved formulation of Kesimpta, which is administered subcutaneously, or under the skin.
Another EBV-MS connection
Another story from ECTRIMS adds yet more evidence to support the theory that if scientists can cure the Epstein-Barr virus (EBV), then they have a good shot at curing MS. In this report, “#ECTRIMS2022 – EBV Antibodies Precede Early Nerve Damage Signs,” researcher Daniel Jons, of the University of Gothenburg, Sweden, argues that the presence of EBV antibodies before the appearance of MS “strengthens the theory of EBV infection as a possibly necessary condition for MS development.”
An infection with the Epstein-Barr virus consistently preceded elevations in neurofilament light chain (NfL), an early biomarker of nerve cell damage, in people who went on to develop multiple sclerosis, new data show.
An increase in NfL levels, which is thought to occur before the clinical emergence of MS, was observed about 5–10 years before the onset of disease, whereas antibodies against EBV were detected at high levels as early as 10–15 years before onset. NfL elevations were never detected among the few pre-MS individuals who didn’t develop EBV antibodies.
Stopping a DMT could be risky
There are many reasons why someone might stop receiving a disease-modifying therapy — side effects, lack of efficacy, issues with health insurance coverage, changes in life circumstances such as pregnancy, and more. However, there is little published data on how MS tends to progress after a patient discontinues a DMT.
In “Risk of MS Activity After DMT Stop Greater With RRMS, Younger Age,” Marisa Wexler reports on an analysis of data from 377 people with MS who had been on a DMT for at least two years and then stopped for at least six months. The researchers found “after discontinuation, the presence of relapse was detected in 18.8% and 3.5% in RRMS and SPMS, respectively; and new MRI activity in 22% and 3.5%, respectively.” And the increases were most evident with men younger than 45.
When multiple sclerosis patients stop their disease-modifying treatment, the risk of relapses and disease activity on MRI scans is higher among patients who are younger, have a shorter duration of disease, and have relapsing-remitting MS, a study from Argentina reports.
Male sex and a relapse in the past six months also linked with a greater risk of MRI activity.
Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Multiple Sclerosis News Today or its parent company, Bionews, and are intended to spark discussion about issues pertaining to multiple sclerosis.
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Tom Anderson
Hi Ed- Some alternatives here… Like Ringo sang, “You know it don’t come easy”…. While disease activity showing up on MRI is still the mainstay of evaluating DMT efficacy, cutting edge thinking and evidence continues to point to relapses as a symptom of MS, not MS itself which continues to progress, showing up clinically rather than on MRI (see Barts University MS Blog expert posts, and The MS Selfie, for example). True, hitting it hard and fast seems to deprive MS of some places in the CNS where future damage might accumulate. The trade off with B cell depleters is a normal functioning immune system and a life long acceptance of repeated Covid infections and/or other stuff; so otherwise stay healthy. They are looking at something called BTK which may work as well or better and avoid this pitfall. As to stopping your DMT, there may come a time when treatment makes no significant difference and there are “hints” about that, but certainly early on is not the time to think about it, according to what I’ve read. Finally, there are many ways to look at EBV. Can we come up with a toddler vaccine that prevents infection 100%? What does our covid experience tell us about that? 95% of people are routinely infected, but only one in 300ish of them will get MS. Why is that? A treatment (vs. vaccination) that kills hibernating EBV in B cells might be worth looking into, but I haven’t seen that We still have a ways to go on all this L., but things are much better than they used to be when you and I were diagnosed. Still, start a treatment early and get vaxxed.
Ed Tobias
An interesting read, as always, Tom. I agree about progression that isn't seen on MRIs. I wrote a column, years ago, titled "If my MRI is Stable Why is my MS Getting Worse." I'm also a fan of Dr. G. at BARTS and read his MS Blog. He and think alike but he and others who post there have the expertise that I lack.
Finally, like Dr. G. and friends, I have great hope for the BTK inhibitors. Since, it seems, MS can't exist without EBV if EBV is erased there should be no MS. Two birds with one stone, right?
Mark W
The BTK inhibitors look promising, but it’s probably important to combine them with the antiviral agents, nucleoside antagonists (like Famciclovir) and Highly Active Anti-Retrovial Treatments (like zidovudine combinations). It doesn’t look like these will have the same harmful effects as anti-CD20 antibodies. The treatment goal is likely to shift from NEDA to EBV elimination over the next few years, at last because smouldering progression occurs with NEDA. Prof G suggested something similar years ago. Prof Pender has retired, but his work on anti EBV genetic modulation of T lymphocytes should help achieve this too. If Pharma want to profit from this, they need to get a move on and investigate their HAARTs before generics obtain market dominance.
Ed Tobias
Hi Mark,
Thanks for all of that info. I'm not a scientist, so I don't know much about antivirals or antiretrovials. But, I can certainly see the benefit of combining NEDA with EBV elimination. I think both are needed because, though it seems EBV elimination could eliminate or greatly reduce cases of MS, NEDA would still be needed for those who have already been attacked by MS. Am I missing something?
Ed