The RIDOSE-MS study investigated whether extending rituximab dosing intervals could maintain efficacy and reduce side effects in relapsing-remitting multiple sclerosis (RRMS).
In this Q&A, we spoke with Prof. Anders Svenningsson, Professor of Neurology at Karolinska Institutet and consultant at Danderyd Hospital, Stockholm, about the background to the RIDOSE-MS trial (NCT03979456), clinical insights on results, what the data reveal about long-term safety and efficacy, and how personalized dosing could shape future anti-CD20 treatment.
My name is Anders Svenningsson, and I’m a Professor of Neurology at Karolinska Institutet and consultant neurologist at Danderyd Hospital in Stockholm. I’ve been working with multiple sclerosis more or less all my life, and since around 2010, my research has focused mainly on rituximab.
In Sweden, we saw the potential of the drug very early on when the first phase II data came out. We started using it long before it became widely known in MS and have now conducted two academic phase III trials. For me, the question has never been about proving efficacy as it’s already well documented, but about understanding how to dose rituximab so that we keep its strong effects while reducing the side effects.
Rituximab results in B-cell depletion lasting for prolonged periods of time leading to increased risk of infection, and sometimes causes severe infections, as well as other potential autoimmune complications. We believe much of this is dose dependent, so my work now is about finding how we can keep the positive effects of rituximab while minimizing the negatives, and how to best monitor patients along the way.
The idea really came from clinical experience. From the start, we used the rheumatology protocol, two 1,000 mg doses, and saw that the effect lasted a long time. In rheumatoid arthritis, patients often notice when disease activity comes back as joint pain, but in MS, renewed activity means a lesion in the central nervous system (CNS), which can leave permanent symptoms. We didn’t want to just “wait and see” in that way.
So, we began using intermittent dosing every six months, initially 1,000 mg, which is roughly equivalent to 600 mg ocrelizumab. After a while, we noticed infections and drops in immunoglobulins, so we reduced the dose to 500 mg every six months. It still worked perfectly well. That’s what led to the RIDOSE-MS trial, to test this more formally and see whether we could stretch the interval even further while maintaining efficacy.
We had already been doing this in clinical practice, but we needed proper randomized controlled data before recommending it more widely. Rituximab is off-label in MS, so we have some freedom to adjust, but we also wanted solid evidence to support what we were seeing day-to-day.
We looked at the usual markers which were relapses, MRI lesions, and disability progression. The outcomes were incredibly stable across the board. Achieving no evidence of disease activity (NEDA-3) over three years shows that extended dosing maintains full efficacy.
What was especially encouraging is how well this matched our clinical experience. We see patients who have been on rituximab for years without any disease activity, either clinically or radiologically. There’s been a lot of talk recently about every patient having “silent progression” early on, but we really don’t see that in most of our early-treated RRMS patients. The vast majority remain stable year after year.
The results were excellent and completely in line with what we expected. The relapse rate was extremely low, and the MRI data followed the same pattern. The confirmed disability worsening rate was also very low, maybe even lower than in other large trials.
To me, this reflects what we see in clinical practice. Patients who start early on rituximab often stay remarkably stable, without new activity or noticeable progression. They just come back each year for their follow-up, and everything looks the same. That’s very reassuring and really underlines how effective the treatment is, even with lower or less frequent dosing.
We were a little disappointed not to see a clearer reduction in infection rates between the two arms, most of the serious infections were COVID-related, so that complicated things. Still, the overall infection rate was very low, which tells us we already have a fairly safe protocol with six-monthly dosing.
The IgG decline was also quite parallel between groups and not statistically significant, but we think there’s still potential to improve safety. It reinforces the idea that we can go even further, either by spacing infusions more or reducing the dose for selected patients.
Our next step is to find the best biomarker to guide this. We believe memory B cells are key, because they’re involved both in MS activity and in protecting against infections. Some patients don’t get their memory B cells back for years after treatment, and those people simply don’t need another infusion. Giving them one on a fixed schedule just increases their risk unnecessarily.
We also saw a small signal for inflammatory bowel disease, which we’d noticed anecdotally before. We’re now running a registry study in Sweden to see if there’s a genuine connection between rituximab and IBD, and if so, how we should manage that clinically.
I think it will influence practice immediately. Based on these data, we can confidently recommend yearly infusions after the first year of treatment instead of every six months. That change alone could reduce side effects and improve convenience for both patients and healthcare teams.
This also has clear implications for ocrelizumab, due to its similar mechanism. I believe you could safely reduce it from 600 mg every six months to 300 mg once a year, which would be a huge improvement in safety. Of course, it needs to be tested formally, but I’m convinced the efficacy would hold.
Ultimately, I think the future lies in individualized dosing, using biomarkers like memory B-cell counts to guide when each patient really needs treatment. Some will need it more often, others much less. That’s how we optimize both efficacy and safety.
To conclude: What we’ve learned over the years is that both the efficacy and side effects of anti-CD20 therapy are really dose dependent. If we refine the intermittent infusion approach and use biomarkers to guide decisions, we can make treatment much more personalised. The goal is simple: keep the high efficacy, reduce the side effects, and make these therapies safer for the long term.
We didn’t see much new this year from the BTK inhibitors, which were a big topic last year, but the concept of treating inflammation inside the CNS remains very interesting. Some newer BTK inhibitors showed better effects on the relapsing phase, while tolebrutinib had more impact on progression, which is fascinating.
I also think anti-CD40 therapy in MS could be very promising, as it targets the interaction between B cells and T cells in a different way.
And then there’s CAR T-cell therapy, which is extremely exciting. If given early, it could have long-term effects on both inflammatory and progressive disease components, acting almost like a reset of the immune system. It’s not ready for routine care yet, it’s too resource-intensive, but it might one day be an alternative to autologous stem-cell transplantation.
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This content has been developed independently by Touch Medical Media for touchNEUROLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Abstract: Svenningsson A, Frisell T, Burman J, et al. Rituximab long-term DOSE trial in Multiple Sclerosis – RIDOSE-MS. A phase 3 trial investigating extended dosing regimen of rituximab in relapsing-remitting MS. Presented at ECTRIMS Congress; September 24-26, 2025; Barcelona, Spain. Late-Breaking Abstract O131.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchNEUROLOGY in collaboration with Anders Svenningsson. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchNEUROLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
Prof. Anders Svenningsson has received grant/research support from the Swedish Medical Research Council.
Cite: Anders Svenningsson. Extending rituximab intervals in MS: Insights from the RIDOSE-MS trial. touchNEUROLOGY. 09 October 2025.
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