Welcome to this special ECTRIMS update!
In this summary, I’ll walk you through seven new studies that shed light on how multiple sclerosis (MS) treatment is evolving — from safety signals and infection risks to real-world practice shifts and the rise of personalized, data-driven care.
Here’s what you’ll find inside:
Rituximab: How often late-onset neutropenia (LON) really occurs and who’s most at risk.
Ocrelizumab: What factors increase the chance of serious infections — and what that means in everyday care.
Early high-efficacy treatment: Why data from four countries all point to the same message — starting strong matters.
Memory B-cell recovery: What happens to your immune system on long-term ocrelizumab and why extended dosing might be safe.
Cancer risk signals and prevention: What real-world pharmacovigilance tells us, and why HPV vaccination remains essential.
TEMPOS (France): How MS treatment patterns have shifted massively toward early anti-CD20 use — with ofatumumab on the rise.
AI decision tool: A new machine-learning model that helps predict who can safely stop DMT — a first step toward personalized treatment discontinuation.
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Late-onset neutropenia in rituximab therapy for multiple sclerosis – results from a Swedish cohort
Presenter: Dr. Susanna Hallberg, Danderyd Hospital & Karolinska Institutet (Sweden)
Rituximab (RTX) is a highly effective B-cell–depleting therapy used to treat many people with multiple sclerosis (pwMS), especially in Scandinavian countries. While most tolerate it well, a rare side effect called late-onset neutropenia (LON) has raised clinical interest. This means that, months after treatment, the number of neutrophils — a type of white blood cell that helps fight infection — can drop temporarily. Understanding how often this happens, and in whom, helps neurologists keep patients safe while maintaining the benefits of therapy.
Study design
Dr. Susanna Hallberg and her team analyzed 2,686 people with MS treated with rituximab in Sweden. About one-third (31 %) had never received a prior disease-modifying therapy (DMT). Among those previously treated, the most common DMTs were injectables (23 %), natalizumab (20 %), and fingolimod (7.6 %).
The average age of participants was 42 years, and most were women (around 69 %). The median time from the first rituximab infusion to the lowest neutrophil count (“nadir”) was about 1.5 years (531 days). On average, patients had received a total rituximab dose of roughly 4,850 mg.
Key findings
Late-onset neutropenia was seen in about 6 % of all participants — that’s 165 out of 2,686 people treated with rituximab.
Most cases were mild and temporary, meaning the white blood cell count dropped slightly but caused no symptoms.
Only about 1 % of patients developed a more serious drop that could increase the risk of infection.
Among those with stronger reactions, nearly half (48 %) did experience an infection, and seven people needed hospital treatment. The good news:
➡️ Everyone recovered fully, thanks to timely care with antibiotics or medications that boost white blood cell production.
Recurrent and fluctuating patterns
Some people had recurrent or fluctuating episodes of neutropenia — a pattern also seen in other autoimmune diseases and with other anti-CD20 therapies such as ofatumumab or ocrelizumab. Around one quarter (21–29 %) experienced repeated events, though most remained mild.
Predictors of risk
Using logistic regression analysis, the team found that the likelihood of developing LON was associated with:
Younger age
Previous natalizumab treatment (odds ratio ≈ 2.4)
Treatment center differences
For more severe LON (grades 3–4), additional risk factors included:
Obesity (OR ≈ 2.15)
Prior natalizumab exposure (OR ≈ 2.87)
Why this matters for people with MS
While LON remains uncommon, it’s important for anyone on rituximab (or similar therapies) to be aware of it. Regular blood tests and communication with your healthcare team help detect any abnormalities early. The study shows that even when neutropenia occurs, outcomes are generally good, and patients recover fully.
Dr. Hallberg concluded that late-onset neutropenia is a rare but manageable complication of anti-CD20 therapy. Identifying risk factors such as prior natalizumab use or obesity can guide clinicians in personalizing monitoring plans — helping pwMS stay safe while benefiting from one of the most effective treatments currently available.
Risk factors for serious infection in MS treated with Ocrelizumab
Presenter: Dr. Yao Zhang (China), Queen Mary University of London (UK), on behalf of the OPTIMISE:MS study group
Ocrelizumab (OCR) is a widely used, highly effective treatment for relapsing and progressive forms of multiple sclerosis. It works by targeting B cells, part of the immune system involved in MS activity. Like rituximab, it belongs to the group of anti-CD20 therapies.
While these medications can strongly reduce relapses and disease activity, they also slightly lower the body’s immune defenses. That’s why researchers continue to study the risk of serious infections, especially as more people use ocrelizumab long term.
Study goal
The OPTIMISE:MS project – a large, real-world study across 13 UK centers – set out to identify which factors increase the risk of serious infections among people with MS treated with ocrelizumab.
Who took part
The study included 735 people with MS (about two-thirds women, average age 42).
Most participants (over 90 %) had relapsing-remitting MS, and nearly half had never received any prior MS therapy before starting ocrelizumab.
The average follow-up time was a little over three years.
What counted as a “serious infection”?
Researchers defined it as an infection requiring hospital admission, intravenous treatment, or an extended hospital stay — not just a mild cold or urinary tract infection that clears up quickly.
Key results
During the study, 261 serious infections occurred in 208 people — that’s about 28 % of participants.
Most infections affected:
the respiratory tract (lungs and airways) – 15 %,
the urinary tract – 7 %,
and a small number involved the skin or digestive system.
That means around 7 out of 10 people on ocrelizumab did not experience any serious infection at all.
Who was at higher risk?
The research team identified several factors that made serious infections more likely:
Age over 50 when starting ocrelizumab
Female sex
Having a relapse during treatment
Previous use of another MS therapy (DMT)
Having had an infection before starting ocrelizumab
When these factors were analyzed together, the strongest predictors were:
➡️ Being 50 years or older
➡️ Having had an infection before starting OCR
➡️ Experiencing relapses during treatment
These findings suggest that people who already have a higher “infection burden” or immune system stress may be more vulnerable once B-cell therapy begins.
Why this matters for people with MS
Ocrelizumab remains a highly effective and generally well tolerated therapy, and it continues to show excellent results in reducing relapses and slowing progression.
But as this study highlights, monitoring matters — especially for older adults, women, and anyone with prior infections or active relapses.
Regular check-ups, vaccination updates, and open communication with the care team can help prevent complications and ensure that the benefits of treatment far outweigh the risks.
Dr. Zhang concluded that this kind of real-world data helps personalize MS therapy — supporting vigilant infection monitoring and smarter long-term strategies for people using anti-CD20 treatments.
Stronger Together: Early High-Efficacy Treatment in Multiple Sclerosis – Evidence from Four Countries
Presenter: Dr. Dominika Stastná, General University Hospital in Prague (Czech Republic)
Why this study matters
For people newly diagnosed with multiple sclerosis, one of the biggest treatment decisions is when to start a highly effective disease-modifying therapy (HE-DMT). Should treatment begin with a strong therapy right away, or is it safer to start with a milder option and escalate later if needed?
Real-world studies have already shown that early HE-DMT can reduce relapses and slow disability, but results have varied from country to country. Dr. Dominika Stastná and colleagues wanted to find out whether the benefit of early treatment is truly universal.
A collaboration across four nations
The team combined data from Sweden, Denmark, Australia, and the Czech Republic using advanced Bayesian statistics – a method that merges data from different studies to strengthen conclusions. The registries included thousands of people with relapsing MS who started therapy between 2013 and 2018, with follow-up periods of up to eight years.
What they compared
They looked at two treatment strategies:
Early high-efficacy DMT – starting a powerful therapy as the first MS treatment.
Platform DMT – starting with lower-efficacy medication first.
The outcomes they measured included:
Relapse rates
Time to confirmed disability worsening (6-month CDW)
Levels of disability (EDSS 3 and 4)
Chances of disability improvement (6-month CDI)
Key results
Across all four countries, the pattern was clear and consistent:
Early high-efficacy treatment reduced the risk of disability worsening by 44 %.
It also led to significantly fewer relapses and a greater chance of improvement.
These benefits were seen in every participating country – regardless of healthcare system or patient population.
For example, in the Australia vs. Czech Republic comparison, starting high-efficacy therapy first was linked to:
64 % lower risk of confirmed disability worsening,
62 % fewer relapses, and
higher chance of measurable improvement.
When all national data were combined, Bayesian models confirmed the same result:
Early HE-DMT clearly outperformed traditional step-up therapy across all outcomes.
What this means for people with MS
This study provides some of the strongest international real-world evidence yet that starting effective therapy early makes a lasting difference. Beginning strong doesn’t mean taking unnecessary risks — it means giving yourself the best chance to stay stable and independent for longer.
Dr. Stastná closed with a quote from Louis Pasteur:
“Science knows no country, because knowledge belongs to humanity.”
And her message to the MS community echoed that spirit: collaboration across nations strengthens the evidence that early action matters – and that together, we can improve the future of MS care.
How Ocrelizumab Influences Memory B Cells Over Time
Presenter: Dr. Giulio Disanto, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano
Why this study matters
Ocrelizumab (OCR) is a highly effective MS treatment that works by targeting B cells, a type of immune cell that plays a key role in MS inflammation. It’s approved for both relapsing and progressive forms of multiple sclerosis.
While ocrelizumab can dramatically reduce relapses and slow progression, its effect on B-cell recovery after each infusion is still being explored — especially when people stay on the medication for many years. Dr. Giulio Disanto’s study looked closely at how memory B cells (the long-lived B cells involved in immune “memory”) return after treatment and how this might guide extended dosing intervals.
Background
Ocrelizumab causes a prolonged depletion of B cells (the immune cells marked by CD20). This strong suppression helps control MS activity, but if B-cell recovery is too slow, it might affect the immune system’s ability to respond to infections or vaccines.
Dr. Disanto’s group in Lugano examined how cumulative exposure — meaning the total amount of ocrelizumab a person has received over time — influences how quickly memory B cells come back after treatment.
They also aimed to explore whether age, sex, or body weight influence this recovery and whether extended interval dosing (EID) – giving infusions less often – might still keep MS under control.
Study design
Single-center study at the MS Center in Lugano, Switzerland.
101 participants (74 with relapsing MS, 27 with progressive MS).
Median treatment duration: 4.1 years.
Researchers collected 1,369 blood samples to track how B cells returned after each infusion.
They compared:
Standard dosing: every 6 months.
Extended interval dosing (EID): infusion delayed until memory B cells reappeared (≥1 cell/µl).
Main findings
🧬 B-cell recovery
The interval between infusions averaged 6.2 months for standard dosing and 9.8 months for EID (some patients up to 24 months).
Older age and male sex were linked to slower B-cell repopulation.
Weight did not affect recovery.
Higher cumulative OCR dose slowed memory B-cell (CD19+CD27+) return.
In short:
The more ocrelizumab a person had received overall, the longer it took for memory B cells to come back.
💉 Clinical stability
Even with these longer intervals, the patients remained largely stable:
Only 2 % had relapses.
MRI activity was low (8 patients showed new lesions).
Disability progression (EDSS) occurred in 18 %, mostly in those with progressive MS.
🧫 Immunoglobulins (antibodies)
Levels of IgG and IgM antibodies (important for immune defense) gradually decreased over time, but:
Severe deficits were rare (only one IgG and five IgM cases).
Conclusions
Dr. Disanto and his team summarized four key insights:
B-cell recovery depends on age, sex, and total ocrelizumab exposure.
The more ocrelizumab someone has received, the slower memory B cells return.
Extended dosing may be biologically reasonable and appears clinically safe in stable patients.
IgG and IgM levels drop over time, but severe immune suppression remains uncommon.
These findings support the idea that personalized dosing, guided by blood monitoring of B cells, and regular monitoring of IgG and IgM, could maintain treatment effectiveness while minimizing side effects or infection risk.
Outlook: what comes next
Dr. Disanto highlighted the need for:
⭐ Randomized studies comparing standard vs. extended dosing.
⭐ Testing biomarkers (like NfL or GFAP) to detect subtle MS activity between infusions.
⭐ Deeper immune profiling to understand how B cells recover and maintain immune balance.
Takeaway for people with MS
For many, ocrelizumab remains one of the most effective therapies available. This study adds confidence that even when dosing intervals are safely extended, disease control can be maintained — and it provides clues for more individualized treatment in the future.
Cancer Risk Signals and MS Therapies: What We Can Learn from Real-World Safety Data
Presenter: Dr. Helly Hammer, University Hospital of Bern, Switzerland
Background
Multiple sclerosis (MS) is a chronic autoimmune disease that affects women about three times more often than men, typically starting between ages 20 and 40 — years that overlap with the highest reproductive activity. Because MS requires lifelong treatment, women with MS are exposed to disease-modifying therapies (DMTs) for many years, and questions about long-term cancer risks occasionally arise.
One important area of concern is HPV-related cancers (caused by human papillomavirus), such as cervical, vaginal, or uterine cancer. Women with MS may have fewer opportunities for HPV vaccination or regular screening, which could increase risk.
At the same time, vaccine hesitancy — often fueled by misinformation — has risen in parts of Europe and the U.S., even though extensive studies confirm that vaccines are safe and effective. For women with MS, vaccination against HPV can play a crucial preventive role.
What this study analyzed
Dr. Hammer’s team used real-world safety data from the FDA Adverse Event Reporting System (FAERS), covering the years 2012–2024.
They focused on female patients with MS and analyzed reports of tumors in reproductive organs and HPV-associated cancers.
Included data:
152,618 MS-related reports in total.
1,909 cases mentioning any form of cancer.
Only monotherapies were included (patients on one DMT).
Analysis compared five oral MS therapies:
Fingolimod
Dimethyl fumarate
Diroximel fumarate
Ozanimod
Teriflunomide
The team calculated reporting odds ratios (rOR) — a statistical measure to identify whether certain drugs appear more often in cancer reports than others.
Results
The analysis found elevated cancer signals in female MS patients treated with Fingolimod, compared to the other therapies.
Breast cancer: Slightly more often reported with Fingolimod, but not statistically significant.
HPV-related tumors: Higher with Fingolimod than with Dimethyl fumarate.
Uterine and vaginal cancers: Significantly higher reporting odds for Fingolimod than for Teriflunomide or Dimethyl fumarate.
Other DMTs (Dimethyl fumarate, Diroximel fumarate, Ozanimod, Teriflunomide) showed no clear increase in tumor reports.
Conclusions
Dr. Hammer emphasized that these are signal findings, not proof of cause. They highlight where further research is needed, not that one therapy directly causes cancer.
Key takeaways:
Fingolimod showed higher reporting rates for certain female cancers in the FAERS database.
Vaccination, especially against HPV, remains a key preventive measure to reduce cancer risk.
Ongoing monitoring and prevention strategies — including booster vaccinations and screening — are important for women receiving long-term MS treatment.
“Pharmacovigilance data give us early warning signs,” Dr. Hammer said. “They help us improve safety and prevention for women with MS who often live decades with their treatment.”
What this means for people with MS
For women living with MS, this research is not a cause for alarm, but rather a reminder to stay proactive:
Keep up with regular gynecological screening.
Ask your doctor about HPV vaccination, even if you are already on MS therapy.
Discuss any long-term safety concerns openly with your neurologist — data like these help the MS community build safer treatment plans together.
How MS Treatments Have Changed in France: The TEMPOS Study
Presenter: Dr. Julien Lannoy, France
Why this study matters
Over the past decade, the treatment landscape for multiple sclerosis (MS) has evolved dramatically. With the arrival of highly effective anti-CD20 therapies such as ocrelizumab and ofatumumab, neurologists now have new options for controlling disease activity early and more effectively.
However, despite these advances, treatment strategies differ widely from one region or specialist to another. The TEMPOS study was designed to look at how MS care has changed in real-world practice across France — who receives which treatment, how early, and for how long.
Study design
TEMPOS analyzed data from France’s national health database (SNDS), which covers nearly the entire population. Researchers identified 30,444 adults newly diagnosed with MS between 2016 and 2023.
Among them, 25,763 people started a disease-modifying therapy (DMT). The study looked at:
Which therapies were chosen first,
How treatment choices changed over time, and
How long patients stayed on their first treatment (“persistence”).
The average patient was 33 years old, and 70% were women — reflecting the typical gender ratio seen in MS.
Key findings
1️⃣ Major shift toward high-efficacy treatments
Between 2016 and 2023, there was a clear decline in the use of older, moderate-efficacy therapies (such as interferons or glatiramer acetate).
In 2016–2018, 65% of patients started on moderate therapies.
By 2022–2023, that number had dropped to around 22%.
At the same time, the use of anti-CD20 therapies increased sharply, showing a major shift toward earlier use of high-efficacy treatments.
2️⃣ Within anti-CD20 therapies, ofatumumab is on the rise
When anti-CD20 drugs were used as the first MS treatment, the proportion of patients starting on ofatumumab increased steadily, while ocrelizumab use decreased.
2016–2018: Ocrelizumab dominated (≈88%), Ofatumumab ≈12%.
2022–2023: Ofatumumab surpassed ocrelizumab (≈53% vs. 47%).
This likely reflects ofatumumab’s convenient self-injection format and increasing physician confidence in its safety profile.
3️⃣ Persistence: staying on treatment
After two years of follow-up:
81% of patients remained on anti-CD20 therapy,
75% on moderate-efficacy drugs,
61% on S1P therapies, and
54% on adhesion-molecule inhibitors (like natalizumab).
In other words, people were most likely to continue treatment long-term when they started with anti-CD20 therapies.
Study limitations
Dr. Lannoy noted a few important limitations:
Because the data came from insurance claims, the exact date of diagnosis can’t always be confirmed precisely.
For treatments taken at home, data reflect drug deliveries, not guaranteed consumption.
Rituximab (another anti-CD20 therapy sometimes used off-label) was not included but will be added in the next data update.
Conclusions
The TEMPOS study paints a clear picture of change in French MS care:
The arrival of anti-CD20 therapies has transformed treatment patterns.
There is a strong trend away from older, moderate therapies toward high-efficacy, MS-labeled anti-CD20 options.
Ofatumumab is steadily replacing ocrelizumab in new treatment starts.
These results underline how real-world practice is catching up with clinical evidence — early, effective treatment is becoming the new standard of care.
What this means for people with MS
For newly diagnosed people, this trend offers hope. It means that neurologists are increasingly confident in starting with powerful, targeted treatments right from the beginning — not waiting for disease activity to build up.
The data also show that most people stay on anti-CD20 therapy long-term, suggesting both effectiveness and tolerability in real-world settings.
As Dr. Lannoy summarized:
“In just seven years, the landscape of MS treatment has changed profoundly — and it’s continuing to evolve toward earlier, stronger, and more personalized approaches.”
When to Stop MS Treatment? A New AI Tool Helps Personalize That Decision
Presenter: Dr. Marisa McGinley, United States
Why this research matters
For people living with multiple sclerosis (MS), modern treatments can be very effective at reducing relapses and inflammation. But as patients get older and their disease becomes quieter, the question often arises:
👉 “Do I still need to stay on my medication — or could I safely stop?”
It’s a difficult decision. Stopping therapy could reduce side effects, infection risks, and costs — but it might also allow the disease to become active again. Until now, there have been no clear guidelines to help doctors and patients decide who can safely discontinue treatment.
The problem
Current evidence about stopping DMTs is mixed:
Observational studies (real-world data) suggest that older patients with stable disease can sometimes stop without problems.
Randomized controlled trials show more caution:
The DISCO-MS and DOT-MS studies both reported some recurrence of MS activity (on MRI or as relapses) after stopping therapy — particularly in younger patients or those who had recent inflammation.
So far, medical guidelines differ by country:
The U.S. and European recommendations generally advise continuing DMTs if a patient is still stable.
The UK and Canadian groups allow case-by-case discussion — but no universal stopping rule exists.
The goal of this new study
Dr. McGinley’s team aimed to create an individualized risk prediction tool — a digital model that can estimate a person’s personal risk of disease recurrence if they stop their DMT.
Using machine learning, the tool was trained to recognize patterns from thousands of patient records and to predict who is most likely to stay stable — and who might experience renewed MS activity.
Study design
The team analyzed data from two large groups:
1️⃣ Internal cohort – 3,526 MS patients followed in a large U.S. academic health system (2015–2023).
2️⃣ External validation cohort – data from the DISCO-MS clinical trial, involving 19 U.S. academic centers.
Patients had been on a DMT for at least one year and were monitored for new MRI lesions or relapses after discontinuation.
A random survival forest (RSF) model — a type of AI algorithm — was used to identify which factors best predict disease recurrence.
Key predictors of risk
The model identified 12 key factors that most strongly influenced outcomes, including:
Time since last MS activity (relapse or new MRI lesion)
Time since last MRI activity
Time on current therapy
Age
Disease duration
DMT type (CD20 therapy, fumarates, teriflunomide, etc.)
The model performed consistently well in both datasets, with an AUC of 0.65 — meaning it could correctly distinguish in about two out of three cases whether someone would remain stable or have new MS activity after stopping treatment.
Results
In the internal dataset, about 17% of patients who discontinued therapy had a return of MRI or relapse activity within 2 years.
In the DISCO-MS validation dataset, this was around 9% — showing similar patterns and good agreement between real-world and trial data.
Conclusions
Dr. McGinley’s group successfully developed and validated the first individualized AI-based tool to support decisions around stopping MS therapy.
Key takeaways:
The tool accurately predicts a person’s risk of disease reactivation after stopping treatment.
It was validated in both real-world and clinical trial populations.
It will soon be integrated into electronic health record systems and tested in clinical practice to support shared, personalized decision-making.
“This is about empowering patients and clinicians,” Dr. McGinley explained. “Instead of a one-size-fits-all rule, we can make data-driven, individualized choices about when — or whether — to stop therapy.”
What this means for people with MS
This research represents a step toward personalized MS care — where advanced data and AI tools can guide major treatment decisions.
In the future, people with stable MS might discuss stopping therapy with their doctor using their own individualized risk score, balancing safety, quality of life, and long-term health.
The tool will now be integrated into electronic health record systems and evaluated in clinical trials to confirm its safety and real-world usefulness.
Short wrap-up
Taken together, these studies reflect a clear trend: earlier, stronger, and more personalized MS care.
Anti-CD20 therapies continue to shape the modern treatment landscape — proving effective and well tolerated, but requiring vigilant monitoring for infections, antibody levels, and rare side effects like LON.
Real-world data (like TEMPOS) confirm that neurologists are increasingly confident to start highly effective therapies from the outset, while AI tools and biomarker monitoring are paving the way for smarter, individualized decisions — not only on when to start, but also when to safely pause or stop therapy.
In short: the MS field is moving toward precision medicine, where treatment is guided not by one-size-fits-all rules, but by your personal data, your safety, and your long-term well-being.
See you soon and try to make the best out of your life,
Nele
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