#098: New Research for Managing Primary Progressive Multiple Sclerosis (PPMS) an ECTRIMS Special

Primary Progressive Multiple Sclerosis (PPMS) presents unique challenges, as it often worsens without relapses and can significantly impact daily life. However, the growing body of research and treatment options is providing new hope for managing this condition. From exploring the effectiveness of established therapies like Ocrelizumab to cutting-edge advancements in CAR T-cell treatments, scientists and healthcare providers are uncovering ways to slow progression, improve outcomes, and enhance quality of life. This summary from ECTRIMS 2024 dives into the latest studies and innovations, offering insights to empower your MS journey.

Table of Contents

1. Anti-CD20 therapies in drug-naive primary progressive multiple sclerosis patients: A multicenter real-life study

by Dr. Marion Hay et. al (France)

Introduction

If you’re living with primary progressive multiple sclerosis (PPMS), you may have heard about anti-CD20 therapies. These treatments aim to slow disease progression by targeting specific immune cells. However, their effectiveness in PPMS is still debated. A recent multicenter study from France explored how these therapies compare to no treatment in drug-naive PPMS patients.

What Did the Study Explore?

The study followed 1,184 PPMS patients from the French MS Registry. Some had received anti-CD20 therapies, while others had not. Researchers looked at:

  • Time to Disability Progression: How long it took for symptoms to worsen.
  • MRI Activity: Brain imaging changes over two years.
  • Relapse Rates: Whether treated patients experienced fewer relapses.
  • Side Effects: The risk of serious infections.

Key Findings

  1. Disability Progression:

    • No significant difference was found between treated and untreated groups. This means the therapies did not slow physical disability progression in a measurable way.
  2. MRI Activity and Relapses:

    • MRI results and relapse rates showed no major differences between the two groups, though there was a slight, non-significant trend suggesting fewer relapses in the treated group.
  3. Infection Risks:

    • Treated patients had a higher rate of serious infections (6.67 infections per 100 person-years) compared to those untreated.
  4. Patient Characteristics:

    • Those who received treatment were generally younger, had shorter disease durations, and more active disease at baseline.

Why This Matters for You

This study shows that while anti-CD20 therapies may have a role in managing other forms of MS, their benefits in PPMS remain uncertain. With risks like serious infections, it’s essential to weigh the pros and cons with your healthcare provider.

How Reliable Is This Study?

This research is considered moderate-level evidence on the Cochrane scale because it used real-world data and robust statistical methods. However, as it was observational, it cannot definitively prove cause and effect. Larger randomized trials are needed for stronger conclusions.

What Can You Do?

  1. Stay Informed: Regularly discuss your treatment options with your doctor. New therapies and research are constantly emerging.
  2. Monitor Your Symptoms: Keep track of your progression and share changes with your healthcare team.
  3. Prioritize Well-Being: Focus on lifestyle choices like exercise, diet, and mental health, which are proven to improve quality of life in MS.

Takeaway

While anti-CD20 therapies may not significantly alter the course of PPMS, they are part of the growing arsenal of treatments being explored. This study reminds us of the importance of personalized care and ongoing research. Remember, you are not alone on this journey—advocate for your health and stay hopeful as science continues to advance.

2. Design of KYSA-7, A Phase 2, Open-Label, Randomized, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Treatment Refractory Primary and Secondary Progressive Multiple Sclerosis

by Prof. Dr. Ralf Gold et. al (Germany)

Living with primary progressive MS (PPMS) can feel daunting, as this form of MS comes with its unique challenges, including steady progression without relapses. However, groundbreaking research is offering hope, particularly through an innovative treatment known as CAR T-cell therapy. This is an exciting area of study, and here’s what the latest findings mean for you.


What Is CAR T-Cell Therapy?

CAR T-cell therapy is an advanced treatment originally developed for cancer. In MS, it is being adapted to target harmful B cells in the brain and spinal cord, which play a key role in the progression of the disease. This therapy works by genetically modifying a patient’s own immune cells (T cells) to target and destroy these problematic B cells.

The study focuses on KYV-101, a first-in-class, fully human CAR T-cell therapy. The goal is to see whether KYV-101 can slow down or halt disability progression in people with treatment-resistant PPMS or secondary progressive MS (SPMS).


What Did the Study Look At?

This research (called KYSA-7) is a Phase 2 trial that involves 120 participants aged 18-60 diagnosed with PPMS or SPMS. Participants had not responded adequately to previous treatments (like anti-CD20 monoclonal antibody therapies). The study is evaluating:

  • Primary goals: How effective KYV-101 is in slowing disability progression, measured over 12 weeks.
  • Secondary goals: Safety and any side effects, as well as changes in brain imaging and immune markers.

Key Findings So Far

Though this trial is ongoing, earlier research and related studies suggest:

  1. Targeted and Safe: CAR T cells expanded in the brain and spinal fluid, with no severe safety concerns noted.
  2. Promising Results in MS Biology: Patients who received the therapy showed a reduction in harmful immune activity, which could slow progression.

Why This Study Matters for You

For those living with PPMS, this trial represents hope for a new treatment option. Current therapies often focus on managing symptoms, but CAR T-cell therapy could directly impact the underlying disease process, potentially slowing or halting its progression.

This study is especially relevant for people with treatment-resistant forms of MS, offering a tailored approach to addressing progressive disability.


How Reliable Is This Research?

On the Cochrane evidence scale, this study is in Phase 2, meaning it’s designed to test both safety and efficacy in a moderately sized group. While not yet definitive, Phase 2 trials provide meaningful evidence of how well a treatment works and set the stage for larger trials. The use of rigorous scientific methods and an experienced international research team gives the findings significant weight.


What Can You Do?

  • Stay Informed: Follow updates on this and other CAR T-cell studies. Breakthroughs like this are worth watching closely.
  • Discuss with Your Doctor: Ask if you might qualify for similar trials or emerging therapies.
  • Focus on What You Can Control: While waiting for advances, maintain a healthy lifestyle and adhere to your current treatment plan.

Takeaway

CAR T-cell therapy like KYV-101 could mark a turning point for people with PPMS, targeting the disease at its root and offering new hope for slowing progression. While more research is needed, the journey toward innovative therapies like this is incredibly encouraging. Remember, you’re not alone in this—scientists and advocates are working tirelessly to improve care and outcomes for people like you. Stay positive, stay proactive, and take one step at a time!

3. Efficacy and security of ocrelizumab in patients with primary progressive multiple sclerosis (ppms) in a tertiary care hospital multiple sclerosis unit

by Alejandro Torres Moral et. al (Spain)

If you’re living with primary progressive multiple sclerosis (PPMS), you know how challenging it can be to manage this form of MS. A recent study looked into the safety and effectiveness of a treatment called Ocrelizumab (OCR) in a hospital setting. Here’s what it found and how it might relate to your journey with MS.


What Is Ocrelizumab (OCR)?

Ocrelizumab is a targeted therapy that works by depleting certain immune cells called B-cells, which are involved in the inflammatory and degenerative processes in MS. It was the first treatment approved for PPMS, offering hope for slowing down the disease’s progression.


What Did This Study Look At?

This study included 31 people with PPMS who were treated with Ocrelizumab. Researchers wanted to assess:

  • Effectiveness: How well the treatment worked in slowing disability progression.
  • Safety: Whether it caused any serious side effects.
  • Changes in Immune Function: How the therapy affected important immune markers like immunoglobulin levels (proteins that help protect against infections).

Key Findings

  1. Disability Progression:

    • Most patients (74.2%) experienced stable disability scores after two years, showing the therapy was effective for many in slowing progression.
  2. Immune Function:

    • Ocrelizumab lowered B-cell levels as intended, but also caused a decrease in immunoglobulin (IgG and IgM) levels over time.
    • Reduced immunoglobulin levels can slightly increase infection risk, and 9 patients in the study had infections, though these were largely manageable.
  3. Safety Profile:

    • Common side effects included urinary tract infections (UTIs) and mild skin issues.
    • Two patients experienced severe infections, one related to COVID-19 and another to an underlying immune issue.
  4. Previous Treatments:

    • Many patients in this study had tried other disease-modifying therapies before starting Ocrelizumab, highlighting its role as a treatment for those with few other options.

Why Does This Matter for You?

This study reinforces that Ocrelizumab can slow disability progression for many people with PPMS. While it’s not a cure, it offers a chance to manage the disease and preserve independence for longer. However, like any therapy, it comes with risks, including potential infections. That’s why careful monitoring by your healthcare team is essential.


How Reliable Is This Study?

This is a real-world observational study, meaning it looks at how the treatment works in everyday settings rather than in controlled clinical trials. On the Cochrane evidence scale, this provides moderate evidence—valuable insights but not as definitive as a randomized trial. Still, the findings align with broader research on Ocrelizumab, making them a meaningful addition to what we know about this therapy.


What Can You Do?

  • Talk to Your Doctor: If you’re not on Ocrelizumab but think it could help, bring it up during your next appointment.
  • Monitor Your Health: If you’re already taking Ocrelizumab, work closely with your healthcare team to keep an eye on immune markers and any signs of infection.
  • Stay Proactive: Keep up with recommended vaccinations and good hygiene practices to reduce infection risk.

Takeaway

Ocrelizumab represents a hopeful option for people with PPMS, helping to slow down the disease’s progression and offering a chance for better long-term outcomes. While it requires careful monitoring, its potential benefits make it a treatment worth considering if you’re navigating the challenges of PPMS. Remember, you’re not alone—advances in MS care are happening every day, and there’s support to help you on your journey.

4. GA Depot (long-acting IM injection of glatiramer acetate) Impact on EDSS stability in Relapsing forms of Multiple Sclerosis (RMS) and Primary Progressive Multiple Sclerosis (PPMS)

by Dr. Aaron Miller et. al (United States)

If you’re living with primary progressive multiple sclerosis (PPMS), finding treatments that help slow disability progression is likely a top priority. A recent study explored how Glatiramer Acetate (GA) Depot, a long-acting MS therapy, could play a role in stabilizing disability. Here’s a breakdown of the research and what it means for you.


What Is GA Depot?

Glatiramer Acetate (GA) Depot is a treatment administered every 28 days to help manage MS. It works by modifying your immune system to reduce inflammation and potentially slow disease progression. Unlike daily or weekly treatments, the long-acting nature of GA Depot offers added convenience.


What Was This Study About?

Researchers analyzed disability progression using a measure called the Expanded Disability Status Scale (EDSS). They collected data from three clinical trials that included both PPMS and relapsing-remitting MS (RRMS) patients. The goal was to see if GA Depot could help stabilize or slow the accumulation of disability over time.


Key Findings

  1. Stability Over Time:

    • In PPMS patients, the mean EDSS score remained stable over nearly three years (148 weeks). This means that disability levels didn’t significantly worsen during this time.
  2. Consistent Results in RRMS:

    • For RRMS patients, the EDSS scores remained stable over five years in an open-label study. This shows promise for GA Depot’s potential to help both progressive and relapsing forms of MS.
  3. Better Outcomes in Placebo-Controlled Trials:

    • In a one-year study, patients on GA Depot had less disability progression compared to those on placebo. The difference was statistically significant, meaning it’s unlikely to be due to chance.
  4. High Rates of Stabilization:

    • Across the studies, around 95% of patients on GA Depot showed stable or improved EDSS scores, suggesting the therapy could help preserve function over the long term.

Why Does This Matter for You?

This research highlights GA Depot as a potential option for stabilizing disability in PPMS. While it doesn’t reverse symptoms, it offers hope for slowing the progression of the disease and maintaining quality of life. The long-acting nature of the therapy also means fewer injections, which could simplify your treatment routine.


How Reliable Is This Study?

The study draws on data from multiple clinical trials, including placebo-controlled and long-term open-label designs. On the Cochrane evidence scale, this provides moderate to high reliability because of the consistent findings across different studies. However, as with any treatment, individual results may vary, and more research could strengthen the evidence further.


What Can You Do?

  1. Discuss with Your Doctor:

    • If you’re interested in GA Depot, ask your neurologist if it could be a good fit for your treatment plan.
  2. Track Your Progress:

    • Regularly monitor your EDSS score and any changes in symptoms to assess how your treatment is working.
  3. Stay Proactive:

    • Combine medical therapy with healthy lifestyle choices, such as staying active, eating well, and managing stress.

Takeaway

GA Depot offers a promising option for people with PPMS, showing potential to stabilize disability over the long term. While it’s not a cure, this therapy could help you maintain your independence and well-being. Remember, every step toward managing MS—whether through treatment, self-care, or support—adds up. If you’re considering new treatment options, why not explore this with your healthcare team? It could be a step toward a brighter, more stable future.

5. Impact of age on safety and effectiveness outcomes in persons with relapsing and primary progressive multiple sclerosis treated with ocrelizumab in the German real-world CONFIDENCE study

by Prof. Sven Meuth et. al (Germany)

Introduction:

If you’re living with primary progressive multiple sclerosis (PPMS), you’re probably familiar with the challenges of managing symptoms and maintaining your quality of life. This study explored the real-world safety and effectiveness of ocrelizumab (OCR), a treatment designed to target specific B-cells in the immune system, helping to reduce disease progression. Over five years, researchers looked at how well OCR worked and its safety in people with PPMS and relapsing MS (RMS).


What Was the Study About?

The research followed more than 3,000 people—505 with PPMS and the rest with RMS. Participants were monitored for up to 5 years after starting OCR treatment. The focus was on:

  • Safety: Tracking adverse effects like infections or other serious health issues.
  • Effectiveness: Measuring how OCR affected disability progression (using EDSS scores) and annual relapse rates (ARR).
  • Long-Term Impact: Investigating whether the treatment benefits persisted over time.

Key Findings:

  1. Safety:

    • No increase in adverse events (AEs) or serious adverse events (SAEs) was observed, even with longer treatment durations.
    • Common side effects included mild infections, but these were consistent with what is already known about OCR and other MS treatments.
  2. Effectiveness:

    • In people with PPMS aged 41–55 years, OCR helped stabilize their disability progression over the study period.
    • EDSS (Expanded Disability Status Scale) scores stayed stable over time, especially in younger participants with PPMS.
    • Relapse rates (ARR) were very low in all groups.
  3. Impact by Age:

    • Outcomes were better in younger PPMS participants (41–55 years) than in those over 55, suggesting that starting treatment earlier may be more beneficial.

Why Is This Study Important for You?

This research offers hope, showing that OCR is both safe and effective for managing PPMS in the real world. While it’s not a cure, OCR appears to slow down the progression of disability, especially if started early. Importantly, the treatment did not result in increased safety risks over time, which can provide reassurance for long-term use.


How Reliable Is This Study?

This was a real-world study, meaning it looked at how OCR works outside of a controlled clinical trial setting. While this type of study provides valuable insights into how treatments perform in everyday life, it’s considered moderate-level evidence on the Cochrane scale. It helps confirm the safety and effectiveness of OCR but isn’t as definitive as a randomized controlled trial (RCT).


What Can You Do with This Information?

  1. Talk to Your Healthcare Provider:

    • Discuss whether OCR might be a suitable option for you, especially if you’re in the early stages of PPMS.
  2. Stay Informed:

    • Keep an eye on new research to ensure you’re aware of the latest treatment options and recommendations.
  3. Prioritize Early Intervention:

    • If you’re newly diagnosed, starting treatment earlier could have a more significant impact on slowing disease progression.

Takeaway:

Ocrelizumab offers a promising option for managing PPMS, particularly for younger patients. By stabilizing disability and maintaining safety over the long term, it can help you take more control of your MS journey. While every person’s experience is unique, treatments like OCR provide an empowering reminder that there are tools available to help you live your best life with MS. Always work closely with your healthcare team to tailor your treatment plan to your needs.

6. Brain Volume Maps Identify Primary Progressive Multiple Sclerosis Patients at High Risk of Accelerated Atrophy

by Yehuda Warszawer et. al (Israel)

When living with Primary Progressive Multiple Sclerosis (PPMS), understanding how your brain changes over time can be a key part of managing your health. This study sheds light on how brain volume loss occurs in PPMS patients compared to healthy individuals, helping identify potential ways to support better outcomes.

What Did the Study Look At?

This research analyzed brain MRI scans from 169 PPMS patients and 169 healthy individuals, covering people aged 20–86. It aimed to map changes in brain volume in areas like the cortex, white matter, deep gray matter, thalamus, and cerebellum. The goal was to see how these changes relate to factors like disease duration and disability levels.

Key Findings

  1. Lower Brain Volume in PPMS:

    • PPMS patients had significantly lower brain volumes compared to healthy individuals, particularly in the cortex and thalamus.
    • For example, the odds ratio (OR) of having a low brain volume (<95% of the predicted normal range) was 23.34 for the brain parenchyma and 22.34 for the thalamus. This means these areas are much more affected in PPMS.
  2. Linked to Disease Duration and Disability:

    • Brain volume was lower in patients who had been living with PPMS longer.
    • Higher disability levels (measured by EDSS) were also associated with more pronounced brain volume loss.
  3. Gender and Age Considered:

    • The study adjusted for gender and age differences, ensuring the findings reflect true PPMS-related changes.

Why Does This Matter?

Brain volume loss is a marker of disease progression in PPMS. Identifying patients at higher risk allows healthcare providers to tailor treatment and potentially improve outcomes. While no treatment can fully reverse these changes, early intervention could help manage their impact.

How Reliable Is This Study?

This study used high-quality MRI technology and a robust comparison between patients and healthy individuals. It provides moderate-level evidence on the Cochrane scale. However, it’s observational, meaning it shows correlations rather than proving cause-and-effect relationships.

What Can You Do?

  • Talk to Your Doctor: Discuss how brain health monitoring can be part of your treatment plan.
  • Focus on Brain Health: Stay active, eat well, and engage in mental exercises, which might support overall brain function.
  • Stay Informed: As research evolves, new strategies may emerge to address brain changes in PPMS.

Takeaway

While brain volume changes in PPMS can feel like a challenging aspect of the disease, understanding them helps you take proactive steps. Remember, knowledge is power. By working closely with your healthcare team, you can tailor your care to support the best possible outcomes.

Living with PPMS can feel overwhelming at times, but you are not alone. Research is advancing rapidly, with treatments and approaches designed to help slow progression, maintain independence, and enhance quality of life. Whether it’s monitoring your brain health, considering therapies like Ocrelizumab or GA Depot, or staying informed about revolutionary trials like CAR T-cell therapy, there is a growing arsenal of options to explore.

Remember, your journey with MS is unique, and the best path forward is one tailored to your needs in collaboration with your healthcare team. Stay proactive, prioritize your well-being, and take comfort in knowing that science, advocacy, and community support are on your side. Every small step—whether it’s discussing a new treatment or making a lifestyle change—can bring you closer to a brighter future. Keep believing in your strength and the progress that’s being made for us and our community.

See you soon and try to make the best out of your life,
Nele

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Nele von Horsten

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I show you how to make the best of your life with MS from family to career to hobbies. Thanks to science and research, a lot is possible nowadays.

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