A new year promises to bring a wealth of new insights into the nature and management of multiple sclerosis (MS). The study summaries included in this edition of “What’s New in MS Research” highlight the broad spectrum of inquiry that is driving the progress to develop better treatments against the disease.
The clinical trials and other analyses to follow examine topics ranging from the impact of discontinuing or switching disease-modifying therapies (DMTs), to associations between MS and weight gain, as well as MS and COVID-19 infection. The studies also highlight recent evidence of the effectiveness of various DMTs and the connection between overall health and MS outcomes.
The bottom line: There is abundant cause for hope and considerable opportunity to take a proactive approach to optimizing your physical and emotional well-being.
Does it make sense to stop disease-modifying therapy (DMT) following a long period of stability on treatment? It’s a question that many people with MS ask themselves after 10, 20, or even more years of taking medication.
While discontinuing therapy can be an attractive option in terms of cost savings and avoiding potential side effects of treatment, a study from the Netherlands shows that those benefits can come at the price of increased risk of renewed MS activity.1
The study involved 89 adults with relapsing-onset MS who had not experienced relapses or substantial magnetic resonance imaging (MRI) evidence of disease activity over the course of five years on their initial DMT. Study participants had a median age of 54 years, and two-thirds were female. The people in the study were assigned in random fashion to either continue or discontinue their therapy.
After a median follow-up of 15.3 months, the trial was stopped ahead of schedule because of inflammatory disease activity beyond pre-defined acceptable limits. Specifically, eight of the 45 people in the discontinuation group had recurrent inflammation. In most cases, that inflammation involved new or newly active brain lesions identified on MRI. However, two of the people had clinical relapses. By contrast, none of the 44 people assigned to continue their DMT had significant inflammatory disease activity.
Among the eight people who had imaging evidence of inflammation or a clinical relapse, the median time from DMT discontinuation to recurrent disease activity was 12 months.
The study’s authors note that in their trial, “Even in patients with long-term MS [whose disease activity was] stable for over five years, first-line DMT discontinuation can lead to recurrence of inflammatory disease activity. Although this study cohort was relatively small, the recurrence of inflammation in the discontinue group was significantly higher than in the continue group.”
Decisions about whether to maintain or stop DMT regimens involve consideration of several factors, including many that are specific to each person. Those decisions are best made in consultation with one’s MS clinician and in view of the latest available evidence. This study’s finding that roughly one in six people who discontinued their DMT experienced recurrent disease activity within a median one year of stopping therapy provides important data to discuss in the process of shared decision-making, which refers to the process of patients working together with their healthcare team to determine their best treatment plan.
In December 2024, the Food and Drug Administration (FDA) granted Breakthrough Therapy designation to tolebrutinib, an investigational, oral medication being developed by the French biopharmaceutical company Sanofi for the treatment of non-relapsing secondary-progressive multiple sclerosis (nrSPMS).2 The FDA designation is designed to expedite the development and review of medicines that target serious or life-threatening conditions. Medications qualifying for this designation must show the potential for substantial improvement in clinically significant endpoints versus currently available therapies.
While more than 20 disease-modifying therapies (DMTs) are approved for use in various forms of relapsing MS, none are specifically approved for nrSPMS, a condition in which people initially diagnosed with relapsing-remitting MS experience progressive disability without having relapses.
Sanofi said that the Breakthrough Therapy designation was based on positive results from the Phase III HERCULES study involving more than 1,100 people with nrSPMS. The study found that tolebrutinib delayed the time to onset of six-month confirmed disability progression (CDP) by 31% compared to placebo. Further, 10% of study participants receiving tolebrutinib experienced confirmed disability improvement, compared to 5% receiving placebo.
The study also found a higher incidence of liver enzyme elevations in the tolebrutinib group than the placebo group. Just over 4% of people receiving tolebrutinib had liver enzyme levels more than three-times the upper limit of normal (ULN), compared to 1.6% of people in the placebo group. Sanofi noted that 0.5% of people in the tolebrutinib group experienced peak increases in a specific liver enzyme (alanine aminotransferase [ALT]) that were more than 20 times the ULN, all within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention, the Company said.
Tolebrutinib belongs to a class of medications known as Bruton’s tyrosine kinase (BTK) inhibitors. BTK is an enzyme that helps govern the activity of different cells involved in neurological and immune functions. The enzyme has been shown to play a role in the development and activation of B cells, which are immune cells that contribute to the development of MS.
Tolebrutinib is able to penetrate the brain to better reach areas of inflammation, while reaching levels of concentrations within the cerebrospinal fluid to enable it to modulate B cells and microglia. Both of these support the immune system, and the microglia are also involved with brain development, maintenance of neuronal networks, and repair of injured nerves. In addition to the HERCULES trial evaluating tolebrutinib in nrSPMS, the Phase III PERSEUS study is assessing the medication in primary-progressive MS. Results from that study are expected in the first half of this year.
On January 22, the Food and Drug Administration (FDA) issued a warning about the risk of anaphylaxis, a rare but serious allergic reaction, with use of the disease-modifying therapy (DMT) glatiramer acetate, which is marketed as Copaxone® and Glatopa®.3
In announcing the warning, the FDA wrote that the reaction “can occur at any time while on treatment, after the first dose or after doses administered months or years after starting the medicine. For most patients who experienced anaphylaxis with glatiramer acetate use, the symptoms appeared within one hour of injection. In some cases, anaphylaxis resulted in hospitalization and death.”
The federal agency said that it was adding the risk of anaphylaxis to a new Boxed Warning, its most prominent type of warning, and to the Warnings and Precautions section of the prescribing information for glatiramer acetate.
The FDA explained, “We identified 82 worldwide cases of anaphylaxis associated with glatiramer acetate occurring from December 1996 through May 2024, including 19 cases that reported anaphylaxis more than one year after starting the medicine.” The agency’s announcement continued, “The 82 worldwide cases include only reports submitted to FDA and found in the medical literature, so there are likely additional cases about which we are unaware. While anaphylaxis in these cases appears to be rare compared to how often the medicine is used, these 82 patients reported serious outcomes that required emergency room visits or hospitalizations for medical treatment, and six died.”
Copaxone was one of the first DMTs to receive FDA approval, which was granted in 1996. Since then, it has been used by hundreds of thousands of people with relapsing forms of MS. Glatopa is a generic version of glatiramer acetate that has been available since 2015. It, too, has been used by numerous people with multiple sclerosis since its approval for treatment of relapsing MS. The FDA reported that in 2023 alone, an estimated 240,000 glatiramer acetate prescriptions were dispensed.
The FDA noted that symptoms of anaphylaxis include wheezing, difficulty breathing, swelling of the face, lips, or throat, and hives. “These symptoms can quickly progress to more serious symptoms, including severe rash or shock, which is a life-threatening condition,” the agency said. It added, “Patients should be aware that the early symptoms of anaphylaxis can be similar to a temporary reaction that sometimes happens right after or within minutes after an injection of the medicine into the skin. This immediate post-injection reaction goes away on its own, usually within 15-30 minutes, with no specific treatment. This reaction can occur with the first dose, or after doses administered months or even years after starting the medicine. This immediate post-injection reaction may involve symptoms such as flushing, chest pain, palpitations, anxiety, shortness of breath, rash, or hives. Call the health care professional who prescribed the medicine if you have any of these immediate post-injection reaction symptoms. Do not continue taking more injections until your prescriber tells you to do so. Seek immediate medical attention by going to an emergency room or calling 911 if any of these symptoms worsen or do not go away.”
The agency added, “We cannot determine how likely it is that someone will experience these side effects when taking glatiramer acetate. Your healthcare professionals know you best, so talk to them if you have questions or concerns about risks of taking glatiramer acetate.”
In addition to being aware of the symptoms of anaphylaxis described above, the FDA’s advice to talk with your MS clinician is particularly important guidance for people taking Copaxone or Glatopa. Together, you can assess the benefits and risks of your current therapy and potential alternatives, ensure that you have a plan of action should you experience concerning symptoms, and decide on the approach that’s best for you.
Urinary tract infections (UTIs) are responsible for more hospital admissions among people with multiple sclerosis (MS) than any other cause, according to a recently published study.4
Researchers examined the records of 210 adults with MS who were admitted to Duke University Hospital between January 2018 and January 2020. They found that 10.3% of the admissions were for UTIs. The next most-frequent causes were neurologic deficits of nonidentifiable cause (9.2%), MS exacerbation (7.6%), and falls/ambulation difficulty/spasticity (6.2%).
Having MS did not appear to contribute to a significantly longer hospital stay or a greater risk of being re-admitted to the hospital within 30 days of discharge. The average length of stay was 6.1 days for people with MS versus 5.5 days for the general population, while 30-day re-admission rates were 14.9% and 15.5%, respectively. Interestingly, almost half of the people with MS (48.5%) were not taking a disease-modifying therapy (DMT) upon admission.
The study’s authors concluded, “Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS.”
This study, while conducted at a single institution and involving a modest-sized population, is consistent with other research on the causes of hospitalization in people with MS. Its findings underscore the value of talking with your clinician about approaches to managing urinary incontinence, urinary retention, and similar conditions that are common in MS and that increase risk for UTIs.
While many UTIs do not cause symptoms, the study also highlights the importance of promptly contacting your primary care provider or MS clinician should you experience possible indicators of a UTI. These include pain or burning with urination, an urgent need to urinate frequently, or cloudy or bloody urine.
A study involving 218 adults with MS found that a reduction in symptoms of depression was accompanied by a reduction in the impact that fatigue had on people’s lives.5
Most study participants were female (72%), white (76%), and middle-aged (average age 53.7 years). Their average time since MS diagnosis was 12.5 years. They were assigned at random to a fatigue self-management intervention or to receive general MS education on improving fatigue. Researchers noted that the two interventions showed similar efficacy.
Rather than stopping there, however, the investigators went on to conduct a secondary analysis. They looked at whether a clinically significant improvement in depressive symptoms over the course of the trial (as measured by at least a 17.5% reduction in total Beck Depression Inventory-II score), correlated with a reduction in measures of the impact of fatigue, from the start of the study through a six-month follow-up.
The researchers found that improvement in their Be
