What’s New in MS Research – November 2022

Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD

Experts in every aspect of multiple sclerosis (MS) gathered in Amsterdam, The Netherlands, in late October 2022 to unveil research results and share ideas at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

With more than 1,200 bridges, the Dutch capital was an appropriate location for a meeting dedicated to connecting the findings from laboratory research and clinical trials to enhancements in patient care. In much the same way, “What’s New in MS Research” is provided to connect people with MS to information that can help them optimize their health and engage in shared decision-making with their clinicians.

The wide range of research advances unveiled at the ECTRIMS meeting is reflected in the items that follow. Those items cover topics including:

  • Gynecologic and obstetric implications of taking disease-modifying therapies (DMTs)
  • The long-term impact of MS and its treatment on disease status and employment
  • How the effectiveness of stem cell transplantation compares with that of various DMTs
  • Promising new therapies being evaluated in clinical trials
  • Efforts to identify and address deficits in clinicians’ knowledge of the impact of race and ethnicity in MS (through an initiative co-sponsored by the Multiple Sclerosis Association of America)
  • The ability of online interventions to help people with MS improve symptoms of depression and urinary incontinence

Why regular cervical screenings are critical for women on high efficacy DMTs

A recent study found that women with MS taking a high efficacy disease-modifying therapy (DMT) had a rate of abnormal cervical screening tests more than three-times higher than that of women taking a low efficacy DMT. 1

The multi-center study evaluated 248 women who had at least one cervical screening test – such as a Pap smear or liquid-based cervical cytology test – after the onset of MS and no prior history of an abnormal screening result.

The rate of new abnormal screening tests was 36.6% among women taking high efficacy DMTs, including Gilenya® (fingolimod), Mavenclad® (cladribine), Vumerity® (dimethyl fumarate), Tysabri® (natalizumab), Ocrevus® (ocrelizumab), Rituxan® (rituximab), and alemtuzumab. By contrast, the rate was 10.2% among women taking DMTs that investigators categorized as having relatively lower efficacy, including interferon beta, glatiramer acetate, and Aubagio® (teriflunomide). The difference between the two rates was statistically significant. Further, the difference persisted after investigators made adjustments for factors that can affect the risk for cervical abnormalities, including smoking, use of hormonal medications, and being vaccinated against human papillomavirus (HPV), a virus that contributes to precancerous changes in cervical tissues and the development of cervical cancer.

The study’s authors said, “This finding is vitally important for the safety of women with MS and will have direct clinical implications for primary and secondary prevention strategies, including cervical cancer screening frequency and human papillomavirus (HPV) vaccination.”

The findings, while unquestionably important, need to be evaluated in context. People with MS and their clinicians choose high efficacy DMTs specifically because of the impact those medications have in terms of reduced relapses, decreased disability, and other aspects of living with MS. Across all areas of medicine, medications that deliver more potent benefits often have more significant side effects, which is why careful consideration of the benefit:risk calculation of a treatment is a key component of shared decision-making. Cervical screening identifies a wide range of abnormalities, from highly treatable potentially precancerous changes in cells to cancer itself. However, it is quite uncommon for fully developed cancer to be found in a woman who previously had normal results on regular screenings. The bottom line: Talk with your MS clinician and your gynecologic care provider about any concerns, be sure the gynecologic provider knows what medications you are taking, and stay on schedule with your cervical screenings.

Comparing stem cell transplantation with three DMTs in relapsing-remitting MS

Stem cell therapy is an emerging treatment option for people with highly aggressive MS. But how does the effectiveness of this approach compare with that of potent DMTs such as Gilenya® (fingolimod), Ocrevus® (ocrelizumab), and Tysabri® (natalizumab)? A recent international study examined that question.2

Investigators in Canada, Sweden, the United Kingdom, and Australia identified 327 individuals with MS who had undergone autologous hematopoietic stem cell transplantation (AHSCT) at their centers. In AHSCT, physicians treat a patient so that his or her bone marrow releases stem cells that have the potential to become various types of blood cells, such as platelets, which play a role in controlling bleeding; red blood cells, which carry oxygen; and white blood cells, which fight infection and perform other important immune functions. Once those stem cells have been released into the circulation, physicians collect the cells from the bloodstream and store them while the patient receives chemotherapy to partially or completely suppress the immune system. The cells are then infused back into the patient through a vein, and these help to “reset” or “reboot” the immune system.

The researchers drew on data from the MSBase registry to match stem cell transplant patients with people with MS who had similar disease characteristics and who were receiving one of the three high efficacy DMTs being studied. The study examined data on 612 people receiving Gilenya, 606 receiving Tysabri, and 303 receiving Ocrevus.

The individuals studied had a high rate of disease activity and average Expanded Disability Status Scale (EDSS) scores of 3 to 4.

Key findings:

  • Compared to people receiving Gilenya, AHSCT patients had fewer relapses and a 2.6-times greater chance of disability improvement.
  • The risk of relapse and the annualized relapse rate (ARR) were similar among AHSCT patients and those receiving Ocrevus.
  • Risk of relapse and ARR also were similar between AHSCT patients and people receiving Tysabri, but improvement in EDSS score was 1.8-times more common after stem cell transplantation.

The researchers concluded, “Among patients with highly active MS with moderate disability, AHSCT is superior to fingolimod and comparable with ocrelizumab and natalizumab in preventing relapses. AHSCT is associated with higher rate of recovery from disability than natalizumab, a therapy that is known for reduction of disability in trials.”

Of course, effectiveness is only one side of the clinical coin when it comes to selecting therapies, as adverse effects also must be considered. Further, cost, accessibility, and other real-world issues also come into play. Nevertheless, the study makes a substantial contribution to the effort to help people with highly active relapsing MS and their clinicians understand the relative merits and drawbacks of various treatment options. 

Tracking long-term employment status after a first demyelinating event

Almost 90% of people who had a full-time job when they were diagnosed with a first demyelinating event were still working full-time a year later, but only 42% were working full-time 10 years after that initial event.

That was one of the main findings from an Australian study of 237 adults who were followed for 11 years after their first clinical diagnosis of central nervous system (CNS) demyelination.3

The study also found that people who progressed from that first event to clinically definite MS were 4.45-times more likely than those who did not progress to transition to a “deteriorated employment state,” meaning moving from full-time employment to part-time work or unemployment, or going from part-time work to being unemployed.

Women were at roughly 2.5-times greater risk than men of seeing their employment status reduce over time. Further, as might be expected, people with more relapses or a greater level of disability were at increased risk of a negative change in employment status compared with those with fewer relapses or relatively less disability. Meanwhile, people with a university education were six-times more likely than those with a high school education to be able to re-enter the work force following unemployment.

While the labor market and labor laws in Australia obviously differ from those in the United States, the concerns and questions prompted by a first demyelinating event are universal. This study underscores the need to focus on long-term occupational and financial-planning considerations – in addition to the paramount concern with health and wellbeing – following a first episode of demyelination.

How late-onset MS differs from multiple sclerosis diagnosed at an earlier age

A growing number of MS cases are being diagnosed in people age 50 years or older. In addition to investigating the reasons for this phenomenon, which is known as late-onset multiple sclerosis (LOMS), researchers are examining how MS that emerges later in life differs from MS diagnosed when people are ages 18 to 49.4

British investigators drew on data from the UK MS Register to identify differences between 1,608 people with LOMS and 15,516 people classified as having adult-onset MS (AOMS), meaning that they were diagnosed after 17 and before 50 years of age. Compared to people with AOMS, the investigators found:

  • A lower proportion of women in the LOMS group (62.8% vs. 75.4%)
  • A higher proportion of people with primary-progressive MS (39.7% vs. 9.4%)
  • A higher level of disability at diagnosis (median MS Impact Scale score of 36.7 vs. 28.3)

All of those differences were statistically significant.

The researchers also conducted a smaller study looking at pathological aspects of MS in 21 people with LOMS and 20 with AOMS. They found that demyelinated lesions were smaller and were seen less often in people with LOMS compared to those with adult-onset MS, and that neuron loss was somewhat independent of such lesions in LOMS. They concluded that those findings “suggest differing underlying biological processes that may benefit from more targeted treatment.”

By identifying key differences within the overall population of people with MS, studies such as these help researchers develop and clinicians deliver highly targeted therapies and individualized treatment plans..

Investigational medication shows reduction in MRI activity vs. placebo

Vidofludimus calcium, or VidoCa, is an investigational medication being evaluated in a Phase III trial of people with relapsing MS and in a Phase II study of people with progressive MS. The oral medication belongs to a class of agents called dihydroorotate-dehydrogenase (DHODH) inhibitors. These medications affect two types of white blood cells – T lymphocytes and B lymphocytes – which play an important role in the immune system. Through their impact on those cells, DHODH inhibitors reduce the inflammatory response seen in autoimmune conditions.

In the Phase II EMPhASIS trial, 268 people with relapsing-remitting MS received one of three daily doses of VidoCa – 10 mg, 30 mg, or 45 mg. Other study participants received placebo. All of the participants had magnetic resonance imaging (MRI) at baseline and every six weeks thereafter until Week 24, which was the end of the treatment period.5

Researchers reported that compared to the study participants receiving placebo, people receiving 30 mg of VidoCa had a 76% reduction in combined unique active lesions seen on MRI. The relative reduction was 71% in the people receiving 45 mg of VidoCa, while there was no difference in active lesions between the placebo group and the group receiving 10 mg of VidoCa. In terms of gadolinium-enhancing lesions, the relative reduction compared to placebo was 78% for the 30-mg group, 74% for the 45-mg group, and 13% for the 10-mg group. Meanwhile, from baseline to Week 24, Expanded Disability Status Scale (EDSS) scores worsened slightly in the placebo group, remained unchanged in people receiving 10 mg of VidoCA, and improved modestly in those receiving 30 mg or 45 mg of VidoCa.

Investigators said that the safety profile and tolerability of VidoCa in EMPhASIS were similar to the results of earlier trials, with no new safety signals emerging.

Those researchers concluded, “This analysis confirms the 30-mg and 45-mg doses as appropriate for Phase 3 evaluation in MS.”

Welcome news on fertility treatment and relapses, as well as maternal DMT use and infant health

Fertility treatment did not increase the risk of relapse in 55 women with MS or clinically isolated syndrome (CIS), according to a study conducted by researchers at several centers in the US.6

The women participating in the study had an average age of 36.5 years when they received fertility treatment and an average disease duration of 8.2 years. Forty-eight had MS, while seven had CIS. Between them, they received 110 cycles of fertility treatment. Fifty-six percent had in vitro fertilization, which entailed controlled ovarian stimulation followed by egg retrieval and embryo transfer; 17% had controlled ovarian stimulation followed by egg retrieval only; and 27% had embryo transfer only.

Five relapses occurred in the three-month period following fertility treatment, with four women having one relapse each and one woman having two relapses. None of those relapses occurred in women who were receiving disease-modifying therapy (DMT) at the time of their fertility treatment. For the fertility treatment cycles in which women were not taking a DMT, the relapse rate in the following three months was 0.30, compared to 0.26 in the period before fertility treatment, a difference that was not statistically significant.

For treatment cycles resulting in pregnancy, the women’s annualized relapse rate declined from 0.26 to 0.09, which was statistically significant.

The researchers concluded, “In this modern case series of 110 fertility cycles, we did not observe an elevated risk of relapses after FT [fertility treatment]. Continuing DMT during FT may reduce the risk of relapse during this period of marked hormonal fluctuations.”

Of course, the reproductive-related concerns of women with MS don’t end when pregnancy begins. There also are considerations regarding whether to continue disease-modifying therapy during pregnancy and while breastfeeding, both in terms of the woman’s risk of relapse and of any potential impact on the child’s health. A recent study from Germany provided reassuring findings on this last topic.

Drawing on data from the German MS pregnancy registry, researchers evaluated B-cell counts and other clinical data for 44 infants whose mothers had taken anti-CD20 disease-modifying therapies before or during pregnancy and/or while breastfeeding. These therapies, which included Ocrevus® (ocrelizumab) and Kesimpta® (ofatumumab), reduce B-cell counts in patients, prompting investigators to examine any possible pass-through effects in the women’s children. Lowering the number of infection-fighting B cells in people with MS reduces the inflammation that is a hallmark of autoimmune conditions, but it can also increase susceptibility to infection, which obviously would be problematic for infants.7

Forty-one of the infants’ mothers had taken anti-CD therapies before or during pregnancy, with 35 taking Ocrevus and six taking Rituxan® (rituximab), which is approved in the United States to treat many cancers, autoimmune conditions, and other diseases, but not for MS. Of those women, three also took Ocrevus while breastfeeding and one took Rituxan while breastfeeding. Meanwhile, three infants’ mothers took either Ocrevus or Kesimpta during breastfeeding, but not during pregnancy.

The investigators looked at infant B-cell counts that were measured an average 19.4 days after birth and found that those values were, on average, in the standard range for the first month of life. There were two cases in which complete B-cell depletion after exposure to Ocrevus in the second and third trimesters of pregnancy was followed by complete B-cell repopulation at two months. None of the children studied had congenital malformations or severe infections within the first year of life.

The investigators concluded, “If administered before or at the beginning [of] pregnancy and/or lactation, anti-CD20 [therapies] seem to be safe without a depleting effect on the physiological B-cell development in exposed infants. Active attempts of conception can be planned shortly after the infusion/injection. Exposure in the second or third trimester can lead to B-cell depletion as the [medication] can cross the placenta [so this] should be monitored and live vaccines postponed.

Examining how initial experience with DMTs correlates with longer-term outcomes

People with relapsing-remitting MS who have disability progression or worsened cognitive function during their first two years on disease-modifying therapy (DMT) are likely to have further declines in physical and psychological health at five years, according to a recent analysis.8

Researchers drew on the Swedish MS registry to evaluate the relationship between response to DMTs at the two-year mark and people’s subsequent course. They evaluated data on more than 1,900 people aged 18 to 55 years of age at baseline who had an Expanded Disability Status Scale (EDSS) score of 5.5 or less. (The scale runs from 0 to 10, with 0 representing a normal neurologic examination and no disability in any functional system, and 10 signifying death due to complications of MS. A score of 5.5 represents disability severe enough to preclude full, daily activities.)

Investigators looked at changes from initiation of therapy to two years of use as measured by: the EDSS; the annualized relapse rate (ARR); and the Symbol Digit Modalities Test (SDMT), which measures processing speed, an important component of cognitive function. They also used the MS Impact Scale-29 (MSIS-29) to evaluate the study subjects’ physical and psychological status.

The analysis showed that an increase in EDSS score from baseline to two years, which indicates disability progression, was related to worsening in physical MSIS-29 score at five years and 10 years, and to worsening in the psychological MSIS-29 score at five years. Similarly, a decrease in the SDMT score from baseline to 24 months, which signifies worsened cognitive function, was related to declines in both physical and psychological performance at five years, as measured by the MSIS-29 instrument. The relationships between early changes in EDSS and SDMT scores and later MSIS-29 scores were statistically significant. By contrast, changes in the annualized relapse rate did not show a significant relationship with later MSIS-29 scores.

The finding that people who had declines in their physical and cognitive status in their first two years on a DMT went on to experience further worsening may not be surprising. However, that information may help inform the current debate about whether people should begin treatment on a relatively less potent therapy with fewer side effects and then advance to a higher potency DMT with the potential for more side effects, or should instead take a higher potency DMT right from the start.

Further, the authors noted, “As relapses did not significantly contribute to patient-reported long-term impact of MS in this analysis, a focus on the prevention of additional mechanisms driving short-term disability progression and cognition could therefore potentially have a positive impact on long-term QoL [quality of life].

Identifying – and addressing – knowledge deficits on how race and ethnicity impact MS

While Black people have the highest mortality rate among individuals with MS younger than 55 years, barely half of neurologists and just over one-third of primary-care providers (PCPs) participating in an online medical education program were aware of that fact.9

That deficit in clinician knowledge regarding the impact of ethnicity and race on MS was one of several findings to emerge from the recent medical education activity, which was organized by the Multiple Sclerosis Association of America and Medscape, LLC. Faculty members for the activity were: Mitzi Joi Williams, MD; Lilyana Amezcua, MD, MS; John A. Lincoln, MD, PhD; and patient advocate Anita Williams. An analysis of participant answers on a pre-meeting questionnaire showed that neurologists were slightly more likely than PCPs to appreciate how ethnic background can affect people’s access to neurological care. Sixty-three percent of neurologists and 59% of PCPs correctly identified that Whites visit outpatient neurologists more often than Blacks or Hispanics. Based on answers to other questions, a higher proportion of neurologists than PCPs demonstrated cultural competence in a patient-care scenario and were confident in their ability to manage people with MS from all ethnic backgrounds.

While the effort to eliminate disparities in healthcare begins with identifying deficits in knowledge and other factors that contribute to inequities, progress requires moving from awareness to action. Clinicians participating in the medical education program reported that they were willing to take that next step. When asked how they planned to change their practice based on the activity:

  • 35% of neurologists and 34% of PCPs said they would modify their treatment plans
  • 24% of neurologists and 23% of PCPs said they would change their screening practices
  • 24% of neurologists and 19% of PCPs said they would use alternative communication methodologies
  • 24% of neurologists and 15% of PCPs said they would refer patients to an appropriate clinical trial

The neurologists said that lack of time, insurance/payer issues, and institutional limitations were the top barriers they faced in making such changes, while the PCPs cited patient adherence/compliance as the main obstacle they faced, followed by insurance/payer issues and institutional limitations. While such challenges are real and enduring, the knowledge deficits identified in this medical education activity help drive home the reality that disparities in care are also enduring and will be overcome only with a sustained effort.

Assessing fall risk in people with MS

As a phrase, “isokinetic dynamometry” may not come trippingly off the tongue, but as an assessment, it may play a key role in identifying which people with MS are at greatest risk for trips and falls.

An isokinetic dynamometer is a device found in many physical therapy and rehabilitation medicine facilities. It records the force a user applies throughout a range of motion, such as when someone who is seated lifts one leg off the floor and extends it out in front, going from a bent to a straightened knee.

Danish investigators recently employed the device to explore an association between neuromuscular function and risk of falling in 53 people with MS.10 The researchers had those people report how many times they had fallen in the past year. Based on those reports, 24 study participants were classified as non-fallers, eight were categorized as one-time fallers, and 21 were recurrent fallers.

When the researchers then looked at the results of lower-extremity neuromuscular function tests performed on an isokinetic dynamometer, they found that the people who had fallen once or repeatedly in the past year had impaired function compared to the people who had not fallen. Those results held up across age groups and regardless of the subjects’ sex.

It may seem obvious that worse lower-extremity neuromuscular function would be associated with a greater risk of falling. However, the real value of this study may not lie in providing confirmation of what common sense would suggest, but rather in validating a method that physical therapists, exercise physiologists, and other MS clinicians can use to determine an individual’s fall risk and to then counsel them accordingly.

Online interventions help reduce depression as well as urinary incontinence in MS

A host of emotional and physical conditions can accompany MS, with depression and urinary incontinence being among the most common. Two separate randomized controlled trials have demonstrated that online programs can help treat those conditions in people with MS, suggesting that the telehealth approach that came to the forefront during the first months of the COVID-19 pandemic may have enduring value in delivering care to the MS community.

In the first study, researchers in Germany, the United States, and Switzerland evaluated the ability of an MS-specific, internet-based, cognitive behavioral therapy (iCBT) program to reduce depressive symptoms. The Phase III study enrolled 279 people with neurologist-confirmed MS. Those people were randomized 1:1:1 to receive therapist-guided iCBT, stand-alone iCBT, or treatment as usual. The study’s primary endpoint was severity of depressive symptoms as assessed by the Beck Depression Inventory – II (BDI-II) 12 weeks after randomization.11

At Week 12, 18% of participants had dropped out of the study. Among those who remained, people participating in iCBT had a greater reduction in depressive symptoms than those who received treatment as usual. People in the stand-alone iCBT group had an average 6.3-point greater change in the BDI-II than those in the treatment-as-usual group, while people receiving therapist-guided iCBT group had an average 5.8-point greater change. Both differences were statistically significant.

There were no reports of suicidal ideation or intent during the trial. Three people in the treatment-as-usual group had clinically relevant worsening of depressive symptoms, as did one person in the stand-alone iCBT group. There were no reported cases of clinically relevant worsening of symptoms in the therapist-guided iCBT group.

In the second study, Turkish researchers randomized 45 people with MS and urgency urinary incontinence to either perform home-based pelvic floor muscle training on their own, participate in telerehabilitation-based pelvic floor muscle training, or be part of a non-intervention control group.12

After 12 weeks of follow-up, people in both the telerehabilitation program and home-based program had statistically significant reductions in number of urine leaks, use of pads, and urinary incontinence severity, as well as improvement in quality of life. As might be expected, there were no significant changes in these measures in the control group. Interestingly, while both groups performing pelvic floor muscle exercises had reduced symptoms and better quality of life, patient satisfaction and compliance with the exercise program were greater in the people participating in the telerehabilitation program.

Access to healthcare isn’t just a matter of having good insurance coverage. In many cases, it can mean finding the time to see all of the different clinicians involved in providing comprehensive care, or securing transportation to appointments. These studies suggest that online interventions can provide effective therapy while overcoming common real-world challenges to accessing care.

Using a blood marker to predict accelerated brain atrophy in MS

Neurofilament light chain, or NfL, is a protein expressed by neurons. NfL levels in the cerebrospinal fluid and blood rise when there is damage to axons, the cable-like projections that extend out from neurons to transmit electrical impulses to other neurons, muscles, and glands. Because increased levels of NfL indicate axonal damage, researchers have focused in recent years on how to track MS disease activity and progression by measuring serum NfL.

One of the latest studies in this area examined an association between elevated blood levels of NfL and the rate of brain atrophy in people with MS.13 Investigators at healthcare institutions in the United States and other countries measured serum NfL levels in 201 healthy people who do not have MS. They used that data to establish age-specific norms for NfL. They then applied those norms to 2,443 people with MS, and categorized those with blood levels of the protein greater than the 97.5th percentile for their age to have elevated serum NfL.

People with MS who had elevated serum NfL had a higher rate of whole brain atrophy on magnetic resonance imaging than people with MS with lower levels of the protein: a decrease of 0.22% per year vs. a loss of 0.15% per year. The difference between those figures was statistically significant. Investigators reported that the accelerated rate of atrophy was seen across age groups and MS subtypes, in men and women, and regardless of MS duration.

While studies such as these do not drive specific changes in current treatment strategies, they play a valuable role in expanding researchers’ understanding of the MS disease process and in identifying new areas of focus for the development of new medications.

Diagnostic duo helps differentiate MS from its mimics

Diagnosing multiple sclerosis correctly and in a timely manner can be challenging because several other conditions cause the same or similar symptoms.

In working to enhance the diagnostic process, researchers have evaluated many magnetic resonance imaging (MRI) findings, substances in the blood and cerebrospinal fluid, and other tests to see which are most useful in distinguishing MS from other conditions. Two of the most promising MRI-related candidates are the identification of lesions located in the cerebral cortex (cortical lesions, or CLs) and the so-called central vein sign (CVS) – a vein that shows up as a dot or thin line in the center of a lesion identified on MRI T2 sequences and that runs through all or part of the lesion.

A group of researchers from 13 MS centers in Canada and Europe recently examined the diagnostic accuracy of those two measures individually and in combination.14  The investigators had two separate raters assess 927 MRI scans, including 559 from people diagnosed with MS or its frequent precursor, clinically isolated syndrome (CIS), and 368 from people with other conditions, including cerebrovascular disease, migraine, neuroinflammatory conditions other than MS, and normal aging.

The researchers reported that an MRI finding of one or more cortical lesions had 60% sensitivity and 93% specificity for MS/CIS. This means that 60 out of 100 people who have one or more cortical lesions will have MS or CIS, while 93 out of 100 who do not have a cortical lesion will not have MS/CIS. Meanwhile, people with MS/CIS had a higher percentage of CVS-positive lesions than did those with other conditions. According to the study’s authors, when the two measures were considered together, their ability to correctly identify MS/CIS was increased. They concluded that “high diagnostic performance can be reached by combining CLs and CVS.”

References

  1. Bridge F, Brotherton J, Stankovich J, et al. High efficacy disease-modifying therapies increase the risk of cervical abnormalities in women with multiple sclerosis. Mult Scler. 2022; 28: (3S) 3-129. O089.

  2. Kalincik T, Sharman S, Roos I, et al. for the MSBase Study Group. Comparative effectiveness of autologous haematopoietic stem cell transplantation vs. fingolimod, ocrelizumab, and natalizumab in relapsing-remitting MS. Mult Scler. 2022; 28: (3S) 3-129. O019.

  3. Zarghami A, Fuh Ngwa V, van der Mei I, et al. Longitudinal transitions of employment status after a first episode of CNS demyelination. Mult Scler. 2022; 28: (3S) 3-129. O152.

  4. Knowles S, Middleton R, Cooze B, et al. The demographics, clinical course, and pathology of late-onset MS. Mult Scler. 2022; 28: (3S) 3-129. O066.

  5. Fox RJ, Wiendl H, Wolf C, et al. Assessment of dose dependency of anti-inflammatory and neuroprotective efficacy variables and biomarkers for vidofludimus calcium in EMPhASIS: a randomized, placebo-controlled phase 2 trial in relapsing-remitting multiple sclerosis. Mult Scler. 2022; 28: (3S) 3-129. O120.

  6. Graham E, Bakkensen J, Anderson A, et al. Relapse risk after fertility treatments in women with MS: a multicenter analysis of inflammatory activity. Mult Scler. 2022; 28: (3S) 3-129. O040.

  7. Schwake C, Steinle J, Thiel S, Ciplea AI, Gold R. Effects of anti-CD20 therapies on infant health and physiological B-cell development if administered before or during pregnancy and/or lactation. Mult Scler. 2022; 28: (3S) 3-129. O036.

  8. Forsberg L, Dormont F, Hillert J, Glaser A. Short-term change in disability and processing speed, but not relapse rate, predicts health-related quality of life five and ten years later. Mult Scler. 2022; 28: (3S) 3-129. O014.

  9. Finnegan T, Arnaud-Hevi L, Jones E, et al. Online medical education reveals differences between neurologists and PCPs on knowledge, competence, and confidence of the impact of race and ethnicity in multiple sclerosis. Poster presentation at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Amsterdam, The Netherlands: October 26, 2022.

  10. Taul-Madsen L, Kristensen NM, Gaemelke T, Dalgas U, Hvid LG. Identifying multiple sclerosis fallers by neuromuscular function. Mult Scler. 2022; 28: (3S) 3-129. O086.

  11. Gold SM, Friede T, Meyer B, et al. Online intervention to reduce depressive symptoms in multiple sclerosis: an international multicenter randomized controlled Phase III trial. Mult Scler. 2022; 28: (3S) 3-129. O115.

  12. Yavas I, Kahraman T, Sagici O, et al. Effects of telerehabilitation-based pelvic floor muscle training on urinary incontinence, sexual dysfunction, and quality of life in people with multiple sclerosis: a randomised, controlled, assessor-blinded trial. Mult Scler. 2022; 28: (3S) 3-129. O116.

  13. Sotirchos E, Fitzgerald K, Singh C, et al. Serum neurofilament light chain is associated with longitudinal brain atrophy across patient subgroups in MS. Mult Scler. 2022; 28: (3S) 3-129. O168.

  14. Cagol A, Cortese R, Barakovic M, et al. A multicentric investigation of the diagnostic accuracy of cortical lesions and central vein sign in multiple sclerosis. Mult Scler. 2022; 28: (3S) 3-129. O095.

For More Information

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.

Written by Tom Garry, Medical Writer
Reviewed by Dr. Barry Hendin, MSAA Chief Medical Officer
Edited by Susan Wells Courtney, MSAA Senior Writer