What’s New in MS Research: January 2019

Throughout the year we hear of new insights into the causes, consequences, and management of multiple sclerosis (MS), as well as progress in translating those scientific findings into enhanced patient care. The time since the last edition of “What’s New in MS Research” has been no exception, with several important studies being published in the closing months of 2018 and the first days of 2019. This installment of “What’s New in MS Research” highlights the breadth of that research, as the nine studies reported below examine everything from a possible link between food allergies and MS disease activity, to the promise of stem cell transplantation in people who have not obtained a satisfactory response from multiple disease-modifying therapies (DMTs). Important studies on the potential causes of MS, the role of patient preferences in drug selection and adherence, and other topics also are covered.

Exploring a link between food allergies and MS disease activity

People with MS who have food allergies have a higher rate of relapses and of MRI-identified disease activity than those with MS who have no known allergies.

That was the main finding of a study of 1,349 people with MS participating in an ongoing study at Brigham and Women’s Hospital in Boston. [Fakih 2018] Based on their responses to a questionnaire, study participants were assigned to one of four groups: people with environmental allergies, food allergies, drug allergies, or no known allergies (NKA). Investigators then assessed each group in terms of number of MS relapses/attacks, Expanded Disability Status Scale (EDSS) score, MS Severity Score (MSSS), and presence of gadolinium-enhancing lesions and lesion count on MRI.

No significant differences emerged between people who reported environmental or drug allergies as well as those with no known allergies. However, the food allergy group had a 2.5-fold greater likelihood of having gadolinium-enhancing lesions on MRI relative to those who did not have food allergies, and a 1.38 times greater rate for cumulative number of relapses. Researchers did not find an association between allergies and EDSS or MSSS scores.

The study’s authors concluded, “Future prospective studies are needed to confirm our findings and investigate underlying biological mechanisms, which may unveil new therapeutic and preventative strategies for MS.”

Increased prevalence of asthma among people with MS

Asthma is three times more common in people with multiple sclerosis (MS) than in the general population, according to a study that analyzed health data for more than 56 million people. [Hill 2018]

Investigators from the Case Western Reserve University School of Medicine drew on electronic health record (EHR) information to identify the prevalence of asthma in 141,800 people with MS and more than 56 million other people in the United States.

They found that the three-fold greater presence of asthma among people with MS was relatively consistent regardless of gender or race. Asthma also was more prevalent in people with MS when subjects were analyzed by age. However, the researchers found a U-shaped distribution by age group: the prevalence of asthma was higher in people with MS who were either younger than 30 years old, or who were 80 years of age and older, than in middle-aged people with MS. Among people who do not have MS, the prevalence of asthma varies far less by age.

The researchers noted that their findings underscore the need for identifying and managing comorbidities (conditions other than MS that an individual may experience) in providing comprehensive MS care. The findings also suggest the importance of people with MS reporting any respiratory issues to their healthcare providers rather than dismissing shortness of breath, wheezing, or similar symptoms as just arising from “being out of shape” or “having a lingering cold.”

Do household chemicals increase children’s risk for multiple sclerosis?

This topic is often addressed since it is a question parents frequently ask after their child has been diagnosed with a serious condition.

In recent years, researchers have made considerable progress in providing partial or potential answers to the question as it pertains to pediatric-onset multiple sclerosis (MS). The latest contribution to that effort comes from a study conducted by investigators at 16 institutions belonging to the United States Network of Pediatric Multiple Sclerosis Centers (NPMSC). [Mar 2018] The researchers found that indirect or passive exposure to three types of household chemicals was associated with an increased risk of children developing MS.

The investigators drew on comprehensive questionnaires completed by parents. The forms had questions about a wide range of topics, including indirect or passive exposure (i.e., living in a home where a substance was present, as opposed to handling or ingesting the substance) to 13 types of household chemicals. The questionnaires yielded data on 312 children diagnosed with MS or clinically isolated syndrome and 490 healthy children who served as case controls. The majority of the patients studied were females, and the median age of subjects with MS or CIS was 15.7 years, while that for the healthy children was 15.0 years. Researchers adjusted for participants’ age, sex, race, ethnicity, and other factors to eliminate imbalances between the two groups that could skew the results.

The study found that household exposure to certain rat and mouse poisons or weed-control agents was associated with a doubling of risk for pediatric-onset MS. Meanwhile, household exposure to certain products used to control plant and tree disease was associated with a 2.7-fold increased risk for developing MS or CIS as a child.

The investigators emphasized that while their research suggested an association between household exposure and increased risk, “future studies are needed to elucidate a causal relationship and the exact agents involved.”

Less sun exposure early in life means greater MS risk later

A study examining subjects from Canada, Italy, and Norway found that low sun exposure before 16 years of age increases the risk of later-life multiple sclerosis (MS) by almost 50 percent compared with people with high exposure to the sun. [Magalhaes 2018]

The research drew on data from 2,251 people with MS and 4,028 healthy controls participating in the Environmental Risk Factors In MS (EnvIMS) case-control study. People with the lowest reported exposure to the summer-time sun during their childhood and early adolescence had a 1.47-fold greater risk of later being diagnosed with MS than those who reported the highest amount of time spent outdoors during the summer.

The study also found that people with the lowest overall exposure to sun – encompassing summer and winter exposure and high use of sun protection agents and clothing – had a 76-percent higher risk of developing MS compared with those with high sun exposure and low use of sun protection.

This study builds on earlier research suggesting an association between low sun exposure and increased risk of MS. Its findings further strengthen the case for enhancing children’s health and wellbeing by having them spend more time outdoors (although the results should not be interpreted as diminishing the importance of applying sunblock and taking other steps to avoid sunburn). The study did not address the issue of Vitamin D blood levels, which are determined in part by sun exposure. Correlating children’s sun exposure with Vitamin D levels and risk for MS later in life may be an important next focus for this fascinating line of scientific inquiry.

The treatment goal that matters most to people with MS

Brain health is the top treatment goal of people with MS, followed by impact on disability, and symptom management, according to a recent study of 135 adult patients. [Col 2018]

Study participants used an online tool to outline their thoughts and preferences regarding treatment goals, attributes of disease-modifying therapies (DMTs), and factors shaping a decision to change treatment approaches. Their reported preferences were compared to findings from an earlier study. Participants also were asked to assess the usefulness of the online tool.

The DMT attributes that mattered most to participants were treatment effectiveness, serious side effects, and quality of life, while the top factors in changing treatment were disease progression or relapses, learning about different treatments, and difficulty handling treatment. Those findings were consistent with the results of the earlier study to which they were compared.

Eighty-seven percent of participants said they wanted to talk with their clinician about their treatment goals and priorities, but 37 percent said that they do not routinely do so. Almost all of the participants indicated that the tool helped them understand their treatment goals and preferences and appropriately summarized their priorities. The study’s authors noted that the tool “could potentially be used to help patients communicate their preferences to their clinician.”

What drives non-adherence to disease-modifying therapies (DMTs)? Surprising findings

One might assume that there is a natural relationship between degree of treatment satisfaction and extent of adherence to disease-modifying therapy (DMT). Natural, but incorrect, according to the results of a study involving almost 500 people with MS. [Thach 2018]

Surprisingly, the research found that neither treatment satisfaction nor beliefs about medication were significantly associated with DMT adherence. Rather, results showed that younger age, taking an injectable DMT, and experience with past DMTs, were risk factors for not taking a disease-modifying therapy as often as prescribed. While the association between younger age and risk for non-adherence was modest, that association was more pronounced for prior experience with DMTs and, particularly, for use of an injectable DMT.

Most of the respondents were white (93.8 percent) and women (86.6 percent). The average age of study participants was 60.5 years. Two-thirds took an injectable DMT, and more than 92 percent were considered adherent to therapy, which was defined as taking prescribed medication 80 percent or more of the time in the prior two weeks. Beyond reporting their medication use, participants provided demographic information and completed questionnaires about their satisfaction with the treatment they were taking and their beliefs about medicine.

The authors noted that it would be important to assess the impact that various factors have on DMT adherence in more diverse groups of people with MS. [Desai 2019]

Examining factors in use of oral vs. injectable DMTs

Patient and physician preference, rather than clear-cut clinical factors, apparently is driving a shift from injectable to oral agents in people initiating or switching disease-modifying therapies (DMTs), according to a study of more than 8,900 people with MS. [Desai 2019]

The analysis examined data on commercially insured patients in the United States who started or changed a DMT regimen between 2009 and 2014. More than 7,500 of the patients studied initiated a DMT in that period, while 1,342 switched DMTs.

In 2011, just 5 percent of patients studied began DMT therapy with an oral agent, but by 2014, that proportion had increased 7-fold to 35 percent. Similarly, in 2011, 16 percent of patients changing DMTs switched to an oral agent, but three years later, 84 percent of patients were choosing an oral therapy when changing DMTs.

The investigators examined several clinical factors (such as specific symptoms, disease activity, and other co-existing conditions) to see which might be associated with the use of oral DMTs. Just two factors — a recent neurologist consultation and a visit to an emergency department — were significantly associated with starting an oral DMT. None of the clinical factors examined were associated with switching to an oral agent.

The authors concluded, “We identified few factors predictive of oral DMT initiation or switching, which implies that their selection is driven by patient and/or physician preferences.”

For people who have failed multiple treatment therapies, stem cell transplant may be promising

A small study suggests that stem cell transplantation can combat relapses and improve outcomes in people with MS who have significant disability and who have failed a number of disease-modifying therapies (DMTs).

Researchers in Australia followed 35 people for a median of three years after those patients received transplants of their own blood-producing stem cells. These cells had been removed and stored before the patients underwent chemotherapy to deplete their immune cells and essentially “reboot” their immune system. [Moore 2018] Twenty of the patients had relapsing-remitting MS (RRMS), and 15 had secondary-progressive MS (SPMS). The study participants had taken an average of four DMTs before transplant, with some patients having taken as many as seven DMTs. Similarly, the group’s median Expanded Disability Status Scale (EDSS) score was 6, where some type of assistance – such as a cane or crutch – is needed to walk 100 meters.

After three years, 60 percent of all patients and 70 percent of those with RRMS had no clinical or radiographic evidence of relapse, and no worsening of disability. Forty-four percent had sustained improvement in their EDSS score. No treatment-related deaths occurred.

This was a single-center, relatively small Phase II trial with no control group. Nonetheless, the outcomes it achieved over three years in this group of patients (who had high EDSS scores and already had been treated with several DMTs) offers hope to people with relatively advanced MS. These results will likely spur further research into the stem cell transplantation protocol that was used in this study.

A call (literally) to exercise: Study supports effectiveness of telerehabilitation in MS

People with MS who exercised at home under the supervision of a physical therapist, communicating with them on an audio/visual platform, realized the same benefits as their counterparts who traveled to a medical facility for in-person physical therapy (PT).

That’s the finding of a small, 30-patient study conducted to evaluate the feasibility of “telerehabilitation” for people with MS. [Fjeldstad-Pardo 2018] The prospective study randomly assigned 30 people with MS who had ambulatory problems to one of three groups. The first group participated in a customized but unsupervised home-based exercise program five days per week. The second group engaged in twice-weekly physical therapy, supervised by a remotely located therapist who used audio and video to guide the patients. The third group had twice-weekly physical therapy supervised by a therapist at a medical facility. Researchers evaluating individual participants’ progress did not know which patient had been assigned to which group.

After eight weeks, all three groups saw improvements in gait function. As assessed by a variety of measures, no significant difference was found between the telerehabilitation group that had twice-weekly PT and either the patients who exercised at home five days per week in an unsupervised fashion or the people who had twice-weekly in-person supervised PT. The study authors concluded that telerehabilitation “is a feasible method to perform PT in persons with MS and has comparable efficacy to conventional in-person PT as measured by patient reported outcomes and objective outcomes of gait and balance.”

While in-person PT sessions are the ideal arrangement for those who are able to take advantage of such services, these findings suggest an expanded ability to provide PT services to people with MS who may have trouble accessing PT in-person. Typical challenges include the amount of distance they live from the medical facility as well as transportation issues.

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.

Edited by Susan Wells Courtney, MSAA Senior Writer

References:

Col NF, Solomon AJ, Springmann V, et al. Evaluation of a novel preference assessment tool for patients with multiple sclerosis. Int J MS Care. 2018 Nov-Dec;20(6):260-267. doi: 10.7224/1537-2073.2017-021.

Desai RJ, Mahesri M, Gagne JJ, et al. Utilization patterns of oral disease-modifying drugs in commercially insured patients with multiple sclerosis. J Manag Care Spec Pharm. 2019 Jan;25(1):113-121. doi: 10.18553/jmcp.2019.25.1.113.

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Moore JJ, Massey JC, Ford CD, et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 Dec 11.pii: jnnp-2018-319446. doi: 10.1136/jnnp-2018-319446.

Sanchirico M, Caldwell-Tarr A, Mudumby P, Hashemi L, Dufour R. Treatment patterns, healthcare resource utilization, and costs among Medicare patients with multiple sclerosis in relation to disease-modifying therapy and corticosteroid treatment. Neurol Ther. 2018 Dec 18.doi: 10.1007/s40120-018-0123-y.

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