RRMS

The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency (EMA), has recommended that Gilenya (fingolimod) be approved to treat children and adolescents, ages 10 to 17, with relapsing-remitting multiple sclerosis (RRMS). If the CHMP opinion is accepted, Gilenya — marketed by…

Eighteen months after its entrance into the U.S. market, Genentech’s Ocrevus (ocrelizumab) has become the monoclonal antibody of choice to treat patients with multiple sclerosis (MS), according to a survey of nearly 100 neurologists across the U.S. Self-reported use of Ocrevus for the third quarter of 2018 surpassed…

Two years of treatment with oral Gilenya (fingolimod) significantly reduced the rate of relapses when compared to Avonex (interferon beta-1a) intramuscular injections in children and adolescents with relapsing forms of multiple sclerosis (RMS), according to Phase 3 clinical trial results. Additionally, Gilenya (marketed by Novartis) decreased the number of central nervous…

A study of Iranian patients with early-onset multiple sclerosis (MS) found women to be in the majority, optic neuritis to be the most common first disease symptom, and relapsing-remitting MS the most frequent disease course. The epidemiology of early-onset MS (typically, MS diagnosed before age 16; age 18 was the benchmark…

Multiple sclerosis (MS) that appears to be "genuinely benign" 15 years after diagnosis is evident in a small number of patients, a large population-based study from the U.K. reports. But, its researchers note, the term “benign” is often not clinically accurate as used, because it is based largely on perceptions of disease impact. The study “How common is truly benign MS in a UK population?” was published in the Journal of Neurology, Neurosurgery & Psychiatry. The concept of benign MS is controversial, especially among clinicians. Still, long-term epidemiological studies have consistently identified a small fraction of patients whose MS progresses very slowly over a long span of years. Determining the prevalence of this type of MS in the population has been difficult, as estimates can vary significantly depending of the definition of “benign” that is adopted. Researchers sought to determine an accurate estimate of benign MS in the U.K. population, using a rigorous and comprehensive clinical definition of a truly benign disease. This definition included minimal physical disability (EDSS score of less than 3), and no significant fatigue, mood disturbance, cognitive impairment or interrupted employment in the absence of treatment with disease-modifying therapies over 15 years or more years after symptom onset. They screened an U.K. population-based registry containing data on 3,062 MS patients to identify those with "unlimited walking ability" 15 or more years after diagnosis. A representative sample of 60 patients  from this pool was analyzed (45 women and 15 men, mean age of 57); they had a mean disease duration of 28 years. Nine out of these 60 (15%; 8 women and one men) fulfilled the study’s criteria for truly benign disease. These nine people had a mean age of 27 at symptom onset, a median EDSS disability score of 1.5 (minimal signs of disability), and a mean disease duration of 31 years. "Those nine individuals with truly benign MS all remained in a relapsing–remitting state," the study noted. "However, only two out of nine showed disease arrest within the first decade; the remainder all continued to experience relapses well into their second or third decade of MS," but the rates of such relapses were low. MS in the remaining patients was not classified as benign, mostly due to evidence of cognitive difficulties (57%), and the disease's impact on employment status (52%) with many taking early retirement. Based on these results, a population frequency for "benign MS" under the definitions used was estimated at 2.9%. But the researchers noted that a large proportion of patients (65%; 39 patients out of 60) reported their disease as benign, according to a lay definition. Their self-reported status poorly agreed with the clinical assessments done throughout the study. "There is no accepted definition to offer patients when exploring whether they feel their MS is benign; the definition we chose incorporates the fundamental principles of low impact on a person, absence of complications and a favourable outcome and is in line with definitions provided by third-party support groups," the researchers wrote. Many  considering themselves with benign disease did so based on their "perception" of their disease, the team added, and one that "appeared to be driven as much by mood, fatigue and bladder function as by physical ability."  “In conclusion, after detailed clinical assessment, a small minority of people with MS appear genuinely unaffected by symptoms after 15 years,” the researchers added. They also called attention to the fact that EDSS-based definitions of benign MS and the inconsistency between patient and clinician perception of benign MS compromise the use of the term ‘benign’ in clinical practice. They also emphasize that studying individuals with benign MS “has the potential to uncover clues to mechanisms underlying favorable outcomes in MS, provide insights into new therapeutic targets and have implications for patient counselling, individual patient management and the construct of clinical trials.”

Tysabri (natalizumab) was reported in a small retrospective study to significantly improve cognitive abilities in people with relapsing-remitting MS patients (RRMS) over two years of use. The study, “Improvement in Cognitive Function as Measured by NeuroTrax in Patients with Relapsing Multiple Sclerosis Treated with Natalizumab: A 2-Year…

Adults in Ireland with highly active relapsing multiple sclerosis (MS) now can be treated with Mavenclad (cladribine tablets, 10 mg), the first short-course oral treatment approved for this disease. The Irish Health Service Executive (HSE) has approved this new therapy and decided to reimburse patients for its associated…

Poor sleep quality is very common among patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome (CIS), and is associated with a lower quality of life, and greater fatigue, depression and anxiety, according to a real-world study in patients treated with Betaferon (interferon beta-1b). The study, “…

Gilenya (fingolimod) influences the release and function of small membrane particles, called extracellular vesicles, that are involved in the development of multiple sclerosis — and these vesicles may serve a biomarker of treatment effectiveness in people with relapsing MS, researchers report. Extracellular vesicles (EVs) may also work…

Abreos Biosciences announced the U.S. launch of moNATor, a laboratory-developed test that can help physicians monitor the levels of Tysabri (natalizumab) in patients with multiple sclerosis (MS). Tysabri (approved for relapsing forms of MS, by Biogen) administered at a dose of 300 mg every four weeks is known to be…

The levels of three small, regulatory RNA molecules — long non-coding RNAs — are deregulated in blood samples of patients with relapsing-remitting multiple sclerosis (RRMS), a study reports. The long non-coding RNAs are involved in the regulation of the natural immune response and DNA-damage response, supporting the theory that these…

Long-term treatment with disease-modifying therapies (DMTs) appears to lessen the risk of disease worsening in relapsing-remitting multiple sclerosis (RRMS) patients, an 18-year follow-up study suggests. But these therapies were not seen to benefit those who had progressed to secondary progressive multiple sclerosis (SPMS). The study, “Onset of secondary…

Hair Loss Seen in RRMS Patients Using Aubagio Often Temporary and Mild, Study Says I read a lot of questions on multiple sclerosis (MS) social media groups from people who are worried about hair loss caused by their disease-modifying therapy (DMT). Aubagio (teriflunomide) is one DMT with…

Hair thinning in relapsing-remitting multiple sclerosis (RRMS) patients using Aubagio is usually mild and temporary, and does not require stopping treatment, a small real-world study reports. The research, “Real-World Observational Evaluation of Hair Thinning in Patients with Multiple Sclerosis Receiving Teriflunomide: Is It an Issue in Clinical…

TG Therapeutics announced it has reached target enrollment in the ULTIMATE I and II Phase 3 clinical trials assessing the use of ublituximab (TG-1101) to treat relapsing forms of multiple sclerosis (MS). Ublituximab is a modified anti-CD20 monoclonal antibody, which is designed to target a protein present on mature…

Smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis being treated with Tysabri , an observational study suggests. Multiple sclerosis is a multifactorial disease associated with both genetic and environmental risk factors. Smoking, in particular, has been linked to numerous aspects of MS, including its development and progression. In a previous study, the research team looked at how smoking influences the relapse rate in RRMS patients being treated with interferon beta. From more than 800 patients, they found that smoking one pack per day (about 20 cigarettes) essentially interfered with the positive effect of the IFN-beta treatment and increased the relapse rate by 27%. The researchers then questioned whether the same was true for other treatments. Tysabri, developed by Biogen, is a monoclonal antibody that targets the alpha-4 integrin protein. By interfering with this molecule, the therapy prevents white blood cells from moving into the central nervous system, suppressing the immune reaction that contributes to MS symptoms. In the study, 355 Tysabri-treated RRMS patients from the Danish Multiple Sclerosis Centre were assessed. To gather information on smoking habits and body mass index, the patients filled out a 100-question survey. Data was collected between the start of the treatment and a two-year follow-up visit. Results showed that smoking one pack of cigarettes per day increases the relapse rate by 38% in RRMS patients on Tysabri. This increase in relapse rate takes into account both sex and age at the start of treatment, since age can affect the relapse rate. For example, an increase in age by one year raises the number of relapses by 2%. The researchers also looked at the relationship between smoking and the presence of two immune-related alleles: HLA-DRB1*15:01 and HLA-A*02:01. Previous studies showed that HLADRB1*15:01 is associated with an increased risk of developing MS, while HLA-A*02:01 is linked to a decreased risk. Although previous studies reported a link between smoking and these two alleles in MS patients, the current study did not find an association between smoking and carrying either of these alleles. Based on the results, the researchers concluded that smoking significantly increases the relapse rate in RRMS patients receiving Tysabri. According to the team, the results "add important information that hopefully will sharpen the focus on the overall harmful effects of smoking in MS patients."

Pendopharm’s Glatect (glatiramer acetate injection), a lower cost alternative to Teva’s Copaxone, has been added to the public health plans of five Canadian provinces for patients with…

Loss of health-related quality of life is caused mostly by balance problems, muscle stiffness, and depression in people with relapsing-remitting multiple sclerosis (RRMS), and for those with progressive MS, the causes are muscle rigidity, paralysis, weakness, and pain, according to a…

Being treated with ozanimod consistently reduced disease activity in people with relapsing-remitting multiple sclerosis (RRMS), according to results of a two-year extension of a Phase 2 trial. These benefits were evident both in patients on continuous treatment throughout the study, and in those who switched to ozanimod from placebo. Results…

Seven years after it first denied the request, the U.S. Food and Drug Administration accepted for review EMD Serono’s resubmitted New Drug Application (NDA) for cladribine tablets (brand name Mavenclad) as a treatment for patients with relapsing forms of multiple sclerosis (MS). The regulatory agency agreed EMD…

African-Americans with relapsing–remitting multiple sclerosis (RRMS) show higher adherence and greater satisfaction when treated with oral Gilenya (fingolimod, by Novartis) than with injectable therapies, according to a new study. The research, “Treatment retention on fingolimod compared with injectable multiple sclerosis therapies in African-American patients: A…

Oral disease-modifying therapies (DMTs) are the most common first choice of treatment for people newly diagnosed with multiple sclerosis (MS) in the United States, an analysis reports. Antibody-based DMTs like Ocrevus, however, are emerging competitors. Spherix Global Insights, a market research and analysis company, states that 1 in every…

In women with relapsing-remitting multiple sclerosis (RRMS), there is a significant increase in brain lesion volume after pregnancy, but it is not accompanied by a loss of brain cells, a study suggests. Conducted by researchers at Harvard Medical School, the study, “Quantitative MRI analysis of cerebral lesions and…

Cerebrospinal fluid levels of neurofilament light chain, a protein associated with nerve cell damage, can predict disease progression in people with clinical isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS), a Swedish study found. Higher levels…

Shortening the washout period to four weeks when switching from Biogen’s Tysabri to Novartis’ Gilenya is safe and reduces the chances of experiencing a disease flare in patients with relapsing-remitting multiple sclerosis (RRMS), a small Swiss study found. A four-week washout reduced the risk of having a disease relapse or an increase in disease activity, compared with an eight-week washout period, for two years after switching from Tysabri to Gilenya. Although Tysabri effectively slows worsening of MS symptoms and the appearance of disease flares, its use is under a strict risk management plan as it heightens the risk of developing a rare and life-threatening brain infection called progressive multifocal leukoencephalopathy, also known as PML. Some patients may switch to Gilenya, an alternative disease-modifying therapy for RRMS. Gilenya has been associated with a lower risk of PML infection and seen to reduce relapses, disability worsening, and the appearance of new brain lesions on clinical trials. It also is the only therapy approved by the U.S. Food and Drug Administration for children with MS as young as 10. When switching from Tysabri to Gilenya, it is important to consider the washout period, which is the period when the patient is taken off medications. If too long, it may lead to disease reactivation, which can be even stronger than before starting Tysabri. There is little evidence about the optimal length of washout periods, but a Phase 3 trial showed that an eight-week washout between Tysabri and Gilenya was beneficial compared with longer washouts of 12 or 16 weeks. The eight-week washout enabled more RRMS patients to become free from relapses and lowered disease activity. To study if a shorter washout period of four weeks further reduced the risk of MS reactivation, researchers conducted an open-label, observational study at the University Hospital, Basel, Switzerland. The study enrolled 25 RRMS patients who were appointed to switch from Tysabri to Gilenya. Participants were assigned to either a four-week or an eight-week washout period, and were followed for two years after switching to Gilenya. Although patients were older in the four-week washout group, disease activity and disability scoreswere not significantly different between groups at the beginning of the study. Relapses, disability scores, and disease activity on magnetic resonance imaging scans were recorded at baseline and weeks 8, 12, 16, 20 32, 56, and 108. In the first year (week 56) the proportion of patients with disease flare-ups or disease activity on MRI was not significantly different between the two washout groups, affecting 55.6% and 62.5% of the patients who had a four-week and an eight-week washout, respectively. However, at the end of the two-year follow-up (week 108), recurrent event analysis showed that patients who were on the four-week washout group were 77% less likely to experience relapses. The combined risk for relapse or disease activity on MRI also was 58% lower in the four-week group, compared with those who had an eight-week washout. In addition, researchers found that patients who had flares more frequently in the year before discontinuing Tysabri also had a nearly four times higher risk of experiencing relapses in the first year after switching to Gilenya. This suggests that the number of relapses before switching from Tysabri can predict disease reactivation once on other disease-modifying therapies. Both washout periods were deemed safe, with no serious adverse side effects or cases of opportunistic infections, including PML, being reported. Researchers emphasized, however, that the findings need to be confirmed in larger studies.

Missouri Trial to Examine if Fasting Alters Gut Microbiome and Immune System of RRMS Patients in Helpful Ways The impact of various diets on multiple sclerosis (MS) has been studied, but this new study will look into whether fasting has an impact. The researchers at Washington University…

A 12-week clinical study is recruiting people with relapsing-remitting multiple sclerosis (RRMS) to evaluate if intermittent fasting can improve their immune response, metabolism, and gut microbiome — the bacterial community that inhabits the gastrointestinal tract. Its findings may also hint at whether such a diet might ease MS symptoms or alter discourse course and, if used in conjunction with other treatments, boost their efficacy. Conducted by researchers at Washington University in St. Louis, Missouri, the trial is supported by their findings in an earlier mouse study.  Results showed that fasting worked to ease MS-like symptoms in a mouse model of the disease, the research team reported. Specifically, EAE mice fed every other day were less prone to symptoms that included difficulty in walking, limb weakness, and paralysis than mice allowed to eat freely.  A fasting diet also enriched bacterial diversity in the mice guts, and shifted immune cell populations there toward a lower inflammatory response. When gut bacteria were transferred from fasting mice to nonfasting mice, the later also were seen to be better protected against MS-like movement problems, supporting the influence of the gut microbiome on MS symptoms. Several diets have been proposed to help ease disease progression in MS patients, but solid scientific evidence is lacking to support any one diet over another, leaving the issue much to an individual’s choice. “The fact is that diet may indeed help with MS symptoms, but the studies haven’t been done,” Laura Piccio, MD, an associate professor of neurology at WUSTL and the study's lead author, said in a WUSTL news release written by Tamara Bhandari. Taking place at the Missouri university, the trial is expected to enroll 60 RRMS patients. Half will be randomly assigned to eat a standard Western-style diet seven days a week, and the other half to Western-style diet five days a week, with two days set aside for fasting (consuming a maximum of 500 calories each day). On fasting days, patients can only drink water or calorie-free beverages and eat fresh, steamed or roasted non-starchy vegetables All will undergo a neurological assessment, and provide blood and stool samples in the study's beginning, at mid-point or week six, and at its end (week 12). Those using MS medications will continue on their prescribed treatment regimens throughout the study. More information, including enrollment information, is available here. Piccio noted that a pilot study on diet in 16 MS patients showed that limiting calories every other day for two weeks led to immune and gut microbiome changes that resembled those observed in the mice study she helped to lead. Its researchers concluded that intermittent fasting had the potential to positively manipulate the immune response in MS patients by changing their gut microbiome. The gut microbiome plays a central role in digestion, and in producing vitamins and amino acids (the building blocks of proteins). But a growing body of evidence indicates that it also determines how our immune systems develops and matures. Indeed, an increasing number of studies link irregularities in the gut microbiome with MS. “There are several possible ways fasting can affect inflammation and the immune response,” Piccio said. “One is by changing hormone levels. We found that levels of the anti-inflammatory hormone corticosterone were nearly twice as high in the fasting mice. But it also could act through the gut microbiome.” The new trial will allow the team to analyze more deeply the effects of a fasting diet — and perhaps gather evidence for a larger study investigating if skipping meals can ease MS symptoms. Its goal is to find out "whether people on limited fasts undergo changes to their metabolism, immune response and microbiome similar to what we see in the mouse,” Piccio said. “I don’t think any physician working with this disease thinks you can cure MS with diet alone,” she added, “but we may be able to use it as an add-on to current treatments to help people feel better.”

People with relapsing-remitting multiple sclerosis in Denmark show high rates of adherence to treatment with Gilenya (fingolimod), and give the therapy high marks in terms of satisfaction and quality of life, a long-term study of its use by RRMS patients reports. The study, “High treatment adherence, satisfaction, motivation,…

Relapsing-remitting multiple sclerosis (RRMS) patients with active disease may now be treated with Ocrevus (ocrelizumab, developed by Genentech) within the National Health Service (NHS) — the subsidized public health system that covers England and Wales. But those in Scotland will not. The National Institute for Health and…

New retrospective analysis of the Phase 3 CLARITY study (NCT00213135) shows that treatment with Mavenclad (cladribine tablets) improved annualized relapse rate and magnetic resonance imaging (MRI) outcomes in patients with relapsing-remitting multiple sclerosis (RRMS), regardless of their age. Moreover, the effectiveness of Mavenclad was comparable to five standard therapies…