RRMS

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…

Measuring the response of the pupil to light stimulating the eye is a non-invasive and easy way to assess multiple sclerosis (MS) severity and progression, researchers report. A clinical study found that poor, or dysfunctional, pupil response was associated with longer disease duration and greater disease severity in relapsing-remitting multiple…

Levels of neurofilament light chain are a reliable predictor of disease worsening and progression in relapsing-remitting MS (RRMS) patients, a new study shows. Moreover, treatment with Gilenya (fingolimod), marketed by Novartis, can reduce the levels of NfL for up to 10 years. These findings were shared recently in the presentation “…

Long-term treatment with Ocrevus (ocrelizumab)  — as well as switching from Rebif (interferon beta-1a) to Ocrevus — leads to a significant and sustained reduction in disease activity in relapsing forms of multiple sclerosis (MS). These previously reported findings are further supported by the latest results drawn from pooled data…

Gilenya (fingolimod) and Tecfidera (dimethyl fumarate) are equally effective as first-line treatments in people with relapsing-remitting multiple sclerosis (RRMS), but Gilenya may be of slightly more benefit to those who switch from a previous injectable therapy, according to a real-world study of patients in Italy. The study, “…

Young adults with multiple sclerosis (MS) have higher relapse rates and respond better to Gilenya treatment compared to the overall MS population, data from a post hoc analysis of three separate trials show. The study, “Relapse Rate and MRI Activity in Young Adult Patients With Multiple…

Alkermes announced that it has received a $50 million payment from Biogen after a review of preliminary data related to the gastrointestinal tolerability of BIIB098 (diroximel fumarate), now in pivotal clinical studies as a possible treatment for relapsing forms of multiple sclerosis (MS). BIIB098, formerly known as ALKS 8700…

Patients with active relapsing-remitting multiple sclerosis (MS) continue to show improvement — lesser functional disability across a variety of measures — and often without the need for continuous treatment after taking Lemtrada for two years, according to six-year results from the CARE-MS II extension study. These results were shared in a…

New results from a Phase 2 trial evaluating TG Therapeutics’ ublituximab continue to support the therapy’s efficacy in treating relapsing forms of multiple sclerosis (MS). This investigative infusion therapy is now moving into a Phase 3 study. Treatment with 450 mg of ublituximab delivered intravenously in a rapid fashion…

Age at disease onset, number of early relapses, and the extent of brain damage at baseline can help identify those who are at high risk of progression from relapsing-remitting multiple sclerosis into the secondary progressive phase of the disease, a new study shows. The study with that finding, “…

Treatment with Gilenya (fingolimod) is associated with treatment satisfaction, which, in turn, is linked to a better quality-of-life in patients with relapsing-remitting multiple sclerosis (RRMS), a study has found. Gilenya, an oral disease-modifying treatment (DMT) for RRMS developed by Novartis, has been available in France since 2011. Studies have…

A formulation of ofatumumab (brand name Arzerra) to be injected under the skin (subcutaneous) was found to be safe and effective in the treatment of relapsing-remitting multiple sclerosis (RRMS), even when given at lower doses…

Rituximab is generally safe and effective in treating multiple sclerosis — with comparable effectiveness to Tysabri (natalizumab) in people with relapsing-remitting forms of the disease, a Swiss study reports. But patients using this therapy can develop recurrent infections, its researchers noted, and doctors should be vigilant. The observational study, “…

A Johns Hopkins University-initiated clinical trial is starting to enroll an estimated 900 relapsing-remitting multiple sclerosis (RRMS) patients to assess the benefits of switching therapies to prevent or reduce disability. The TREAT-MS study (NCT03500328) will evaluate whether RRMS patients with disease activity while on a traditional first-line disease-modifying therapy…

After an agreement to lower their prices, four treatments for relapsing multiple sclerosis — Biogen’s Avonex and Merck KGaA‘s Rebif (both interferon beta-1a), Novartis’ Extavia (interferon beta 1b), and Teva’s Copaxone (glatiramer acetate) — were recommended as cost-effective and long-term therapy options within the National Health Service…

Gilenya (fingolimod) has become the first disease-modifying therapy approved by the U.S. Food and Drug Administration (FDA) to treat children and adolescents with relapsing forms of multiple sclerosis (MS). This expanded approval allows Gilenya, previously indicated for adults patients 18 or older, to be used to treat pediatric relapsing MS…

An approved lymphoma treatment, rituximab was found to be effective and safe for relapsing-remitting multiple sclerosis (RRMS) patients whose active disease has failed to respond to immunosuppressive therapies, a retrospective French study reports. Published in the Multiple Sclerosis Journal in an article titled, “Efficacy of…

One thing we’ve all hoped for with our disease-modifying therapies (DMT) is a treatment that will improve our multiple sclerosis (MS) and not just keep it from worsening. The latest studies presented on Ocrevus (ocrelizumab) hold promise that this treatment may have finally arrived. According to recent reports,…

An additional analysis of data from the CLARITY study confirmed the long-term benefits of treatment with Mavenclad (cladribine tablets) for patients with highly active relapsing forms of multiple sclerosis (MS). The post-hoc analysis, “Efficacy of Cladribine Tablets in high disease activity subgroups of patients…

Lemtrada (alemtuzumab) can sustain reduced activity and prevent progression of relapsing-remitting multiple sclerosis (RRMS) for more than seven years, clinical data from the CARE-MS extension trial shows. Findings were recently presented in four poster presentations at the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles. Lemtrada, marketed by Sanofi Genzyme, is an approved MS therapy that, according to its label, should generally be reserved for patients who have had an inadequate response to two or more other therapies. But the use of the word "generally" opens a window of opportunity “to use Lemtrada as a second-line therapy and potentially first-line therapy,” Barry Singer, MD, director of the MS Center for Innovations in Care at Missouri Baptist Medical Center, said in an email response to questions from Multiple Sclerosis News Today. The treatment was initially tested in two pivotal clinical trials in comparison with a high-dose under-the-skin injection of Rebif (interferon beta-1a) in RRMS patients. Participants were either new to treatment (CARE-MS I, NCT00530348) or had not responded to prior therapies (CARE-MS II, NCT00548405). During these trials, patients received 12 mg of Lemtrada for three or five consecutive days in two annual courses — at the beginning of the study and again one year later. After completing this treatment period, they had the opportunity to participate in a four-year extension study (NCT00930553) during which they could receive the therapy as needed to control their disease. Patients completing the extension could enroll in the five-year TOPAZ trial (NCT02255656) for further evaluation. To date, 80% of the participants (299 patients) from CARE-MS I and 73% from CARE-MS II (317 patients) have completed seven years of long-term follow-up. After completing two initial courses of Lemtrada, 59% of patients from CARE-MS I and 47% from CARE-MS II did not require additional treatment courses with Lemtrada or other disease-modifying therapies during the next six years. Two-thirds of  CARE-MS II patients who required a third Lemtrada course also experienced disability stabilization one year after the last treatment. During the seven years of follow-up, reported annualized relapse rates remained low, and 37% of patients from CARE-MS 1 and 44% from CARE-MS II experienced confirmed improvements in disability. In fact, during this period, only 26% from CARE-MS 1 and 31% from CARE-MS II showed disability worsening. The treatment also had a sustained effect on slowing brain volume loss by the seventh year, with a median yearly brain volume loss of 0.20% or less from the third to seventh year. This effect was found to be even better than that reported during the initial two years of treatment in the pivotal studies (0.59% in the first year and 0.25% in the second year in CARE-MS I, and 0.48% in year one and 0.22% in year two in CARE-MS II). Additionally, evaluation by magnetic resonance imaging (MRI) showed no signs of disease activity during the seven years of follow-up. “The extension study data being presented at AAN illustrate that more than two-thirds of patients did not experience confirmed disability worsening at year seven after initiating treatment with Lemtrada,” Singer said in a press release. “In addition, consistent effects were maintained over time across relapses and MRI outcomes including brain volume loss, even though the majority of patients did not receive any additional treatment over the prior six years.” During the extension studies, the frequency of adverse events was similar to that reported during the pivotal studies. In seven years, three deaths occurred, none of which was considered to be treatment-related. Thyroid adverse events were reported to be more frequent by the third year, but declined thereafter. As Singer noted, "the serious risks of Lemtrada, including serious infusion reactions, serious infections, thyroid disease, kidney disease, low platelets and potential malignancies, must always be discussed with the patient." All patients should also be carefully monitored on a monthly basis for four years after the last treatment course “to screen for autoimmune complications, including low platelet counts, thyroid disease, and kidney disease,” he said. Lemtrada’s long-term effects were shared at the AAN annual meeting in these presentations: “Active RRMS Patients Treated with Alemtuzumab Experience Durable Reductions in MRI Disease Activity and Slowing of Brain Volume Loss: 7-Year Follow-up of CARE-MS II Patients (TOPAZ Study)” “Durable Clinical Outcomes With Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS II Patients (TOPAZ Study)” “Durable Reduction in MRI Disease Activity and Slowing of Brain Volume Loss in Alemtuzumab-Treated Patients With Active RRMS: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study)” “Durable Clinical Efficacy of Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study) Lemtrada is approved in more than 60 countries, and has additional marketing applications under review by regulatory authorities worldwide.

Treatment with Ocrevus (ocrelizumab) is linked to a reduced immune response to vaccinations in patients with relapsing multiple sclerosis (MS), according to a Phase 3 trial. These results were recently presented at the 2018 American Academy of Neurology (AAN) Annual Meeting in Los Angeles in a presentation titled, “Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis.” Genentech’s Ocrevus is an approved MS therapy that targets the CD20 protein located on the surface of B-cells, targeting the cells for destruction. B-cells are immune system cells involved, for example, in the production of antibodies necessary to fight off infection. At the AAN meeting, researchers reported that in MS patients, treatment with Ocrevus decreased the ability of B-cells to activate other immune cells, improving the rate of MS attacks. Penn Medicine neurologist Amit Bar-Or, MD, presented these findings, which showed that interactions between different classes of immune cells, such as B- and T-cells, promote MS attacks. Vaccination against infections is an important part of the management of patients with MS. So, in a second study (NCT02545868), researchers investigated the impact treatment with Ocrevus has on patient response to vaccines. They recruited 102 patients with relapsing MS and randomized them in two groups. In group A, 68 people received a single dose of 600 mg Ocrevus (administered into the blood); in group B, 34 patients received no disease-modifying therapy or interferon-beta. All patients were then administered vaccines for tetanus, seasonal flu, and pneumococcus. Patients in group A received the vaccines 12 weeks after they were treated with Ocrevus, while group B patients received the vaccines on day one. Researchers also tested patients’ response to a novel protein (an antigen) never "seen" by their immune system, called keyhole limpet hemocyanin (KLH) neoantigen. The vaccinations led to an immune system response in all patients, but the level of response in patients treated with Ocrevus was lower. A positive response to the tetanus vaccine at eight weeks after treatment was 23.9% in group A (Ocrevus) compared with 54.5% in group B (no treatment); the response to pneumococcus vaccination was 71.6% in group A and 100% in group B. After four weeks of treatment, the levels of antibodies against the different strains of the flu virus were lower in Ocrevus-treated patients than in the control group, ranging from 55.6% to 80.0% in the Ocrevus group compared with 75.0% to 97.0% in the controls. The immune response to the neoantigen KLH was also decreased in the Ocrevus group. "This study shows that while people with MS treated with ocrelizumab [Ocrevus] can still mount vaccine responses, it's not nearly as strong as prior to treatment," Bar-Or said in a press release. "While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level," he said. "This is valuable information in terms of seasonal vaccines such as the flu — it appears safe for patients taking ocrelizumab to get vaccinated and vaccination is likely to provide them with at least some protection from such infections." These findings correlate with standard guidelines that advise patients to undergo vaccinations six weeks before they start treatment with Ocrevus.

Cladribine treatment leads to a selective depletion of memory B-cells in patients with relapsing-remitting multiple sclerosis (RRMS), researchers report. The results are in the presentation “Cladribine for the Effective Control of Multiple Sclerosis via Memory B Cell Depletion” being given Friday, the final day of the 2018 Annual Meeting of the …

Multiple sclerosis in African-Americans progresses much faster than in Caucasian patients, new research reports, suggesting that blacks would benefit from a more aggressive treatment approach. Led by researchers at Johns Hopkins University and presented at the American Academy of Neurology (AAN) annual meeting taking place in Los Angeles through…

A one-year analysis of the ongoing Phase 3 EVOLVE-MS-1 trial of ALKS 8700 as a therapy for relapsing remitting multiple sclerosis (RRMS) supports the experimental therapy’s effectiveness, with the treatment significantly reducing the number of MS lesions. Interim results from the trial were presented Tuesday at the…

Celgene’s oral treatment candidate ozanimod can effectively reduce relapse rates in multiple sclerosis (MS) patients with mild to moderate disability, results of two Phase 3 trials show. The company will present data on the SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) trials in two presentations at the…