March 21, 2019 News by Jose Marques Lopes, PhD Roche and pan-Canadian Pharmaceutical Alliance Finalize Ocrevus Negotiations for RRMS and Early PPMS Roche Canada and the pan-Canadian Pharmaceutical Alliance (pCPA) have completed negotiations ultimately aiming to obtain public funding for Ocrevus (ocrelizumab) as a first-line treatment for adults with relapsing-remitting multiple sclerosis (RRMS) with active disease, and as management strategy for patients with early primary progressive MS…
March 19, 2019 Columns by Ed Tobias DMT Choice for Your MS Is Your Decision About 15 disease-modifying therapies (DMTs) are available to treat MS these days. So, choosing which to use can be daunting. I’ve been treated with four DMTs since I was first prescribed Avonex (interferon beta-1a) back in 1996. Each time I’ve switched treatments, my neurologist has suggested a number of…
March 18, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: Non-contrast MRIs, Stem Cell Study Seeks Subjects, Postpartum Relapses, Which DMT? Non-contrast MRI Effective in Monitoring Progression of MS, Study Shows There’s been increased interest in the risks versus the benefits of using gadolinium to make lesions more visible on an MRI. The U.S. Food and Drug Administration issued an advisory last year raising the level of…
March 5, 2019 Columns by Ed Tobias Two Different Approaches to Providing Online MS Help I received an email recently from the National Multiple Sclerosis Society in the U.S. promoting a searchable database of “credible doctors and resources.” A few days later, I happened to run across another online multiple sclerosis (MS) information service hosted by the HealthCare Journey website. They call it…
March 1, 2019 News by Jonathan Grinstein #ACTRIMS2019 ā Use of Ocrevus at Cleveland Clinic Backs Phase 3 Trial Data Ocrevus (ocrelizumab) was shown to be aĀ highly effective therapy for people with multiple sclerosis (MS) in real-world clinical practice, according to Brandon Moss, MD, from theĀ Cleveland Clinic. The data was presented in a poster session Feb. 28, atĀ the Americas Committee…
February 18, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: Misdiagnosing MS, Gilenya Relapse Study, Ocrevus in England, Estimate of Americans with MS Doubles Almost 1 in 5 People Wrongly Diagnosed with MS at Two Specialized Centers in US, Study Finds We know that MS is a difficult disease to diagnose, but is it really possible that 20 percent of the MS diagnoses are wrong? Apparently so. This study reports that…
February 11, 2019 News by Jonathan Grinstein Petition Urges NHS England to Make Ocrevus Available for PPMS Patients More than 21,000 people have signed a petition calling for Ocrevus (ocrelizumab) to be made available by the National Health Service (NHS) in England for people with primary progressive multiple sclerosis (PPMS). According to anĀ MS Trust press release, the…
February 8, 2019 Columns by Ed Tobias DMT Approvals for Medicare Users Decline While Costs Rise, Study Shows This probably won’t come as a surprise to you if you’re on Medicare: It’s getting harder to obtain approval for many of the disease-modifying therapies (DMTs) prescribed for people with multiple sclerosis (MS). I see complaints about this all the time on social media. Now, research reported in…
February 5, 2019 Columns by Ed Tobias Have You Joined Our MS Forums Yet? It’s been about nine months since we created the MS Forums section on the Multiple Sclerosis News Today website. It’s a placeĀ designed to host conversations about our MS experiences and to find some answers from reliable sources when you have a question. You can even begin your own…
January 25, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: HSCT vs. DMTs, Mindfulness for MS, Ocrevus and T-cells, Pregnancy Guidelines Blood Stem Cell Transplant Better than DMTs at Reducing Risk of Disease Progression in RRMS Here’s more evidence that hematopoietic stem cell transplant (HSCT) works better than some disease-modifying therapies (DMTs) at reducing multiple sclerosis (MS) progression. In this study, only three of 52 patients in the…
January 24, 2019 Columns by Tamara Sellman Need to Know: The Link Between the Epstein-Barr Virus and MS Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about multiple sclerosis? Visit our forum. This week’s question is inspired by the forum topicĀ “Can there be a connection between Epstein-Barr virus…
January 15, 2019 News by Jose Marques Lopes, PhD Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, āOcrelizumab Depletes CD20+Ā T Cells in Multiple Sclerosis Patients,ā was published in the journal Cells. AutoreactiveĀ immune T-cells, which attack the bodyās own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy isĀ Genentechās Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid ā the liquid surrounding the brain and spinal cord ā and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximabĀ (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatmentĀ that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximabās clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical SchoolĀ in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patientsā peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease forĀ a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes ā white blood cells that include T- and B-cells ā and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cellsā fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. āOur results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,ā the researchers wrote. āThese findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,ā they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.
January 7, 2019 Columns by Debi Wilson My MS Column in Review: The Topics that Resonated with Readers At the beginning of each year, I reflect on the one that has just passed. In this column, I’m looking back on my multiple sclerosis (MS) columns from 2018, at some of the most popular topics, and how they affect those of us with MS. My columnās year…
January 2, 2019 News by Jose Marques Lopes, PhD Top 10 Multiple Sclerosis Stories of 2018 Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, andĀ clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…
December 18, 2018 News by Jose Marques Lopes, PhD Pretreating Ocrevus Patients with Multiple Antihistamines and Liquids Lowers Infusion Reactions by 60%, Study Reports PretreatingĀ multiple sclerosisĀ patients withĀ antihistamines more extensively and with hydration can significantly reduce ā by 60% ā the likelihood ofĀ infusion-associated reactions that are the most common side effect of Ocrevus (ocrelizumab) use, a pilot study reported. Data also found that older and male MS patients are less likely to have…
December 12, 2018 News by Alice MelĆ£o, MSc Ocrevus Now Available Through NHS Scotland to Treat RRMS Ocrevus (ocrelizumab, by Genentech) is now available through the National Health System (NHS) of Scotland to treat patients with relapsing-remitting multiple sclerosis (RRMS). The decision by the Scottish Medicines Consortium (SMC) to approve Ocrevus’ inclusion for this patient group follows theĀ recommendationĀ made earlier by the U.K.ās…
December 11, 2018 Columns by Ed Tobias Consensus Lacking on How MS Medications Are Prescribed in the UK Living in the U.S., where disease-modifying therapies (DMTs) seem to be prescribed as a matter of course to people with multiple sclerosis (MS), I was surprised that it doesn’t seem to be the case across the pond in the U.K. An article just published on the Multiple…
November 19, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: New Thinking About MS Development, Rhythm to Improve Walking, UK Nurse Shortage, B-cells MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development Our immune system, according to this study, may not be the only thing playing a role in the development of our MS. The same cells that produce the myelin that coats our nerves may also be…
November 16, 2018 Columns by John Connor And the Good News Is … Getting started on any career is fraught with difficulty, and the trail that got me to my base camp was truly meandering. It was nearly as convoluted as that sentence! At 23, without meaning to, I found myself being a putative theater critic. Within months, under the pressure of…
November 15, 2018 News by Jose Marques Lopes, PhD Ocrevus Helps Preserve Hand and Arm Function in PPMS Patients, Trial Data Show TreatingĀ primary progressive multiple sclerosis (PPMS) patients with Ocrevus (ocrelizumab) can help to preserve strength and function in their hands and the arms, analysis of data from a Phase 3 trial found. The research, āOcrelizumab reduces progression of upper extremity impairment in patients with primary progressive…
November 8, 2018 Columns by Jennifer (Jenn) Powell MS and Your Immune System: ‘Tis the Season for the Flu Fall is my favorite season. I love the change in temperature, the falling of amber leaves, trading flip-flops for loafers, the din of football games, and the joy of the holiday season. There is so much to enjoy, yet this particular Sunday I am sick. I have acquired the…
November 5, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Ocrevus in the UK, Environmental Triggers, PPMS Research NICE Postpones Final Opinion on Adding Ocrevus to Public Health System for PPMS Patients in UK This last-minute reprieve from the agency that dictates which medications may be prescribed for patients of the U.K.’s National Health Service (NHS) is welcome news. Last summer, the National Institute for…
November 2, 2018 News by Vijaya Iyer, PhD NICE Postpones Final Opinion on Adding Ocrevus to Public Health System for PPMS Patients in UK A final and weighty opinion regarding whetherĀ Ocrevus (ocrelizumab)Ā will be among treatments available at low or no cost to primary progressive multiple sclerosis (PPMS) patients in England and Wales ā through the National Health Service (NHS) āĀ has been put on hold, according to the Multiple Sclerosis Trust. The…
October 24, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Ocrevus Used Early in MS Course Key to Slowing Disability, Genentech Director Says Treating patients withĀ primary progressive or relapsing multiple sclerosis (MS) early with Ocrevus (ocrelizumab) is key to slowing disease progression, according to Hideki Garren, global head of Multiple Sclerosis and Neuroimmunology at Genentech. In an interview withĀ Multiple Sclerosis NewsĀ TodayĀ at the recentĀ 34thĀ congress of the European Committee for Treatment…
October 16, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Evobrutinib and Other Reasons for Hope in Pursuit of MS Treatments, Jerry Wolinsky Says in Interview Advances in multiple sclerosisĀ research and the development of new treatments over the last several decades give sustained reasons for hope as continue moving toward our future, according toĀ Jerry S. Wolinsky, a neurologist and MS specialist whose career spans more than 40 years. In a wide-ranging interview with Multiple…
October 4, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Genentech to Present Ocrevus-related MS Studies at Conference Treatment with Ocrevus (ocrelizumab) over five years lessened upper limb disability progression in primary progressive multiple sclerosis (PPMS) patients, reduced relapses and brain disease activity in patients with relapsing MS, and helped achieveĀ no evidence of disease progression (NEDA) in a greater proportion of African-descent patients, compared to treatment…
September 28, 2018 Columns by Ed Tobias Serious DMTs Need Serious Care Coordination Ocrevus (ocrelizumab) is a serious disease-modifying therapy. It has the potential to deliver a major blow to a patient’s MS, but it also carries the possibility ofĀ severe side effects. The protocol for Ocrevus requires different doses on different infusion dates, following a specific treatment schedule. It’s also…
September 24, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Treating MS with a Statin, Ocrevus, Remyelination Phase 3 Trial in the UK Soon to Test Statin, Simvastatin, in Slowing SPMS Progression I’ve taken a statin medication for years to keep my cholesterol in check. Now, a study is getting underway to see if one statin pill can also be used to treat MS. It’s particularly…
September 21, 2018 News by Alice MelĆ£o, MSc Ocrevus Climbing as First-line DMT for RRMS Among Neurologists Surveyed in Spherix Report Eighteen months after its entrance into the U.S. market,Ā Genentechās 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 theĀ third quarter of 2018 surpassed…
September 13, 2018 News by Jose Marques Lopes, PhD Ocrevus Increases Proportion of PPMS Patients with No Disease Progression or Activity, Phase 3 Trial Shows TreatingĀ primary progressive multiple sclerosisĀ patients with OcrevusĀ (ocrelizumab)Ā led to a three-fold increase in the proportion of those showing no evidence of disease progression and no signs of inflammatory disease activity over more than two years of treatment, results of a Phase 3 trial show, and support new measures that might better capture disability in PPMS patients. The research, āEvaluation of No Evidence of Progression or Active Disease (NEPAD) in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Trial,ā was published in the journal Annals of Neurology. Measuring disease progression in clinical trials and clinical practice requires reliable and comprehensible measures. Although widely used, the Expanded Disability Status Scale (EDSS, range 0-10) cannot fully capture changes in walking speed and hand or arm function, which are key determinants of overall disability in progressive forms of MS. No evidence of progression (NEP) is a newer measure that reflects the absence of disability progression, including upper limb function and walking speed. Maintaining NEP status means stable disease with no worsening in EDSS, in walking ability (assessed by the Timed 25-Foot Walk (T25FW) test, or the time it takes to walk 25 feet as quickly and safely as possible), and in upper limb function (assessed by the 9-Hole Peg Test (9HPT), a test of arm and hand dexterity). Patients with PPMS have less frequent signs of disease activity, which include relapses and brain lesions (assessed though magnetic resonance imaging or MRI). So scientists proposed a new measure ā called āno evidence of progression or active diseaseā (NEPAD) ā to evaluate both NEP and clinical and MRI measures of active disease. The researchers believe that NEPAD may represent a more sensitive and comprehensive measure of disease control in PPMS patients. The randomized, double-blind ORATORIO Phase 3 trial (NCT01194570) analyzed the efficacy and safety of Ocrevus ā developed byĀ Genentech, part of theĀ RocheĀ group ā in 732 PPMS patients (age range 18ā55). Results showed that Ocrevus treatmentĀ delayed the relative risk of disability progression by 25% compared to placebo, while also reducing the volume of chronic brain lesions and total brain volume loss. As a result, Ocrevus became the first therapy approved by the U.S. Food and Drug Administration and the European Commission for both PPMS and relapsing MS. Now, researchers assessed Ocrevusā effect in PPMS patients included in the Roche-funded ORATORIO study using as trial goals changes in NEP and NEPAD. These people received either 600 mg of Ocrevus or placebo by intravenous (IV) infusion every six months for a minimum of 120 weeks (about 2.3 years). The trialās main goal was time to onset of clinical disability progression (CDP) sustained for at least 12 weeks. CDP was defined as a 1.0 point or greater increase in EDSS score from a baseline (study start) score of 5.5 or less, or a 0.5-point increase from a baseline score greater than 5.5. NEP status, analyzed in 230 placebo- and 461 Ocrevus-treated patients, was defined as no evidence of CDP for 12 weeks, no 20% or more change in hand/arm function as measured by the 9HPT for 12 weeks, and no 20% or more change in walking ability as measured by the T25FW test for 12 weeks.Ā "The 20% cut-off for progression on the T25FW test and the 9HPT has previouslyĀ been shown to be a clinically meaningful magnitude of disease progression," the study noted. In turn, NEPAD ā assessed in 234 placebo- and 465 Ocrevus-treated patients ā included NEP, no brain MRI-measured disease activity, and no relapses.Ā Relapses were defined as new or worsening neurological symptoms attributable to MS lasting longer than 24 hours and preceded by neurological stability for a minimum of 30 days. Brain MRI scans were conducted at baseline, and weeks 24, 48, and 120; new or enlarging T2 lesions and/or T1 enhancing lesions were considered evidence of MRI disease activity (T1 MRI imaging offers information about current disease activity by highlighting areas of active inflammation, while a T2 MRI image provides information about disease burden or lesion load). Overall, the majority of the PPMS patients analyzed experienced clinical disease progression or evidence of disease activity. From baseline to week 120, Ocrevus-treated patients who achieved NEP (42.7% of 461 people) or NEPAD (29.9% of 465) Ā ā no disease activity or progression ā were found to have lower T2 brain lesion volume and a lower EDSS score (lesser disability) compared to those with evidence of MS progression. They also had a slightly superior performance on the 9HPT and the T25FW test. Patients who reached NEPAD also showed fewer T1 lesions than patients with progressing or active disease. Compared to placebo treatment, the proportion of Ocrevus-treated PPMS patients maintaining NEP or NEPAD from baseline to week 120 was higher ā for NEP, 42.7% versus 29.1% in the placebo group; for NEPAD, 29.9% versus 9.4% in the placebo group. These results showed that Ocrevus treatment increased theĀ proportion of PPMS patients with NEPAD throughout the 120 weeks of the study by three-fold. āIn conclusion, ocrelizumab (Ocrevus) increased the proportion of patients with PPMS with no evidence of progression and no clinical and subclinical disease activity compared with placebo,ā the team wrote. āAs such, NEPAD may represent a meaningful and comprehensive disease outcome in patients with PPMS.ā However, data from ORATORIO's open-label extension and real-world data are needed to "determine whether NEPAD maintained throughout 120 weeks will translate intoĀ sustained NEPAD and enhanced protection against accrual of disability in patients with PPMS overĀ the long term," the researchers concluded. Of note, five of the studyās 11 authors are employees and/or shareholders of Roche or Genentech.