ocrelizumab

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…

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…

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…

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…

Ocrevus (ocrelizumab) was shown to be a highly effective therapy for people with multiple sclerosis (MS) in real-world clinical practice, according to Brandon Moss, MD, from the Cleveland Clinic. The data was presented in a poster session Feb. 28, at the Americas Committee…

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…

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 an MS Trust press release, the…

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…

It’s been about nine months since we created the MS Forums section on the Multiple Sclerosis News Today website. It’s a place 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…

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…

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 topic “Can there be a connection between Epstein-Barr virus…

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, “Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients,” was published in the journal Cells. Autoreactive immune T-cells, which attack the body’s 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 is Genentech’s 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 — the liquid surrounding the brain and spinal cord — and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximab (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatment 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 rituximab’s 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 School 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 patients’ 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 for 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 — white blood cells that include T- and B-cells — and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cells’ 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. “Our 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,” the researchers wrote. “These 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,” they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.

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 column’s year…

Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, and 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…

Pretreating multiple sclerosis patients with antihistamines more extensively and with hydration can significantly reduce — by 60% — the likelihood of 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…

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 the recommendation made earlier by the U.K.’s…

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…

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…

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…

Treating 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, “Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive…

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…

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…

A final and weighty opinion regarding whether Ocrevus (ocrelizumab) will be among treatments available at low or no cost to primary progressive multiple sclerosis (PPMS) patients in England and Wales — through the National Health Service (NHS) — has been put on hold, according to the Multiple Sclerosis Trust. The…

Treating patients with 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 with Multiple Sclerosis News Today at the recent 34th congress of the European Committee for Treatment…

Advances in multiple sclerosis research and the development of new treatments over the last several decades give sustained reasons for hope as continue moving toward our future, according to Jerry S. Wolinsky, a neurologist and MS specialist whose career spans more than 40 years. In a wide-ranging interview with Multiple…

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 achieve no evidence of disease progression (NEDA) in a greater proportion of African-descent patients, compared to treatment…

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 of severe side effects. The protocol for Ocrevus requires different doses on different infusion dates, following a specific treatment schedule. It’s also…

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…

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…

Treating primary progressive multiple sclerosis patients with Ocrevus (ocrelizumab) 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, “Evaluation of No Evidence of Progression or Active Disease (NEPAD) in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Trial,” 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 — called “no evidence of progression or active disease” (NEPAD) — 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 — developed by Genentech, part of the Roche group — in 732 PPMS patients (age range 18–55). Results showed that Ocrevus treatment 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 Ocrevus’ 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 trial’s 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. "The 20% cut-off for progression on the T25FW test and the 9HPT has previously been shown to be a clinically meaningful magnitude of disease progression," the study noted. In turn, NEPAD — assessed in 234 placebo- and 465 Ocrevus-treated patients — included NEP, no brain MRI-measured disease activity, and no relapses. 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)  — no disease activity or progression — 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 — 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 the proportion of PPMS patients with NEPAD throughout the 120 weeks of the study by three-fold. “In 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,” the team wrote. “As such, NEPAD may represent a meaningful and comprehensive disease outcome in patients with PPMS.” However, data from ORATORIO's open-label extension and real-world data are needed to "determine whether NEPAD maintained throughout 120 weeks will translate into sustained NEPAD and enhanced protection against accrual of disability in patients with PPMS over the long term," the researchers concluded. Of note, five of the study’s 11 authors are employees and/or shareholders of Roche or Genentech.