disease progression

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Navigating Roadblocks with SPMS

I saw my neurologist earlier this week. After my work-up, we sat and discussed how well I manage my multiple sclerosis. How well? No comment. Suffice it to say this disease is a worthy adversary. I have been feeling a little funky since that appointment. I have been looking to…

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DMTs Are Cost-Effective and Help to Slow MS Progression, 10-Year Study from UK Reports

Four disease-modifying therapies (DMTs) for  multiple sclerosis — Avonex, Rebif, Betaferon, and Copaxone — are cost-effective and reduce disease progression in MS patients, especially those with relapsing-remitting disease, according to 10-year, real-world results from U.K.’s MS Risk Sharing Scheme (RSS). But the long-term benefits observed wane over…

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Lymphatic Vessels of Brain Carry Messages That Appear to Promote MS, Study Reports

Lymphatic vessels, the “roads” that work to clear waste material from the brain, can also carry messages that direct immune system attacks against myelin, promoting the onset of multiple sclerosis (MS), new study shows. While the identity of these messages remains unknown, the findings suggest that blocking these signals could…

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Phase 3 Trial in UK Soon to Test Statin, Simvastatin, in Slowing SPMS Progression

A large Phase 3 trial getting underway at sites across the U.K. will test the effectiveness of simvastatin, a widely used oral statin, in possibly treating secondary progressive multiple sclerosis (SPMS), the study’s sponsor, University College of London Hospitals (UCLH), announced. The study, the largest ever undertaken for SPMS…

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Ocrevus Increases Proportion of PPMS Patients with No Disease Progression or Activity, Phase 3 Trial Shows

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.

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Truly ‘Benign MS’ Evident in Only Small Minority of Patients, Large UK Study Reports

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.”

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Ocrevus Predicted to Be a Billion-dollar Blockbuster

Ocrevus, a disease-modifying MS treatment that’s only been on the market a little less than 18 months, appears poised to be a cash cow for its maker, Genentech. The research firm Spherix Global Insights, which analyzes trends in the pharmaceutical industry, predicts that Ocrevus is “poised to…

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Everywhere I Go, I’m Invited To ‘Take a Seat’

I knew I had MS nine years ago when I went back to see my neurologist. I’d had the lumbar puncture to prove it definitively, and I displayed all the requisite symptoms. The only question I had was, “Will this lead to me being in a wheelchair?” The…

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Deciding if Ocrevus Is Right When You’re Over 55

As a 61-year-old woman diagnosed in 2010 with primary progressive multiple sclerosis (PPMS), I was overjoyed when the U.S. Food and Drug Administration (FDA) approved the therapy Ocrevus (ocrelizumab) in March 2017. Because Ocrevus is the first treatment approved to possibly slow the progression of PPMS, the FDA’s green…

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Long-term DMT Use Seen to Lower Likelihood of RRMS Progressing to SPMS in Study

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…

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MS Lesions and Silent Inflammation

Multiple sclerosis (MS) consists of more than lesions; it also comprises silent inflammation. Lesions seem to get all the attention, as they are photographed and flashy, and the main topic in MS circles. But silent inflammation is what is running the havoc behind the scenes. The MS Society…