September 11, 2018 News by Ana Pena PhD

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.”

May 17, 2018 News by Jose Marques Lopes, PhD

Impact of Early Aggressive vs. Standard Therapy on Disability in RRMS To Be Tested in Trial

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…

May 2, 2018 News by Alice Melão, MSc

#AAN2018 — Lemtrada Sustains Long-Term Benefits for RRMS Patients, TOPAZ Study Shows

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.

April 27, 2018 News by Alice Melão, MSc

#AAN2018 – Stem Cell Transplant is Effective Treatment for ‘Aggressive’ MS, Study Shows

Autologous hematopoietic stem cell transplantation, also known as aHSCT, has been shown to be safe and highly effective to treat patients with "aggressive" multiple sclerosis. Tested in 19 patients, transplantation of stem cells was found to induce clinically meaningful improvements in disability. These findings were shared at the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles, California. aHSCT uses a patient’s own healthy bone marrow stem cells, in combination with a much less aggressive chemotherapy and/or radiation regimen, to prepare the patient for the transplant. Previous studies have suggested that aHSCT is an effective strategy to treat patients with highly active relapsing-remitting MS (RRMS) who do not respond to available disease-modifying therapies (DMTs), and international guidelines advocate for its use in patients with "aggressive" MS. To further demonstrate the potential of aHSCT as a treatment for "aggressive" MS, a research team evaluated its safety and effectiveness in MS patients who had not been treated previously with DMTs. A total of 19 patients were treated across several clinical centers: seven patients were from Sheffield, U.K., seven from Uppsala, Sweden, four from Ottawa, Canada, and one patient was from Florence, Italy. All patients received aHSCT between May 2004 and May 2017. In addition to aHSCT, patients were treated with BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy plus antithymocyte globulin (ATG) to reduce transplant rejection, or with Cytoxan (cyclophosphamide) with ATG, or the triple combination of Cytoxan, ATG, plus busulfan as conditioning regimens. Patients had a median age of 33 years at diagnosis and received the aHSCT by a median time of nine years after symptom onset. They had a median disability score of 6.5 before the treatment, as determined by the Expanded Disability Status Scale (EDSS). After a median follow-up period of 30 months, patients had a median EDSS score of 2.0, which represented a median improvement of 2 points (the higher the score, the worse the patient's disability level). None of the patients had clinical relapse following the transplant of stem cells. Only three patients developed new brain lesions detectable by magnetic resonance imaging (MRI) at the first six-month follow-up evaluation, but no additional new lesions were detected in the following scans. The adverse effects reported during the study were comparable to those previously observed in similar treatments. No deaths related to the treatment were reported. Based on these preliminary results, the researchers concluded that aHSCT is “safe and highly effective in inducing rapid and sustain remission” in highly active MS, and "was associated with a significant improvement of [patient’s] level of disability.” “aHSCT should be considered as first line therapy in patients with ‘aggressive’ MS,” the team concluded. Another study presented at the AAN 2018 meeting further supports these findings, demonstrating the superior effectiveness of aHSCT over conventional DMTs for RRMS.

April 23, 2018 News by Patricia Inacio, PhD

#AAN2018 – Blood Stem Cell Transplant Superior to DMDs in Highly Active RRMS, MIST Trial Shows

Autologous non-myeloablative hematopoietic stem cell transplant was found to be significantly better at reducing risks for disability in relapsing-remitting multiple sclerosis (RRMS) patients compared to disease-modifying drug (DMD) therapies, interim results of the MIST clinical trial show. The results will be shared at the 2018 Annual Meeting of the American…

April 16, 2018 Columns by Debi Wilson

When Did Showering Become Such a Thrill Ride?

My morning ritual of showering for a fresh start to my day has progressed to a once-a-week occurrence. Like everything else that my multiple sclerosis (MS) affects, less shower time is not by choice. I take sponge baths daily of course, but actual showers are reserved for when I…

March 21, 2018 Columns by Cathy Chester

Teach Your Children Well

As an advocate for the multiple sclerosis community, people often ask me what it’s like being a mother while living with MS. My quick response is, “Joyous!” But I understand the questioner is looking for something more. They want to know how to…

March 21, 2018 News by Patricia Inacio, PhD

Blood Stem Cell Transplants Improve RRMS Patients’ Disability, Phase 3 Trial Shows

Blood stem cell transplants lead to significant improvements in relapsing-remitting multiple sclerosis patients’ disability, a Phase 3 clinical trial shows. The 110 patients who took part in the MIST study (NCT00273364) were having relapses after receiving standard therapies such as beta interferon, Copaxone (glatiramer acetate), Novantrone (mitoxantrone), Tysabri (natalizumab), Gilenya (fingolimod),…

March 14, 2018 News by Alice Melão, MSc

National MS Society to Award $433,800 to Support 10 Pilot Research Projects

The National Multiple Sclerosis Society will award $433,800 to 10 high-risk pilot studies that will quickly evaluate new strategies and interventions and enhance knowledge about multiple sclerosis (MS). According to a press release, the award winners will address different aspects of the disease, including potential treatments for fatigue and loneliness, to improve patients' walking abilities, and a strategy to change gut bacteria effects in MS. The year-long Pilot Research Grant program is a way to support early-stage research projects to quickly test their effectiveness. The MS Society also said that additional projects will be awarded this year. Results of a recent survey of approximately 300 pilot grant recipients revealed the program successfully promotes new ideas and brings new researchers to the MS field. About 90 percent of the respondents agreed that the financial support was very important for their research project. In 85 percent of cases, the grant supported new ideas, and in 56 percent it allowed support for additional grants. These pilot grants allow researchers to obtain preliminary data so they can decide to apply for additional funding, if the project looks  promising, or to put the idea to rest.

March 14, 2018 Columns by Judy Lynn

Why I Climb Trees

In March 2003, I found myself suddenly unable to drive or even walk a straight line through the house. MS had arrived with several active lesions in my brain, including one in the brainstem, which affected my balance and speech and created significant limitations in my usual activities. One…

March 1, 2018 News by Alice Melão, MSc

Argentina Approves Mavenclad for Active Relapsing MS

Argentina has become the first country in Latin America to approve Mavenclad (cladribine) as a treatment for adults with highly active relapsing multiple sclerosis. The Argentinian Administration of Medicines, Food and Medical Technology's approval covered Merck’s cladribine tablet formulation. Merck expects to make the treatment available in the country in the next few months. Mavenclad has already been approved in Canada, Australia, Israel, and Europe. Merck is seeking approval in the United States and other countries. "Having a new MS treatment approved in Argentina is very motivating," Dr. Jorge Correale of the Institute for Neurological Research Dr. Raúl Carrea said in a press release. "Mavenclad allows the patient's immune system to go through a selective immune reconstitution, similar to a reset, and the treatment mechanism is simple because it does not require frequent administration or monitoring," said Correale, head of the institute's neuroimmunology and demyelinating diseases department. Mavenclad is designed to target the immune T- and B-cells that trigger relapsing MS without suppressing the entire immune system. With a maximum of 20 days' treatment over two years, the oral drug promotes long-term inhibition of harmful immune cells, reconstituting the immune system. MS is an autoimmune disease, or one in which the immune system attacks normal tissue as well as invadors. Argentine regulators based their approval on the results of five clinical trials. These were the Phase 3 CLARITY, CLARITY EXTENSION, and ORACLE-MS studies, the Phase 2 ONWARD study, and the long-term PREMIERE study. These trials involved more than 2,700 patients with relapsing MS, some of whom researchers followed for more than 10 years. The trials showed that Mavenclad can significantly reduce MS relapse rates, disability progression and brain atrophy. The treatment is recommended for patients who fail to respond adequately, or are unable to tolerate, other therapies. "We are pleased the Argentinian Administration of Medicines, Food and Medical Technology has approved Mavenclad," said Rehan Verjee, the chief marketing and strategy officer of Merck's biopharma business. "Our goal is to ensure fast access to patients who may benefit from this innovative therapy, and we will be working with payers on obtaining reimbursement as a next step."

February 9, 2018 News by Patricia Inacio, PhD

#ACTRIMS2018 – Third Course of Lemtrada Improves Relapse, Disability in MS Patients, CARE-MS II Trial Shows

Multiple sclerosis (MS) patients who experience a relapse after two courses of Lemtrada (alemtuzumab) treatment showed improvements in relapse rate and disability after a third Lemtrada course, according to results of the CARE-MS II trial extension. The poster reporting the findings, titled “Efficacy of Alemtuzumab Retreatment in Patients Who Experienced Disease Activity after…

February 8, 2018 News by Patricia Inacio, PhD

#ACTRIMS2018 – MS Therapy MD1003’s Disability Improvements Hold Over Time, Study Shows

MedDay Pharma’s MD1003 leads to long-lasting improvements in progressive multiple sclerosis patients’ disability, a Phase 3 clinical trial follow-up study shows. Researchers presented the results at the third Annual Americas Committee for Treatment and Research in Multiple Sclerosis Forum in San Diego, Feb. 1-3. The poster presentation was titled “…

January 24, 2018 News by Alice Melão, MSc

Study Identifies MS Patients at Risk of Severe Disease Reactivation After Gilenya Is Discontinued

Multiple sclerosis patients with high relapse rates but less physical impairment before starting on  Novartis’ Gilenya (fingolimod) are likely to experience a surge in disease activity if they stop the treatment, researchers in Turkey report. The study, which dealt with patients with relapsing forms of MS, referred to the surge as "severe disease reactivation," or SDR. Researchers published their article, “Factors Predictive of Severe Multiple Sclerosis Disease Reactivation After Fingolimod Cessation,” in the journal The Neurologist. Studies have shown that Gilenya, which the U.S. Food and Drug Administration approved in 2010, can benefit adults with relapsing MS. It reduces annualized relapse rates and prevents more brain lesions from forming, compared with standard interferon treatments. Lesions are damaged nerve cell areas. Despite its benefits, Gilenya is not recommended for patients with heart or liver problems, low levels of white blood cells, severe herpes virus infections or other infections. Also, patients who do not respond to Gilenya and women who are planning to become pregnant are advised to stop the treatment. Discontinuing Gilenya can lead to a return to pretreatment disease activity, or severe disease reactivation, in some patients. It is unclear why this happens and why it affects only some patients. To better understand what risk factors could be associated with reactivation, a team at Istanbul University compared the demographic and disease features of patients who developed SDR after stopping treatment with Gilenya. SDR was defined as including these elements within 6 months of Gilenya discontinuation: more than 5 gadolinium-enhanced lesions or a tumefactive demyelinating lesion detectable by magnetic resonance imaging, the disease progressing to the point that additional treatment with methylprednisolone or plasma exchange was required, and progressive physical disability reflected by a 1-point or more increase in patients' scores on the Expanded Disability Status Scale, or EDSS, Thirty-one patients at the university’s MS clinic who had discontinued Gilenya were included in the study. Eight experienced SDR and 11 relapses. The mean time for SDR patients' reactivation to occur was 2.6 months, researchers said. Patients had significantly higher levels of lymphocytes — white blood cells involved in autoimmunity — than during Gilenya treatment. When the team compared the disease features of SDR and non-SDR patients, they found that SDR patients had significantly higher annualized relapse rates before starting Gilenya and lower EDSS scores. “A higher ARR [annualized relapse rate] is the major contributory factor toward development of SDR,” the researchers wrote. “Patients who had higher ARRs before fingolimod [Gilenya] treatment must be closely followed up both clinically and radiologically in terms of the early signs of severe reactivation,” they wrote. About 38 percent of the SDR patients failed to respond to steroid treatment. They received a plasma exchange, which led to moderate improvement in their condition. Based on this finding, the researchers suggested that “plasmapheresis [plasma exchange] must be considered in patients exhibiting steroid-refractory SDR.” "In conclusion, SDR may be observed within the first 3 months after cessation of fingolimod," the team wrote. "This may be explained by the rapid influx of lymphocytes into the CNS [central nervous system]. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR."  

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