Author Archives: Janet Stewart, MSc

Consecutive Use of Gilenya and Lemtrada Causes Disease Activity in MS Patient, Case Report Suggests

Multiple sclerosis (MS) patients may experience severe disease exacerbation after switching from Novartis’ Gilenya (fingolimod) to Sanofi Genzyme’s Lemtrada (alemtuzumab), a case report suggests. This unexpected high disease activity raises questions about managing MS through the consecutive use of immunotherapies. The case report, “Unexpected high multiple…

Complications from Gilenya Treatment Managed Successfully, Case Report Says

A case study reported the successful management of a multiple sclerosis (MS) patient who developed a rare condition in the brain — progressive multifocal leukoencephalopathy (PML) — due to treatment with Novartis Pharmaceutical’s Gilenya (fingolimod). The study, titled “Fingolimod-associated PML with mild IRIS in MS: A clinicopathologic study,” was published in the journal Neurology Neuroimmunology & Neuroinflammation. The patient was a 34-year-old woman whose MS was diagnosed at age 14. She had been treated with interferon-beta 1b for 11 years and experienced 12 MS relapses during that period. Interferon treatment was discontinued. For the past four years she had been taking Gilenya without experiencing any relapses and no signs of disease worsening. The woman visited the clinic because she noticed muscle weakness in her right hand, dysarthria (which involves slurred or slow speech), and hemiparetic gait (abnormal gait caused by weakness in the muscles on one side of the body). Gilenya treatment was discontinued because the patient had low numbers of white blood cells in her circulation. One month later, she was admitted to the hospital. Aphasia (impairment of language, affecting the production or comprehension of speech and the ability to read or write) and right hemiplegia (paralysis of one side of the body) worsened during the first month of hospitalization. A very low level of JC virus was detected in the patient's cerebrospinal fluid, which bathes the brain and the spinal cord. Infection with JC virus can cause PML, with symptoms including mental deterioration, vision loss, speech disturbances, ataxia (inability to coordinate movements), paralysis, and coma. A biopsy of her brain tissue showed there were signs of JC virus infection and a mild immune response to it, suggesting a diagnosis of PML-immune reconstitution inflammatory syndrome (PML-IRIS). IRIS is an exacerbated inflammatory response that aggravates the damage caused by JC virus infection. The patient was treated with 1 gram of methylprednisolone (intravenously) daily for three days, and weekly oral mefloquine. Two months later, no JC virus could be detected in her cerebrospinal fluid, and her white blood cell counts returned to normal. Aphasia and right hemiplegia gradually improved. The researchers emphasized there have only been a total of 13 cases of PML reported in Gilenya-treated patients with relapsing-remitting MS to date, including this single case of PML-IRIS. The team highlights that Gilenya-associated PML in MS may be accompanied with IRIS, but that it may be difficult to detect because the symptoms are relatively mild,  causing underestimation. "The clinical and pathologic diagnosis of PML-IRIS is challenging, particularly when the consequence of JCV reactivation and immune reconstitution is not clear," the researchers wrote. "The pathologic features in fingolimod-associated PML in MS may include only early and weak characteristic features with immunoreaction, differing from previously reported PML by other disease-modifying treatments (DMTs)."

Health Costs Higher, But Outcomes Better for MS Patients Who Take Their Meds, Study Finds

Multiple sclerosis patients who adhere strictly to their medication pay more but stay healthier in the long run than those who don't, a study found. Researchers at Liberty University College of Osteopathic Medicine in Lynchburg, Virginia, analyzed data from 2004 to 2013, including electronic health records, insurance claims and self-reported medication adherence. They based their assessment of health outcomes on inpatient admission, emergency room visits, outpatient appointments  and healthcare costs. In total, 681 participants answered questionnaires about medication adherence and disease outcomes, including the Multiple Sclerosis Impact Scale and the Kurtzke Expanded Disability Status Scale. Also used was the Treatment Satisfaction Questionnaire for Medication to assess satisfaction with the medication taken. Patients who took their medicines most rigorously reported 14 percent less severe physical impact of MS, and 17 percent less severe psychological impact than those with low adherence. These patients also reported a 12 percent decrease in disability level, and believed their treatment plan was 7 percent more effective. However, the total overall costs were higher for patients who adhered to their doctor's orders. The researchers said it's more difficult to detect improvements in health outcomes for MS than for other chronic illnesses. This is partly because the only test for changes in disease status is brain imaging, which is expensive and not done routinely. Furthermore, brain imaging only detects new lesions following a relapse, which cannot be compared to previous or future imaging in a quantifiable way. In fact, no simple tests exist for measuring disease severity in MS as there are in other chronic diseases, making it difficult to determine whether treatment benefits justify their cost.

RedHill Awaits US Patent for Antibiotic Combo, RHB-104, as Potential RRMS Therapy

RedHill Biopharma has received a Notice of Allowance for a new patent on RHB-104 its potential therapy for patients with relapsing-remitting multiple sclerosis (RRMS). Once granted by the United States Patent and Trademark Office (USPTO), this patent will be valid until 2032. RHB-104 is a proprietary, orally-administered antibiotic combination with potentially potent intracellular, antimycobacterial…

Myelin-producing Brain Cells Regenerated Using Stem Cells in Early Study

Researchers, using two different kinds of stem cells in rats, were able to regenerate oligodendrocytes — myelin-producing brain cells that are defective in multiple sclerosis (MS). They were also able to grow adult neural stem cells in laboratory cultures and prod them to develop into oligodendrocytes. The exact cause of MS is unknown — including what triggers attacks on myelin — but the loss of oligodendrocytes seen in the disease is known to play a role in its progression. Nerve cells in the brain send their signals through their axons, long arm-like structures that extend out from the centers of the nerve cells. The signals are electrical pulses transmitted along the length of an axon. Oligodendrocytes provide the insulation — called myelin — that wraps around axons, speeding up the transmission of electrical signals through the nerve cells. Loss or malfunction of oligodendrocytes means that signaling in the brain is impaired. It is this slowing of signaling that is thought to cause MS symptoms. Researchers from the Heinrich-Heine-University, Germany, with support from British and Chilean colleagues, designed a novel approach to regenerate oligodendrocytes, according to a press release. Stem cells are immature cells that give rise to differentiated cells — cells with a specific function, such as oligodendrocytes. Adult neural stem cells can divide and produce nerve cells and other brain cells, including oligodendrocytes. However, in normal circumstances, the regeneration of cells that take place in the human brain is not enough to repair the damage seen in MS. The researchers set out to find conditions that would promote the differentiation of adult human NSCs into oligodendrocytes. They discovered that another type of stem cell, mesenchymal stem cells (MSCs), could provide the signals required. First they tested their system in rats, and found that by using factors produced by human MSCs, they could induce the growth of new oligodendrocytes in the animals. Then they grew adult NSCs in the laboratory, and using the same factors from human MSCs were able to promote the establishment of oligodendrocytes in the cultured cells.

Most Patients Prefer Betaconnect Autoinjector for MS Treatment, German Survey Shows

A patient satisfaction evaluation of three autoinjector devices for delivering multiple sclerosis treatments found that Bayer's electronic autoinjector Betaconnect was the choice of 57 percent of the 85 people who took part in the study. Higher satisfaction with an autoinjector can lead to better adherence, or patients sticking with treatment, according to the study's authors. Adherence means remaining on a medication and following the prescribed procedure for taking it. An independent market research company organized the survey and conducted face-to-face interviews in five German cities. Autoinjectors are devices that allow patients to inject themselves with their own medication. People with MS use them to deliver beta interferon-based therapies. The devices often provide features to improve patient comfort and adherence. These include reminder functions, because people often forget to take a self-administered drug. Other features include the ability to adjust injection speed and depth; signaling at the beginning and end of the injection process; the ability to correct the positioning of the device on the skin; and a display to visualize injection progress. The 85 participants in the study were using one of three autoinjectors. Two were electronic autoinjectors, Bayer's Betaconnect and EMD Serono's Rebismart, and one was mechanical: Novartis' autoinjector ExtaviPro. Eighty-two percent of those using Betaconnect devices expressed satisfaction. The figures were 67 percent for the Rebismart, and 60 percent for the ExtaviPro. Assuming the medication they were taking could be administered with any of the three devices, the participants were asked which one they preferred. The Betaconnect autoinjector was preferred by 57 percent of participants and the RebiSmart by 37 percent. Five percent liked the ExtaviPro the best.

Costs Associated with Multiple Sclerosis Rise as Severity of Disease Increases, European Study Shows

Costs associated with multiple sclerosis increase as the disease worsens, according to a study of more than 16,000 patients in 16 European countries. The study, “New insights into the burden and costs of multiple sclerosis in Europe,” was published in the Multiple Sclerosis Journal. Researchers obtained their information from patient self-reporting. Patients used the Kurtzke's Expanded Disability Status Scale (EDSS) to assess the severity of their disease. They also reported on their quality of life and their resource use. Patients were divided into three categories. Those with a score between 0 and 3 on the EDSS scale were deemed to have a mild disease. The disease of those with scores of 4 to 6.5 was considered moderate. And the disease of those with scores of 7 to 9 was classified as severe. Patients assessed their health-related quality of life with the EuroQol Five Dimensions questionnaire. The average age of the 16,808 participants was 51 and a half years old. The work capacity of MS patients dropped from 82 percent of a healthy person's to 8 percent as the severity of the disease increased, researchers said. Patients' quality of life scores were about the same as those seen in the general population when they had a mild disease. But they plunged to less than zero when their disease became severe. The mean annual cost of having a mild form of MS was 22,800 euros, or around $26,300, researchers reported. The cost of having a moderate disease was 37,100 euros, or about $42,800. And the cost of a severe disease was 57,500 euros, or $66,340. Healthcare accounted for 68 percent of total costs with a mild disease, 47 percent with a moderate disease, and 26 percent for a severe disease. "Costs are dependent on the availability, use and price of services and on disease severity," the researchers wrote. "Costs were related to disease severity" in all countries "and were dominated by production losses, non-healthcare costs and DMTs," or disease-modifying therapies. Those therapies may be a key reason why the highest percentage of healthcare costs occurred in patients with a mild disease, researchers said. Doctors prescribe a lot of DMTs to this group. Other factors related to the high percentage were that many patients with mild diseases are still able to work -- meaning they incur fewer production-loss costs -- and this group requires fewer community services. As MS becomes more severe, patients' production losses rise, and they use more community services. "The intensity of healthcare service use varied widely across the countries," researchers wrote. "This reflects differences in healthcare organization, medical traditions, ease of access and – most importantly – availability of given services." Researchers also assessed patients' levels of fatigue and cognitive difficulties. Ninety-five percent reported fatigue, and 71 percent cognitive difficulties. Fatigue and cognitive difficulties had significant impacts on quality of life scores, researchers said.

Combined High-Intensity Interval, Resistance Training Improves Physical Health and Quality of Life in MS

In a pilot study with patients with multiple sclerosis, high-intensity interval training combined with resistance training improved physical capacity and quality of life in a pilot study of multiple sclerosis (MS) patients — whether or not they were disabled. French researchers at the University of Strasbourg assessed physical capacity, strength and quality of life before the training started, and then again after completing a 12-week exercise program. They divided participants into two groups: one of 18 patients with no disabilities, and a group of eight with disabilities. Participants followed a personalized exercise program involving both high-intensity interval training — a kind of cardiovascular exercise strategy alternating short periods of intense anaerobic exercise with less intense recovery periods — and resistance training to improve muscular strength and endurance. Scientists used a French version of the Multiple Sclerosis Quality Of Life-54 test — a questionnaire filled out by MS patients to measure health-related quality of life — with five additional questions. After the exercise program, women improved significantly in vitality, general well-being and physical health composite scores in the quality of life assessment, while men showed no significant improvements. Vitality and general well-being only improved in the group with no disability. Peak oxygen consumption improved by 13.5 percent, and maximum tolerated power — a measure of maximum energy that can be expended — by 9.4 percent. Muscle strength increased in both quadriceps and hamstrings. Women showed better improvements than men in peak oxygen consumption, maximal tolerated power, strength in both quadriceps and hamstrings, and quality of life. Both groups showed increased peak oxygen consumption and strength. “Our study has shown that high-intensity interval training combined with resistance exercise training induced an improvement in physical capacity and quality of life. Moreover, this study allowed patients, irrespective of their sex or EDSS [Expanded Disability Status Scale] score, to resume exercise autonomously,” the team wrote. "High-intensity interval training is well tolerated too and can be used in clinical rehabilitation with resistance training, in both men and women with and without disabilities."

Allergy Medicine Fails to Reduce Flu-Like Syndrome in Relapsing-remitting MS Patients, Study Shows

According to a new clinical trial, the allergy treatment cetirizine fails to alleviate a flu-like condition that interferon-beta treatment generates in people with relapsing-remitting multiple sclerosis. The results, which surprised researchers, apply to flu-like syndrome, or FLS. Cetirizine is an over-the-counter medicine sold under the brand names Zirtec, Zyrtec, Reactine, and Triz. FLS affects roughly 75 percent of patients who take interferon-beta, also known as IFN-beta. It can cause fever, chills, muscle pain, weakness, and headache. The symptoms commonly occur three to six hours after an IFN-beta injection and last up to 24 hours. Although FLS usually subsides in the first three months of IFN-beta therapy, it persists in some patients, causing them to miss doses or even discontinue the treatment. Cetirizine is an antihistamine for hay fever and allergies. The purpose of the clinical trial was to determine whether cetirizine could alleviate RRMS patients' FLS. In order to determine study results, patients did self-assessments of how much discomfort their FLS caused them. There were no significant changes in the two groups' average self-assessment scores at four and eights weeks of treatment, suggesting that cetirizine does not offer significant benefits to RRMS patients with FLS. “The addition of a [cetirizine] to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to improve symptoms significantly compared with placebo," the team wrote. "FLS continues to be inadequately treated in many RRMS patients. Further investigations are needed to elucidate the underlying mechanisms of IFNβ-induced FLS and develop adequate strategies for prevention and treatment."

Lipoic Acid, an Over-the-counter Antioxidant, Seen to Slow Brain Atrophy in SPMS Patients

The over-the-counter antioxidant lipoic acid slowed brain deterioration in patients with secondary progressive multiple sclerosis (SPMS), according to a pilot study. An Oregon Health & Science University research team conducted the study, "Lipoic acid in secondary progressive MS." It was published in the journal Neuroimmunology and Neuroinflammation. A hallmark of SPMS is increasing disability. This form of the disease follows a less severe form known as relapsing-remitting MS (RRMS). There are few treatment options for SPMS. The body produces lipoic acid, also known as oalpha lipoic acid, to help break down nutrients to generate energy. Companies also manufacture the antioxidant as a dietary supplement or drug. It is sold over-the-counter in a number of countries. Oregon researchers' two-year, randomized, double-blind study covered 51 patients with SPMS. Twenty-seven of the participants received a daily dose of 1,200 milligrams of lipoic acid, while 24 received a placebo. Those who took lipoic acid had 68 percent less brain deterioration than those who took a placebo, researchers said. The team used magnetic resonance imaging, or MRI, to measure brain tissue loss. Researchers also noticed longer walking times and fewer falls in the lipoic acid group. They hope to confirm the findings in a larger, multicenter clinical trial to begin later this year. Lipoic acid was safe and well-tolerated at the dose used, with the most common side effect being upset stomach, the research team said. “These are high doses,” Dr. Rebecca Spain, assistant professor of neurology at the medical school and the study's lead author, said in a press release. “And while it seems safe, we won’t know whether it actually improves the lives of people with MS until we can replicate the results in the pilot study through a much bigger clinical trial. Fortunately, we’re going to be able to answer that question with the participation of kind volunteers.”

Tecfidera Improves MS Patients’ Work Productivity, Compared with Other Therapies, Study Shows

Multiple sclerosis patients taking Tecfidera, or dimethyl fumarate, were more productive at work than those on Copaxone or beta-interferon therapies, according to a study. Tecfidera also increased patients’ quality of life, researchers said. The study covered patients with relapsing-remitting multiple sclerosis, or RRMS. The four beta-interferon treatments were Avonex, Betaseron, Rebif,…


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