Author Archives: Stacy Grieve, PhD

Salt-rich Diet Appears to Trigger Inflammation and Promote Autoimmune Disease by Impact on T-cells, Study Reports

Researchers at Yale uncovered a way that high-salt diets may trigger inflammation and possibly contribute to the development of autoimmune diseases such as multiple sclerosis (MS). Their study, “Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity,” was recently published in the journal Nature…

Low-dose Botox Treatment Improves Urinary Symptoms in MS Patients, Study Finds

Results from a Phase 3 clinical trial show that urinary symptoms can be reduced significantly after treatment with low-dose Botox (100 units) in patients with multiple sclerosis (MS). That finding was reported in the study "Low-dose onabotulinumtoxinA improves urinary symptoms in noncatheterizing patients with MS," published in the journal Neurology.  Most patients with MS develop neurogenic detrusor overactivity (NDO). The detrusor muscles are part of the bladder and are involved in bladder contractions. Because of nerve damage caused by MS, the communication between the spinal cord and the bladder is disrupted and the detrusor muscles become overactive. This results in sporadic and frequent urine leakage. Not surprisingly, NDO can severely affect MS patients' quality of life. Treatments for NDO are usually invasive, and may include surgery and the use of implantable devices. Botox (onabotulinumtoxinA), a minimally invasive option, is approved for the treatment of NDO associated with MS. Studies have shown that injections of Botox (200 units) can reduce urinary incontinence and improve the patient's quality of life. However, high doses of Botox are associated with a potential risk of complications, including urinary retention requiring clean intermittent catheterization (the insertion of a catheter into the bladder to help the person urinate). A previous Phase 3 trial (NCT00910845) testing Botox in patients with idiopathic overactive bladder with urinary incontinence (non-MS patients) showed that Botox at 100 units (half the dose) could reduce urinary incontinence. In 2015, researchers completed a Phase 3 trial (NCT01600716) to assess the safety and effectiveness of Botox (marketed by Allergan) at a dose of 100 units  in noncatheterizing patients with MS and urinary incontinence due to NDO, to determine if the lower dose could reduce urinary symptoms in these patients. The trial included 144 noncatheterized patients with clinically stable MS, and a history of NDO for more than three months.  These patients were recruited from 58 sites across North America and Europe between July 2012 and March 2015. In total, 66 patients received 1 mL injections of Botox (100 units) distributed evenly into the detrusor muscle, while 78 patients received injections of a placebo. Patients were followed for 52 weeks (one year), with check-ups at 2, 6, 12, 24, and 52 weeks. Significant decreases in urinary incontinence episodes in patients treated with Botox were seen as early as two weeks after the injection. This trend continued through week 12. At week six, more patients treated with Botox reported a more than 50% reduction or total reduction in urinary incontinence episodes per day, compared to patients treated with placebo. Botox treatment also increased the maximum cystometric capacity — referring to the volume at which the patient feels he/she can no longer delay urination — compared to placebo, and significantly decreased the pressure in detrusor muscles. Results showed that while symptoms of urinary incontinence decreased, bladder function improved. Regarding incontinence-related quality of life, greater improvements were seen in patients treated with Botox. Importantly, treatment with Botox was long-lasting. Duration of Botox's effect (i.e., median time until  request for another treatment) was 51.7 weeks, compared to only 12.6 weeks in patients treated with placebo. Only 45.5% of patients treated with Botox requested a second dose, while 85.9% of patients treated with placebo requested a second treatment. Botox was generally well-tolerated, and adverse effects for this treatment were low. The most common adverse event reported was urinary tract infection (25.8%). Overall, the team concluded "in noncatheterizing patients with MS and NDO, treatment with onabotulinumtoxinA 100 [units] results in significant and clinically relevant improvements in UI [urinary incontinence] and other urinary symptoms, urodynamics, and QOL [quality of life]...than previously reported with onabotulinumtoxinA 200 U," they wrote. The team also emphasized that "more than half the patients (53%) treated with onabotulinumtoxinA became incontinence free (i.e., “dry”) at week 6 after treatment." Of note, the study was funded by Allergan, and the results are specific to the Botox formulation used. Other botulinum toxin products may not have the same results.

Smoking Increases Relapse Rate in RRMS Patients on Tysabri, Study Suggests

Smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis being treated with Tysabri , an observational study suggests. Multiple sclerosis is a multifactorial disease associated with both genetic and environmental risk factors. Smoking, in particular, has been linked to numerous aspects of MS, including its development and progression. In a previous study, the research team looked at how smoking influences the relapse rate in RRMS patients being treated with interferon beta. From more than 800 patients, they found that smoking one pack per day (about 20 cigarettes) essentially interfered with the positive effect of the IFN-beta treatment and increased the relapse rate by 27%. The researchers then questioned whether the same was true for other treatments. Tysabri, developed by Biogen, is a monoclonal antibody that targets the alpha-4 integrin protein. By interfering with this molecule, the therapy prevents white blood cells from moving into the central nervous system, suppressing the immune reaction that contributes to MS symptoms. In the study, 355 Tysabri-treated RRMS patients from the Danish Multiple Sclerosis Centre were assessed. To gather information on smoking habits and body mass index, the patients filled out a 100-question survey. Data was collected between the start of the treatment and a two-year follow-up visit. Results showed that smoking one pack of cigarettes per day increases the relapse rate by 38% in RRMS patients on Tysabri. This increase in relapse rate takes into account both sex and age at the start of treatment, since age can affect the relapse rate. For example, an increase in age by one year raises the number of relapses by 2%. The researchers also looked at the relationship between smoking and the presence of two immune-related alleles: HLA-DRB1*15:01 and HLA-A*02:01. Previous studies showed that HLADRB1*15:01 is associated with an increased risk of developing MS, while HLA-A*02:01 is linked to a decreased risk. Although previous studies reported a link between smoking and these two alleles in MS patients, the current study did not find an association between smoking and carrying either of these alleles. Based on the results, the researchers concluded that smoking significantly increases the relapse rate in RRMS patients receiving Tysabri. According to the team, the results "add important information that hopefully will sharpen the focus on the overall harmful effects of smoking in MS patients."

Falls Common Among Wheelchair, Scooter Users in People with MS, Study Reports

The majority of people living with multiple sclerosis who use wheelchairs or scooters for mobility reported falling at least once over a six-month period, according to a new study. While most studies have focused on ambulatory MS patients, this may be the first study to assess the prevalence and circumstances of falls among those who already experience significant mobility issues and require the use of wheelchairs or scooters to get around. In ambulatory MS patients who are able to move around on their own, about 50 percent reported falling during a six-month period. The current study recruited 44 MS patients from May 2014 to July 2015 who required wheelchairs or scooters to move about. These patients were from medical centers across the United States and Asia. They were asked to complete a survey focusing on the prevalence of falls, the frequency of injuries, the circumstances surrounding the falls, and quality-of-life indicators. Thirty-three of the 44 participants (75 percent) reported falling at least once in the previous six months. This number is higher than any of the other studies that assessed the prevalence of falls in MS patients. Many of these people experienced more than one fall within those six months. Of these falls, 87.5 percent occurred inside the home. The top four activities reported by participants that led to these falls included using the toilet, transferring, walking short distances, and reaching for an object. Some of the people said the falls were serious, and 8 percent of participants reported an injury because of their fall. Perhaps for this reason, many reported concerns about falling (76.7 percent). And, more telling, 65.9 percent of these MS patients reported altering their activities because they feared falling. The use of mobility devices may affect the prevalence of falls. Participants were asked if they had fallen using a specific mobility device. Here is how they responded: 66.7% reported falling while using power wheelchairs; 37.5% fell while using manual wheelchairs; 66.7% fell when using scooters; 71.4% reported falling while using a walker; 100% fell while using a cane. Because of the high prevalence of falls while using a mobility device, researchers said, clinicians should provide better education regarding the use and function of these mobility devices. There were no significant correlations between people who experienced falls and quality-of-life indicators in this study. Results from the study highlight the need for interventions specifically targeted for MS patients who use mobility devices such as wheelchairs and scooters. The body of research regarding predictors of falls suggest that some of the risk factors can be modified; therefore, more effort should be made to prevent falls using targeted rehabilitation interventions.

Long-term Use of Ampyra Lowers Medical Costs, Hospital Visits for MS Patients, Study Finds

A recent study has found that continued use of Ampyra (dalfampridine extended-release, sold in the U.S. by Acorda Therapeutics) by patients with multiple sclerosis (MS) lowers both inpatient hospital visits and overall healthcare costs. Results from the study, titled “Inpatient Admissions and Costs Associated with Persistent Use of Dalfampridine Extended-Release in Multiple Sclerosis: A Claims Database Analysis,” were published in the Journal of Managed Care and Specialty Pharmacy. For many patients with MS, impaired walking causes a significant concern. A Phase 3 trial (NCT00127530) from a decade ago showed that Ampyra could improve walking in patients with MS over a 14-week observational period. Improved walking was demonstrated by an increase in the speed of walking. The current study assessed how the long-term use of Ampyra influences inpatient admissions and costs associated with hospital visits using MS patient cohorts. Data was collected from the Truven Health Analytics MarketScan Commercial Claims and Encounters (CCAE) Database. This database includes information on medical benefits and health insurance claims. Persistent Ampyra users were found to be less likely to be admitted to the hospital for any cause compared to patients who were non-persistent Ampyra users. Similarly, costs associated with inpatient care were also significantly lower for patients with long-term Ampyra use, with a difference of $846 between the two groups. Importantly, persistent-use Ampyra patients who were hospitalized were less likely to require extensive medical resources during their inpatient stay. Based on the results, the team concluded that persistent use of Ampyra by patients with MS lessens hospital admissions and lowers the use of resources and costs.

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