Effect of Multiple Sclerosis on Daily Activities, Emotional Well-being, and Relationships: The Global vsMS Survey.

BACKGROUND: The vsMS survey was conducted to better understand the negative effects of fatigue, cognitive impairment, emotional burden, and decreased physical functioning on the personal, professional, and social lives of individuals with multiple sclerosis (MS). METHODS: The vsMS survey was an online survey conducted in Australia, Canada, France, Italy, Spain, the United Kingdom, and the United States that assessed the impact of MS on individuals' daily activities, emotional well-being, relationships, and employment. RESULTS: The survey included 1075 participants with relapsing-remitting MS. Almost 42% of participants reported that their ability to perform and manage daily activities had worsened during the previous 2 years. More than 50% reported limitations in daily activities due to fatigue, physical weakness, problems with balance/coordination, heat/cold sensitivity, memory problems, numbness/tingling, trouble concentrating, impaired movement/muscle stiffness, and impaired sleeping. Participants also reported a negative effect on emotional and social factors, including self-esteem, general outlook, well-being, maintaining/starting relationships, ability to progress in their career/keep their job, and ability to cope with life roles. CONCLUSIONS: These data highlight the importance of addressing the impact of MS and the social and emotional disease burdens on daily activities when planning the care of patients with MS.

Nursing Management of Gastrointestinal Adverse Events Associated With Delayed-Release Dimethyl Fumarate: A Global Delphi Approach.

BACKGROUND: Gastrointestinal (GI) adverse events (AEs) are commonly encountered with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing multiple sclerosis (MS). METHODS: Two hundred thirty-nine MS nurses from 7 countries were asked to complete a 2-round Delphi survey developed by a 7-member steering committee. Questions pertained to approaches for mitigating DMF-associated GI AEs. RESULTS: Ninety-six percent of nurses followed the label recommendation for DMF dose titration in round 1, but 77% titrated the DMF dose more slowly than recommended in round 2. Although 86% of nurses advised persons with relapsing forms of MS (PWMS) to take DMF with food, patients were not routinely informed of appropriate types of food to take with DMF. Most nurses recommended both pharmacologic and nonpharmacologic symptomatic therapies for PWMS who experienced GI AEs on DMF. Pharmacologic and nonpharmacologic symptomatic therapies were regarded as equally effective at keeping PWMS on DMF. In round 2, 58% of nurses stated that less than 10% of PWMS who temporarily discontinued DMF went on to permanently discontinue treatment. Sixty-six percent of nurses stated that less than 10% of PWMS permanently discontinued DMF because of GI AEs in the first 6 months of treatment in round 1. Most nurses agreed that patient education on potential DMF-associated GI AEs contributes to adherence. CONCLUSION: This first real-world nurse-focused assessment of approaches to caring for PWMS with DMF-associated GI AEs suggests that, with implementation of slow dose titration, symptomatic therapies, and educational consultations, most PWMS can remain on DMF and, when necessary after temporary discontinuation, successfully restart DMF.

Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: Results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies.

BACKGROUND: Ocrelizumab is an infusible humanized monoclonal antibody that selectively depletes CD20+ B cells. Infusion-related reactions (IRRs) were summarized from the OPERA I, OPERA II, and ORATORIO trials for relapsing and primary progressive multiple sclerosis (MS). METHODS: OPERA I and OPERA II were identical, randomized, double-blind, active-controlled trials that enrolled patients with relapsing MS (RMS). Patients in the ocrelizumab group initially received two 300-mg intravenous (IV) infusions separated by 14 days (on Days 1 and 15); subsequent doses were administered as single 600-mg IV infusions. Ocrelizumab-treated patients also received subcutaneous (SC) placebo injections 3 times weekly. Patients in the active comparator group received SC injections of IFN ß-1a 3 times weekly, as well as placebo infusions on Days 1 and 15 and Weeks 24, 48, and 72. ORATORIO was a randomized, parallel-group, double-blind, placebo-controlled study that enrolled patients with primary progressive MS (PPMS). As in the OPERA studies, patients in the ocrelizumab group initially received two 300-mg infusions separated by 14 days; however, ORATORIO patients continued to receive this divided-dose regimen throughout the study. The ORATORIO control group received IV placebo. Prior to each infusion, all patients in the OPERA and ORATORIO studies were pretreated with 100 mg IV methylprednisolone; additional prophylactic treatment with analgesics, antipyretics, and/or an IV or oral antihistamine was optional. IRRs were defined as adverse events that occurred during or within 24 h of IV infusion of ocrelizumab or placebo. RESULTS: Safety analyses included 1651 patients with RMS from OPERA I and OPERA II (ocrelizumab, n = 825; IFN ß-1a, n = 826) and 725 patients with PPMS from ORATORIO (ocrelizumab, n = 486; placebo, n = 239). Across studies, IRRs were reported in 34.3% (vs 9.7% with IFN ß-1a) and 39.9% (vs 25.5% with placebo) of ocrelizumab-treated patients in the pooled OPERA and ORATORIO populations, respectively. The majority of IRRs were mild to moderate in the OPERA (ocrelizumab, 92.6%; IFN ß-1a, 98.8%) and ORATORIO (ocrelizumab, 96.9%; placebo, 93.4%) studies. IRRs most commonly occurred with the first infusion. Severe IRRs were reported in 2.4% of ocrelizumab-treated patients in the OPERA studies (vs 0.1% with IFN ß-1a) and 1.2% of ocrelizumab-treated patients in ORATORIO (vs 1.7% with placebo). Two serious IRRs occurred across the OPERA studies, both of which occurred with the initial infusion. The first event occurred in an IFN ß-1a-treated patient in association with the initial infusion of IV placebo and consisted of severe balance disorder, dizziness, flushing, and hypoesthesia. The second event was a life-threatening reaction (bronchospasm) that occurred in an ocrelizumab-treated patient 15 min after the infusion started. Frequently reported IRR symptoms included pruritus, rash, throat irritation, and flushing. Premedication use, particularly antihistamines, was associated with fewer IRRs. CONCLUSION: Findings from the OPERA I, OPERA II, and ORATORIO trials show that IRRs were the most frequently reported adverse events with ocrelizumab, were mostly mild to moderate in severity, were reduced with appropriate pretreatment, and decreased with subsequent dosing. IRRs that did occur were effectively managed through infusion rate adjustment and symptomatic treatment.

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

Physical activity and cognitive function in adults with multiple sclerosis: an integrative review.

PURPOSE: To identify and synthesize the research evidence concerning (1) the relationship between physical activity and cognitive performance in persons with multiple sclerosis (MS) and (2) to review the reported effects of physical activity interventions on neurocognitive performance conducted in this population. METHODS: Relevant peer-reviewed journal articles were identified by searching PubMed, PsychINFO, and SPORTDiscus through May 2016. Full-text articles meeting the inclusion criteria were evaluated for quality using tools developed by the National Institutes of Health. Studies deemed to be of poor quality were excluded from the review. RESULTS: Nineteen studies meeting the inclusion/exclusion criteria were analyzed. Nine studies reported significant relationships between higher levels of physical activity or cardiorespiratory fitness and measures of cognitive function. Data extracted from 10 physical activity intervention studies reported mixed results on the effectiveness of physical activity to improve selected domains of cognitive function in persons with MS. CONCLUSION: Although correlational studies provide evidence to support a linkage between physical activity and cognitive function in persons with MS, this linkage is confounded by factors that may have influenced the studies' results. Evidence derived from intervention studies that could support a positive effect of physical activity on cognition in persons with MS is equivocal. Implications for Rehabilitation Physical activity has numerous benefits for persons with multiple sclerosis (MS) including improvements in balance, ambulation, depression, fatigue, and quality of life. Structured physical activity programs may contribute to cognitive function stability or improvement in persons with MS.

Best Practices in Alemtuzumab Administration: Practical Recommendations for Infusion in Patients With Multiple Sclerosis.

With the growing complexity of multiple sclerosis (MS) care, nursing professionals have increasing responsibility in managing clinical disease and treatment. Nursing professionals and other health care providers play important roles in educating patients about disease-modifying therapy options, the course of therapy, and managing potential adverse effects. A panel of nursing and MS experts was convened and used a modified Delphi method to reach consensus on best-practice recommendations for alemtuzumab infusion in MS patients. This valuable clinical resource provides a practical guide for clinicians to optimize patient education and implement strategies for infusion-associated reaction prophylaxis and management when administering alemtuzumab.

Prevention and Management of Infusion-Associated Reactions in the Comparison of Alemtuzumab and Rebif(®) Efficacy in Multiple Sclerosis (CARE-MS) Program.

BACKGROUND: Alemtuzumab is a humanized monoclonal antibody approved in several countries for treatment of relapsing-remitting multiple sclerosis (RRMS). This report summarizes the experience with infusion-associated reactions (IARs) in two phase 3 trials of alemtuzumab in RRMS and examines skilled nursing interventions in IAR prevention and management. METHODS: In the Comparison of Alemtuzumab and Rebif(®) Efficacy in Multiple Sclerosis (CARE-MS) studies, patients with RRMS (treatment naive [CARE-MS I] or with inadequate response [defined as at least one relapse] to previous therapy [CARE-MS II]) received intravenous infusions of alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients were monitored for IARs during and after each infusion. An IAR was defined as any adverse event occurring during any infusion or within 24 hours after infusion. RESULTS: The IARs affected 90.1% of patients receiving alemtuzumab. The most common IARs were headache, rash, pyrexia, nausea, and flushing; most were mild to moderate in severity. Management of IARs consisted of infusion interruption or rate reduction, pharmacologic therapies, and continual patient education and support. Medication administration before and during alemtuzumab infusion reduced IAR severity. Forty-five of 972 alemtuzumab-treated patients (4.6%) required interruption of the first treatment course (ie, infusions did not occur on consecutive days); of these, 24 (53.3%) were still able to complete the first and second full treatment courses. CONCLUSIONS: Nurses played an invaluable role in the detection and management of IARs in the CARE-MS studies. Best practices for management of IARs associated with alemtuzumab include patient and caregiver education, medication to lessen IAR severity, infusion monitoring, and discharge planning.

Effects of functional electrical stimulation on gait function and quality of life for people with multiple sclerosis taking dalfampridine.

BACKGROUND: Multiple sclerosis (MS) can adversely affect gait, causing gait slowing, loss of balance, decreased functional mobility, and gait deficits, such as footdrop. Current treatments for gait dysfunction due to MS are pharmacologic, using dalfampridine, or orthotic, using an ankle-foot orthosis. Functional electrical stimulation (FES) to the fibular nerve stimulates active dorsiflexion and provides an alternative treatment for gait dysfunction caused by footdrop. The objective of this study was to determine the effect of FES on gait function and the impact of MS on walking and quality of life for people with MS taking a stable dalfampridine dose. METHODS: Participants demonstrating gait slowing and footdrop completed the Timed 25-Foot Walk (T25FW) test, 6-Minute Walk (6MW) test, GaitRite Functional Ambulation Profile, 12-item Multiple Sclerosis Walking Scale (MSWS-12), and 36-item Short Form Health Status Survey (SF-36) at screening without FES; the measures were repeated with FES at baseline, 1 month, and 3 months. RESULTS: Twenty participants (8 men and 12 women) completed this unblinded case series study. The mean age, duration of MS, and time taking dalfampridine were 51.7, 15.8, and 1.4 years, respectively. Changes from screening to baseline and screening to 3 months were analyzed. Significant improvement was noted from screening to baseline for the MSWS-12 (P = .024) and SF-36 Physical Function domain (P = .028) and from screening to 3 months for the T25FW (P = .015), MSWS-12 (P = .003), and SF-36 Physical Function (P = .032) and Role Limitation-Physical Health (P = .012) domains. CONCLUSIONS: Improvements above those induced pharmacologically suggest that FES can augment pharmacologic intervention and significantly improve gait function, decrease the impact of MS on walking, and improve quality of life for people with MS.

Efficacy and safety of alemtuzumab in multiple sclerosis and impact on nursing role.

Alemtuzumab, a humanized monoclonal antibody, has shown efficacy for relapsing-remitting multiple sclerosis (MS) in phase 2 and phase 3 trials. Compared with subcutaneous interferon beta-1a, alemtuzumab significantly reduced the risk for accumulation of disability and the rate of relapse, and improved mean disability level from baseline. Notable safety and tolerability concerns include infusion-associated reactions, infections of predominantly mild-to-moderate severity, and autoimmune adverse events, principally thyroid disorders and immune thrombocytopenia. As emerging therapies such as alemtuzumab are approved for the treatment of MS, nurses specializing in the care of MS patients will make increasingly significant contributions to the education of patients, caregivers, and other health-care providers about these therapies' efficacy, tolerability, safety, and administration. This article reviews the phase 2 and phase 3 efficacy and safety results for alemtuzumab, with an emphasis on the role of nurses in communication about this treatment option for those with MS.