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Highlights • Infusion-related reaction rates were similar in shorter and conventional infusions • The majority of infusion-related reactions were mild to moderate • No infusion-related reactions were serious, life-threatening or fatal • No new safety signals were observed with a shorter infusion time • Shortening the infusion time may lessen the burden on patients and site staff, Background: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). Shortening the 600 mg infusion to 2 hours reduces the total site stay from 5.5–6 hours (approved infusion duration including mandatory pre-medication and post-infusion observation) to 4 hours. The safety profile of shorter-duration ocrelizumab infusions was investigated using results from ENSEMBLE PLUS. Methods: ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early-stage relapsing-remitting MS received ocrelizumab 600 mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, ocrelizumab 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration); the durations of the initial infusions (2×300 mg, 14 days apart) were unaffected. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first Randomized Dose. Results: From November 1, 2018, to December 13, 2019, 745 patients were randomized 1:1 to the conventional or shorter infusion group. At the first Randomized Dose, 99/373 patients (26.5%) in the conventional and 107/372 patients (28.8%) in the shorter infusion group experienced IRRs. The majority of IRRs were mild or moderate; >99% of all IRRs resolved without sequelae in both groups (conventional infusion group, 99/99; shorter infusion group, 106/107). No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuations occurred. During the first Randomized Dose, 22/373 (5.9%) and 39/372 (10.5%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption. Adverse events were consistent with the known safety profile of ocrelizumab. Conclusion: The rates and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shortening the infusion time to 2 hours reduces the total site stay time (including mandatory pre-medication/infusion/observation) from 5.5–6 hours to 4 hours, and may reduce patient and site staff burden.

Background: Appropriate counseling and treatment for women with multiple sclerosis (MS) who may become pregnant requires an understanding of the effects of exposure to disease-modifying therapies (DMTs) during pregnancy. Current reports and studies are limited in their usefulness, mostly by small sample size. Branded glatiramer acetate (GA) is a DMT approved for the treatment of relapsing forms of MS. For more than 2 decades, it has been shown to be efficacious and to have a favorable safety profile. The Teva Pharmaceutical Industries Ltd global pharmacovigilance database comprises data from more than 7000 pregnancies, during which women with MS were exposed to treatment with branded GA. Methods: We analyzed data from Teva's global pharmacovigilance database. Pregnancy outcomes for patients treated with branded GA were compared with reference rates of abnormal pregnancy outcomes reported in two large registries representing the general population. Results: Pregnancies exposed to branded GA were not at higher risk for congenital anomalies than what is expected in the general population. Conclusions: These data provide evidence that branded GA exposure during pregnancy seems safe, without teratogenic effect.

Introduction Multiple sclerosis (MS) typically requires life-long management with disease-modifying therapies (DMTs). Many DMTs require regular self-injection, and can be associated with injection site reactions, pain, and needle/injection phobia—but these can be addressed by improvements in autoinjector design. The aim of this study was to investigate patient satisfaction and preference for BETACONNECT™ (Bayer Pharma AG), a novel interferon beta-1b autoinjector. Methods Patients in Germany performing self-injections using BETACONNECT took part in the study. Data were collected through an online 15-min structured survey. Participants rated their experience with BETACONNECT on a 6-point scale and those satisfied with BETACONNECT were asked to describe the reason using a free-text box. Results One-hundred and eighteen patients with MS completed the survey. Ninety percent preferred BETACONNECT to their previous injection method (only 4% previously used manual injections, so most had previously used other autoinjectors). Ninety-two percent were very confident/confident in their ability to perform an injection using BETACONNECT. The most common free-text responses to “Why are you satisfied with the BETACONNECT™ autoinjector?” were ease of use (46%), less irritation/pain at the injection site (33%), and smoother injections (24%). Features considered most useful were automated injections (98%), adjustable injection speed (98%), and adjustable injection depth (98%). Ninety-seven percent thought it was easy to know when an injection was complete and 95% agreed/strongly agreed it was easy to learn to use the autoinjector. Seventy-three percent agreed that the quietness and effortlessness of the BETACONNECT reduced their level of injection anxiety, 92% that its size and shape makes it easy to handle during injections, and 67% that it decreases injection site pain. Eighty percent of those using the reminder function thought they were less likely to miss an injection. Conclusion Patients with MS self-injecting interferon beta-1b expressed a high level of satisfaction and preference for BETACONNECT. Thus, BETACONNECT represents a valid option to improve patients’ overall injection experience. Funding Bayer HealthCare Pharmaceuticals. Electronic supplementary material The online version of this article (doi:10.1007/s40120-015-0036-y) contains supplementary material, which is available to authorized users.

Background: Adherence to medical interventions is a global problem. With an increasing amount of partially effective but expensive drug treatments adherence is increasingly relevant in multiple sclerosis (MS). Perceived lack of efficacy and side effects as well as neuropsychiatric factors such as forgetfulness, fatigue and depression are major determinants. However, research on adherence to behavioural interventions as part of rehabilitative interventions has only rarely been studied. Methods: In a one-day meeting health researchers as well as patient representatives and other stakeholders discussed adherence issues in MS and developed a general draft research agenda within a focus group session. Results: The focus group addressed four major areas: (1) focussing patients and their informal team; (2) studying health care professionals; (3) comparing practice across cultures; and (4) studying new adherence interventions. Conclusions: A focus on patient preferences as well as a non-judgemental discussion on adherence issues with patients should be at the core of adherence work.

Bladder symptoms such as urinary urgency, frequency, and incontinence are common in people with multiple sclerosis (MS). These symptoms, which often result from neurogenic detrusor overactivity (NDO), can have a major impact on patients' day-to-day lives. However, in many cases they are over-looked in the clinical management of MS. The objective of this study was to develop and validate a reliable, sensitive, and specific screening tool for patients with bladder problems related to MS. We performed a literature review and then conducted a content validation study followed by a multisite observational study of a new screening tool, the Actionable Bladder Symptom Screening Tool (ABSST). All ABSST domains as well as the total score met the threshold for good internal consistency (Cronbach α ≥ 0.70), with a Cronbach α value of 0.95 for the total score and values ranging from 0.85 to 0.90 for the three domains. The validity of the ABSST was demonstrated by high correlation of the domains and total score with the Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity and Total Health-Related Quality of Life (HRQOL) scores (Spearman correlation coefficient ≥ 0.782). The predictive validity of the ABSST total score to identify patients who might receive a recommendation to see a urologist was strong. This new instrument, which was developed with input from clinicians as well as MS patients, meets the current content validity and psychometric testing thresholds established by the US Food and Drug Administration, with high sensitivity and specificity.

There are currently no assessment tools that focus on evaluating patients with multiple sclerosis (MS) who are experiencing a relapse or that evaluate patients' response to acute relapse treatment. In practice, assessments are often subjective, potentially resulting in overlooked symptoms, unaddressed patient concerns, unnoticed or underrecognized side effects of therapies (both disease modifying and symptomatic), and suboptimal therapeutic response. Systematic evaluation of specific symptoms and potential side effects can minimize the likelihood of overlooking important information. However, given the number of potential symptoms and adverse events that patients may experience, an exhaustive evaluation can be time-consuming. Clinicians are thus challenged to balance thoroughness with brevity. A need exists for a brief but comprehensive objective assessment tool that can be used in practice to 1) help clinicians assess patients when they present with symptoms of a relapse, and 2) evaluate outcomes of acute management. A working group of expert nurses convened to discuss recognition and management of relapses. In this article, we review data related to recognition and management of relapses, discuss practical challenges, and describe the development of an assessment questionnaire that evaluates relapse symptoms, the impact of symptoms on the patient, and the effectiveness and tolerability of acute treatment. The questionnaire is designed to be appropriate for use in MS specialty clinics, general neurology practices, or other practice settings and can be administered by nurses, physicians, other clinicians, or patients (self-evaluation). The relapse assessment questionnaire is currently being piloted in a number of practice settings.

The management paradigm for multiple sclerosis (MS) is moving toward earlier diagnosis (on the basis of clinical, paraclinical, and laboratory findings), differentiation of patients with varying prognoses, and earlier implementation of treatment in selected individuals. On the basis of a survey conducted at the American Association of Neuroscience Nurses Annual Conference in 2009, several topics were identified for which nurses indicated a need for new and updated information, including current diagnostic methods for MS, optimal time to initiate treatment of MS, and emerging therapies for MS. This article was designed to address these issues.

Several recent studies have shown that mobility loss and walking impairment are significant concerns among people living with multiple sclerosis (MS). Ongoing challenges related to the assessment and management of mobility loss can have a direct impact on outcomes and patient quality of life. These challenges are evident across the spectrum of patient experience and at all stages on the treatment continuum. In June 2009 a panel of MS experts met to review current standards of care in the treatment of mobility loss in MS. The objective of the roundtable meeting was to identify specific actions that patients, care partners, and health-care professionals should consider to improve the assessment, diagnosis, and treatment of mobility loss and walking impairment in people with MS. The meeting was hosted by the International Organization of Multiple Sclerosis Nurses and was supported by a grant from Acorda Therapeutics.

Disease-modifying drugs (DMDs) have transformed the treatment of relapsing-remitting multiple sclerosis (RRMS). Several studies have shown the benefits of long-term treatment in RRMS; however, all multiple sclerosis (MS) therapies are associated with treatment-related tolerability and safety issues that may challenge patient compliance with therapy. Tolerability issues include flulike symptoms and injection-site reactions for interferon β(IFNβ) and lipoatrophy and systemic postinjection reactions for glatiramer acetate (GA). Altered blood cell counts, depression, and elevated liver enzymes, including rare cases of acute liver injury, are safety issues that have been associated with IFNβand, rarely, systemic anaphylactoid reactions with glatiramer acetate. Common tolerability issues associated with natalizumab are hypersensitivity and postinfusion reactions, and mitoxantrone may cause amenorrhea, nausea, and alopecia. Serious safety issues that have limited the use of natalizumab and mitoxantrone as first-line treatments are progressive multifocal leukoencephalopathy for natalizumab and cardiotoxicity and leukemia for mitoxantrone. Although both tolerability and safety issues can affect patient adherence to therapy, numerous strategies are available to manage tolerability and monitor safety issues. Through careful monitoring of treatment-related safety issues, patient education, and tolerability management strategies, treatment nonadherence can be minimized, thereby maximizing the treatment benefits of DMDs.

Cognitive impairment is a common problem in multiple sclerosis (MS); up to 65% of patients exhibit some neuropsychological dysfunction during the course of their disease. It is a major contributing factor to unemployment, accidents, impairment of daily functioning, and loss of social activity in those affected by MS. The areas of cognition typically impaired are memory, attention, information processing, executive functions, and visuospatial skills. Cognitive dysfunction is independent of disease duration and level of disability; cognitive decline may begin in the earliest stages of MS before patients become even mildly disabled. Structural brain imaging studies show a positive correlation between the extent of brain atrophy and cognitive dysfunction. Despite its prevalence in MS, cognitive dysfunction often goes undiagnosed or is misdiagnosed as depression, stress, stubbornness, lack of intelligence, or psychosis. Because nurses play such an important role in the care of patients with MS, they are in a position to identify patients with cognitive dysfunction, educate patients and their families on ways to cope with cognitive deficits, and counsel patients on available treatment options. Practical guidelines help nurses identify and care for cognitively impaired MS patients.

Providing optimal patient care in multiple sclerosis (MS) is dependent on both the patient and the healthcare system. One of the greatest challenges to optimal patient care is ensuring patient adherence to treatment. The two reasons given most often for treatment discontinuation are adverse effects and lack of efficacy. Adverse effects can be anticipated and managed, in part through well-established protocols, but also through industry-sponsored nursing support programs. These strategies can reduce needless discontinuations when patients experience common adverse effects. Lack of efficacy can be addressed for many patients by providing them with enough education to develop reasonable expectations for treatment and long-term prognosis. As important as early and continuous treatment are, these strategies are essential for providing optimal patient care in MS.

Patients with multiple sclerosis (MS), a disease of the central nervous system that disrupts signals within the brain and also the signals between the brain and body, will likely experience symptoms that may negatively impact their quality of life (QOL). Due to the complexity of MS and its disease burden, multidisciplinary management that combines pharmacologic and nonpharmacologic strategies with patient education is necessary. Diagnosing relapses of MS in clinical practice can be difficult due to the multiple subtypes of MS, variations of symptomatology, and pseudo-relapses. Managing relapses also presents its own set of challenges, for example, evaluating if treatment is appropriate and determining which agent would be most effective for a patient if treatment is recommended. Patient education is essential for achieving optimal outcomes for patients with MS and improving patient QOL, and should increase awareness of: (1) the disease itself and its progression; (2) the signs and symptoms of MS; (3) current treatment strategies and plan of care; (4) the recognition and management of relapses; (5) the value of treatment adherence and impact of nonadherence; and (6) hope for the future. The management of active MS may be further complicated by the complex variety of pharmacotherapeutic options, and in some instances, by having to switch between agents and drug classes. Newer agents in development (eg, alemtuzumab, ocrelizumab, laquinimod) offer the opportunity to expand the therapeutic armamentarium, although further long-term data are required to evaluate any safety concerns associated with newer agents.

There are currently no assessment tools that focus on evaluating patients with multiple sclerosis (MS) who are experiencing a relapse or that evaluate patients' response to acute relapse treatment. In practice, assessments are often subjective, potentially resulting in overlooked symptoms, unaddressed patient concerns, unnoticed or underrecognized side effects of therapies (both disease modifying and symptomatic), and suboptimal therapeutic response. Systematic evaluation of specific symptoms and potential side effects can minimize the likelihood of overlooking important information. However, given the number of potential symptoms and adverse events that patients may experience, an exhaustive evaluation can be time-consuming. Clinicians are thus challenged to balance thoroughness with brevity. A need exists for a brief but comprehensive objective assessment tool that can be used in practice to 1) help clinicians assess patients when they present with symptoms of a relapse, and 2) evaluate outcomes of acute management. A working group of expert nurses convened to discuss recognition and management of relapses. In this article, we review data related to recognition and management of relapses, discuss practical challenges, and describe the development of an assessment questionnaire that evaluates relapse symptoms, the impact of symptoms on the patient, and the effectiveness and tolerability of acute treatment. The questionnaire is designed to be appropriate for use in MS specialty clinics, general neurology practices, or other practice settings and can be administered by nurses, physicians, other clinicians, or patients (self-evaluation). The relapse assessment questionnaire is currently being piloted in a number of practice settings.

There is need for a brief but comprehensive objective assessment tool to help clinicians evaluate relapse symptoms in patients with multiple sclerosis (MS) and their impact on daily functioning, as well as response to treatment. The 2-part Assessing Relapse in Multiple Sclerosis (ARMS) questionnaire was developed to achieve these aims. Part 1 consists of 7 questions that evaluate relapse symptoms, impact on activities of daily living (ADL), overall functioning, and response to treatment for previous relapses. Part 2 consists of 7 questions that evaluate treatment response in terms of symptom relief, functioning, and tolerability. The ARMS questionnaire has been evaluated in 103 patients with MS. The most commonly reported relapse symptoms were numbness/tingling (67%), fatigue (58%), and leg/foot weakness (55%). Over half of patients reported that ADL or overall functioning were affected very much (47%) or severely (11%) by relapses. Prescribed treatments for relapses included intravenous and/or oral corticosteroids (87%) and adrenocorticotropic hormone (13%). Nearly half of patients reported that their symptoms were very much (33%) or completely resolved (16%) following treatment. The most commonly reported adverse events were sleep disturbance (45%), mood changes (33%), weight gain (29%), and increased appetite (26%). Systematic assessment of relapses and response to relapse treatment may help clinicians to optimize outcomes for MS patients.

Relapses in multiple sclerosis (MS) are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the hypothalamic-pituitary-adrenal axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH) gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides [ACTH and α-, β-, γ-melanocyte-stimulating hormones (MSH)] and their receptors (Melanocortin receptors, MCRs) exert multiple actions, including modulation of inflammatory and immune mediator production. MCRs are widely distributed within the central nervous system and in peripheral tissues including immune cells (e.g., macrophages). This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

Background The majority of multiple sclerosis (MS) patients develop some form of lower urinary tract dysfunction, usually as a result of neurogenic detrusor overactivity (NDO). Patients identify urinary incontinence as one of the worst aspects of this disease. Despite the high prevalence of NDO, urological evaluation and treatment are significantly under-accessed in this population. The objectives of this study were: 1) to adapt the previously validated Actionable Bladder Symptom Screening Tool (ABSST) to a short form for ease and brevity of application in a clinical setting that is clinically meaningful; and 2) to develop a scoring algorithm that would be interpretable in terms of referring/considering precise diagnosis and treatment. Methods A US-based, non-randomized, multi-center, stand-alone observational study was conducted to assess the psychometric properties of the ABSST among patients who have MS with and without NDO. Mixed psychometric methods (e.g., classical statistics (Psychometric theory (3rd ed.). New York: McGraw-Hill; 1994) and item response methods (Applying the Rasch Model: Fundamental Measurement in the Human Sciences. New Jersey: Lawrence Earlbaum Associates; 2001)) were used to evaluate the predictive and clinical validity of the shortened form. The latter included clinicians flagging clinically meaningful items and associated response options which would indicate the need for further evaluation or treatment. Results A total of 151 patients, all with MS and with and without NDO, were recruited by 28 clinicians in various US geographical locations. Approximately 41% of patients reported a history of or currently having urinary incontinence and/or urinary urgency. The prediction model across the entire range of classification thresholds was evaluated, plotting the true positive identification rate against the false positive rate (1-Specificity) for various cut scores. In this study, the cut-point or total score of greater than or equal to 6 had a sensitivity of approximately 85%, and specificity of approximately 93% (i.e., 85% patients would warrant being referred to a urologist and 93% of the patients whose symptoms would not warrant urologist referral). Conclusions Overall the short form ABSST demonstrated sensitivity and specificity as it maintained the integrity of the longer form tool. Concurrent validity for each subscale as well as predictive and concurrent validity of the total shortened instrument was demonstrated. This instrument provides a new method for assessing bladder problems among MS patients, and may facilitate earlier and more precise diagnosis, treatment, and/or referral to a specialist.

Multiple sclerosis (MS) is a complex disease with a wide range of clinical manifestations. Current disease-modifying drugs (DMDs) are effective, but they are associated with effects that may negatively influence treatment compliance. A recent nursing advisory board of MS nurse experts from the Midwest discussed management approaches that can enhance DMD compliance and improve patient satisfaction and quality of life. One such approach is the use of patient questionnaires as tools to assess signs and symptoms of MS and treatment-related adverse effects. Information gained in this manner is beneficial to MS healthcare professionals as well as patients and has the potential to improve treatment compliance and outcomes and disease management.

Multiple sclerosis (MS) affects about 2.5 million people worldwide and about 400,000 in the United States.1 Although the disease course is variable, MS eventually causes considerable functional decline and morbidity as the disease progresses. Effective strategies in the care of patients with MS are multifaceted and involve early diagnosis and treatment in addition to symptom management, education, and providing a support system to improve or maintain patient adherence to MS therapies. It is essential that the clinician understand the value of early diagnosis and intervention, including the potential and relative benefits of disease-modifying therapies (DMTs). Clinicians can help patients with MS cope with symptoms resulting from MS, and also provide guidance for mitigating adverse effects (AEs) of therapy or supporting patient adherence to therapy when the patient questions the value of taking a DMT. In this supplement, Patricia Coyle, MD, begins by addressing evidence that early neurologic damage in MS may occur before lesions are detectable on MRI. This is especially important, because the accumulation of lesions over time is …

Multiple sclerosis (MS) is a chronic disease of the CNS and was described as early as the fourteenth century. Early attempts at treatment included primarily symptomatic therapies, but in the 1960s and 1970s the focus of research shifted to disease-modifying therapy (DMT). The first of these therapies to be approved by the FDA was interferon-beta1b (IFN-β1b) in 1993. Since that time there has been a significant expansion of research aimed at modifying the MS disease process. The present-day management of MS patients requires an understanding of an evolving therapeutic paradigm. In this paradigm, the efficacy, mechanisms of action, and effects of the available therapies intersect and are relevant to clinical practice. The efficacy of four of the DMTs—IFN-β1b SC, IFN-β1a SC and IM formulations, and glatiramer acetate SC—is well established, with some studies having over a decade of follow-up data.1–3 The practicing clinician should understand the differences in the administration and mechanisms of action of the DMTs and how these differences impact the clinical effects.4–6 The clinical effect of neutralizing antibodies (NAbs) and the risk for serious adverse effects of some DMTs (e.g., progressive multifocal leukoencephalopathy with natalizumab) are also factors that must be considered in …

Nurses play a critical role in caring for patients with multiple sclerosis (MS). The Multiple Sclerosis-Nurse Empowering Education (MS-NEED): European Survey was conducted to understand the role of nurses in MS and the provision of care across Europe. The survey focused on four key areas: clinical practice, advocacy, research and publication, and training and education. A total of 280 nurses were included from the UK, Germany, Italy, Poland, Finland and the Czech Republic. All participants were nurses actively working with MS patients. The role of the nurse in MS is diverse and varies substantially across Europe, leading to inequalities in patient care. A European consensus to define the roles and responsibilities of the MS nurse would facilitate consistency of care across all countries and help to achieve the best possible outcome for patients with MS in Europe. © TOUCH BRIEFINGS 2011.

Walking impairment is one of the most serious and frequent problems reported by multiple sclerosis (MS) patients. Treatments to restore walking ability are an unmet clinical need. Dalfampridine, a potassium channel blocker, is the first US Food and Drug Administration (FDA)-approved drug to be indicated specifically to improve walking in patients with MS. In clinical trials the drug showed improved walking speeds, demonstrating efficacy in all four types of MS. In phase III trials, dalfampridine provided significant benefits to 35–43% of treated patients. Therefore, it will be critical to manage patient expectations appropriately.