Practical Clinical Guidelines for Natalizumab Treatment in Patients With Relapsing Multiple Sclerosis.

Natalizumab (TYSABRI®) was the first high-efficacy monoclonal antibody disease-modifying therapy (DMT) approved as a monotherapy for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Because natalizumab is administered by intravenous infusion, infusion nurses play a key role in the care of natalizumab-treated patients. In the 16 years since approval, substantial data have been gathered on the long-term, real-world effectiveness and safety of natalizumab. This article provides a synopsis of this data, as well as practical information for optimizing patient care. This includes information on strategies to mitigate the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients, natalizumab use during pregnancy, and use with vaccines. It also includes guidance on the preparation and administration of natalizumab and monitoring of natalizumab-treated patients.

Persistent severe lymphopenia 5 years after dimethyl fumarate discontinuation.

One known adverse event associated with dimethyl fumarate (DMF) is grade III lymphopenia which usually resolves within 2-3 months upon DMF discontinuation. Here, we report a case of a 50-year-old woman with MS who developed grade III lymphopenia within 6 months of DMF initiation, and despite treatment cessation within the next 6 months, she has continued to have severe persistent lymphopenia for over 5 years. Our observation suggests prolonged and possibly irreversible lymphopenia as a possible adverse event of DMF, and it emphasizes the need for monitoring lymphocyte numbers, and to cease dosing promptly after onset of grade III lymphopenia.

Acute relapse after initiation of Siponimod in a patient with secondary progressive MS.

Sphingosine 1-phosphate (S1P) is a signaling molecule that binds to five G protein-coupled receptors (Proc Natl Acad Sci USA 108:751-756, 2011). Modulation of these receptors has been associated with pleiotropic biological effects in the immune, cardiovascular, and central nervous systems (CNS). The functional S1P receptor antagonist fingolimod was the first member of this class of pharmacotherapeutics to be approved for treatment of relapsing multiple sclerosis (MS). Siponimod is currently in clinical trial in patients with secondary progressive (SP) MS, a clinical trial for which there is an unmet need for disease-modifying agents. 10 weeks into the trial, the patient awoke with blurry vision in his left eye, and was subsequently diagnosed with an acute optic neuritis. Despite discontinuation of siponimod and treatment with pulse corticosteroids, the patient did not regain visual function in the affected eye. This is the first report of disease reactivation shortly after initiating siponimod in a patient with SPMS. This case illustrates that the known changes in lymphocyte numbers and composition in the CNS associated with S1P receptor antagonism during the SPMS disease stage may have adverse outcomes in some patients during treatment initiation, and that close clinical and paraclinical monitoring is advised.

Nurses' perspective on approaches to limit flu-like symptoms during interferon therapy for multiple sclerosis.

BACKGROUND: Several interferon beta (IFNß) formulations are approved for first-line use as disease-modifying therapies to treat patients with multiple sclerosis (MS). Systemic post-injection reactions, often termed flu-like symptoms (FLS), occur in approximately half of all patients treated with IFNßs and can affect adherence to therapy. These symptoms, which include pyrexia, chills, malaise, myalgia, and headaches, usually resolve within 24 hours or persist intermittently following each injection. Because FLS, which usually occur early in the treatment course and diminish over time, are a primary cause of nonadherence to IFNß therapy, it is important to employ strategies that can attenuate these side effects. METHODS: To identify interventions effective in limiting FLS, a panel of United States-based nurses with expertise in MS patient care was convened and a literature review completed. RESULTS: Panel consensus was reached on specific interventions that can attenuate FLS. These prevention and mitigation strategies include dose titration, analgesia, and optimal injection timing, as well as other techniques that panel members have found useful in their clinical practice experience. CONCLUSIONS: These measures, in addition to effective patient education, will help to reduce the incidence of FLS secondary to IFNß therapy, improve patient medication adherence, and positively affect long-term clinical outcomes.

Best practices in multiple sclerosis: infusion reactions versus hypersensitivity associated with biologic therapies.

Infusion nurses are uniquely positioned to play a vital role in the early identification and management of infusion and hypersensitivity reactions during the administration of biologic therapies. This article reviews the current evidence regarding reactions related to the administration of monoclonal antibodies, namely, natalizumab, a humanized monoclonal antibody against the cellular adhesion molecule alpha4-integrin, in patients with multiple sclerosis. In addition to differentiating between infusion and hypersensitivity reactions, the article presents general guidelines for the management of these reactions and provides case studies to better illustrate the use of appropriate interventions.

A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events.

BACKGROUND: In a chronic disabling disorder such as multiple sclerosis (MS), adherence to treatment is of critical importance in maximizing benefits of therapy over the long term. Adverse events (AEs) are often cited by patients who discontinue therapy. METHODS: Databases including Medline, CINAHL, and International Pharmaceutical Abstracts were searched for literature pertaining to adherence and AEs in MS published between January 1970 and August 2008. Clinical studies and case reports of AEs were included, as were papers that outlined factors that influence adherence. An advisory board with extensive experience in managing patients with MS developed guidelines to assist healthcare providers in maximizing adherence to disease-modifying therapy. DISCUSSION: Internally based factors such as self-image, and externally based factors such as AEs, may influence patients' willingness and ability to adhere to therapy. Management of AEs associated with disease-modifying therapies and other therapies is reviewed, including intramuscular and subcutaneous interferon beta (IFNbeta)-1a, IFNbeta-1b, glatiramer acetate, natalizumab, methylprednisolone, mitoxantrone, cyclophosphamide, methotrexate, azathioprine, and intravenous immunoglobulin. CONCLUSIONS: Effective management of MS is an ongoing, dynamic process that can enhance patients' adherence to therapy. Healthcare practitioners may address factors influencing adherence among patients with MS by managing treatment expectations, maintaining good communication with the patient, and managing AEs of treatment. Although the guidelines proposed herein originate from a single advisory board, it seems clear that by addressing patient concerns, healthcare practitioners can work with patients to enhance their ability to continue to adhere to their therapies and thereby gain the benefits of their treatment over the long term.

Disease-modifying therapy in multiple sclerosis: strategies for optimizing management.

BACKGROUND: The objective for this article is to highlight several challenges faced by patients and providers in the utilization of disease-modifying agent (DMA) therapy in multiple sclerosis (MS) and to offer practical management strategies that can effectively mitigate or even prevent limiting adverse reactions and enhance treatment compliance. REVIEW SUMMARY: Our discussion will be limited to the use of interferon beta1a (Avonex, Rebif), interferon beta1b (Betaseron), and glatiramer acetate (Copoxane) as these are the primary agents used in the United States for primary disease-modifying therapy in relapsing forms of MS. Some of the recommendations contained herein are derived from evidence-based studies, while others are contingent upon our collective clinical experiences. At the University of Texas Southwestern Medical Center at Dallas and Texas Neurology in Dallas we actively follow approximately 5000 MS patients. The majority of our patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) are treated with one of the currently available DMAs. Our experience with these patients, and the challenges they face in continuing long-term treatment, constitutes the basis of our proposed treatment strategies. As part of this effort we formulated an assessment and intervention instrument that can be used in the clinic and by telephone to enhance compliance and minimize adverse events. CONCLUSION: A comprehensive treatment approach to the utilization of disease-modifying therapy in MS can serve to optimize the management of our patients and effectively meet the challenges that arise during the course of treatment.