Managing the symptoms of multiple sclerosis: a multimodal approach.

BACKGROUND: Patients with multiple sclerosis (MS) may experience numerous symptoms, including spasticity, fatigue, cognitive dysfunction, depression, bladder dysfunction, bowel dysfunction, sexual dysfunction, and pain. OBJECTIVE: This article reviews the pharmacologic and nonpharmacologic interventions used to manage the symptoms of MS and discusses how interventions for a particular MS symptom may have an impact on other symptoms. METHODS: The English-language literature was reviewed through November 2005 using MEDLINE and the Cochrane Database of Systematic Reviews, with no restriction on year. The search terms included multiple sclerosis, disease-modifying therapies, adverse events, and combinations of multiple sclerosis with terms such as spasticity, fatigue, depression, mood disorders, pain, bladder dysfunction, bowel dysfunction, sexual dysfunction, cognitive dysfunction, and quality of life. RESULTS: The numerous options for the treatment of MS symptoms have shown varying degrees of efficacy and tolerability. Certain symptoms, if left untreated, may precipitate exacerbation of others. For example, spasticity may lead to pain and bladder and bowel dysfunction, whereas fatigue can compromise cognitive function. Similarly, the adverse effects of treatments for certain symptoms may further compromise other aspects of function. For example, the use of antidepressants may lead to sexual dysfunction, and treatments for spasticity and pain may cause sedation, which can worsen fatigue, cognitive dysfunction, and depressed mood. CONCLUSIONS: MS is associated with numerous symptoms that can be adversely affected by each other and by therapeutic interventions. Careful clinical monitoring and individualization of pharmacologic and non-pharmacologic therapies are recommended to manage the symptoms of MS, with the goals of improving or maintaining function and preserving the patient's quality of life.

A multimodal approach to managing the symptoms of multiple sclerosis.

Multiple sclerosis (MS) is a disease of the CNS with a challenging clinical course characterized by heterogeneous symptoms related to inflammation and demyelination. Disease-modifying agents (DMAs) are used to treat the related neuronal degradation. Certain symptoms occur regularly, although with variable frequency, regardless of treatment with DMAs. Because there is no cure for MS at this time, symptom management is critically important to quality of life. Symptoms commonly seen are spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction. Other symptoms include depression, bowel dysfunction, paroxysmal symptoms, and weakness. The symptom management model that provides optimal results for patients with MS is a multimodal approach using effective communication, patient education, physical modalities and activities, occupational and other therapies, and pharmacologic interventions. Individualizing treatment for each patient involves gaining control of symptoms as early as possible to prevent cycles of symptoms from developing.

Neutralizing antibodies to multiple sclerosis treatments.

OBJECTIVE: This article reviews the incidence and clinical significance of neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS) undergoing treatment with interferon beta (IFNbeta). Implications for practice are also discussed in light of the currently available data on the clinical consequences of NAbs in patients with MS. SUMMARY: As with other recombinant protein drugs used for the treatment of a number of diseases, antibodies commonly develop to IFNbeta products during the treatment of patients with MS. Neutralizing antibodies (NAbs) are a subset of antibodies that reduce or diminish the biologic activity of IFNbeta. Three formulations of IFNbeta are currently available for the treatment of relapsing-remitting MS: IFNbeta-1b (Betaseron), intramuscular (i.m.) IFNbeta-1a (Avonex), and subcutaneous (s.c.) IFNbeta-1a (Rebif). Individual phase III clinical trials and direct comparison studies have shown that NAbs develop more frequently during treatment with IFNbeta-1b than IFNbeta-1a and that between the 2 IFNbeta-1a products, NAbs develop more frequently during treatment with s.c. IFNbeta-1a than IM IFNbeta-1a. Data from clinical trials of IFNbeta products indicate that clinical efficacy of IFNbeta is reduced in NAb-positive patients. CONCLUSION: In light of these data, the immunogenicity of IFNbeta products should be considered prior to initiating treatment with IFNbeta. Also, ongoing laboratory monitoring of patients treated with higher-dose IFNbeta is recommended for early detection of NAbs.

Stepped-care approach to treating MS: a managed care treatment algorithm.

OBJECTIVE: To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. SUMMARY: MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.