Biomedical subjects

William H Stuart

Publications and source records attributed to William H Stuart.

5 recordsLinked to original sources

PubMed2006

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. METHODS: We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. RESULTS: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients. CONCLUSIONS: Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.).

Adolescent↗

PubMed2004

Selecting a disease-modifying agent as platform therapy in the long-term management of multiple sclerosis.

Multiple sclerosis (MS) is a complex, incurable disease. Treatment consists of lifelong disease and symptom management. FDA-approved therapies for relapsing MS include subcutaneous (SC) interferon beta-1b (IFNbeta1b, Betaseron), IM interferon-beta-1a (Avonex), SC interferon-beta-1a (Rebif), glatiramer acetate (Copaxone), and mitoxantrone (Novantrone), all of which are known as disease-modifying agents (DMAs). DMAs that can be initiated and continued on a long-term basis can be referred to as platform therapies. During periods of disease instability with increased disease activity, corticosteroids or immunosuppressive agents can be used in combination with appropriate DMA platform therapy to help control symptoms. To date, long-term comparative studies of DMAs are not available. However, based on the effects of these agents on disability progression, relapse rates, MRI outcomes, and neutralizing antibodies observed in phase III randomized clinical trials, IFNbeta1a products are the DMAs of choice for platform therapy for MS. Evidence indicates that IFNbeta1a may also be beneficial in the early stages of the disease. Research is ongoing to identify other appropriate add-on agents (e.g., antigen-specific therapies) to be used in combination with existing DMAs to effectively manage MS.

Antibody Formation↗

PubMed2004

Concomitant therapy for multiple sclerosis.

Interferon beta (IFNbeta) is the first-line treatment for patients diagnosed with multiple sclerosis (MS). In patients with MS who experience breakthrough disease while receiving treatment with IFNbeta, it is common clinical practice to administer additional therapeutic agents. The rationale for use of concomitant therapies in the long-term management of MS is derived from the heterogeneous and multifactorial etiology of this disease. Agents used concomitantly have the potential to exert synergistic effects and slow the progression of disease in patients who experience breakthrough disease. Concomitant therapies that have been reported in patients with MS are reviewed here.

Drug Therapy, Combination↗

PubMed2004

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.

Adjuvants, Immunologic↗

PubMed2004

Clinical management of multiple sclerosis: the treatment paradigm and issues of patient management.

OBJECTIVE: To summarize the conclusions of an expert panel of neurologists specializing in multiple sclerosis (MS) convened for the purpose of creating a treatment algorithm with regard to the clinical management of MS. The panel was sponsored by the Health Science Center for Continuing Medical Education and the University of Medicine and Dentistry of New Jersey and supported by an educational grant from Biogen Idec, Inc. SUMMARY: MS is a chronic demyelinating disease characterized by a variable clinical course. Currently, there is no cure for MS, and the management of MS requires lifelong treatment with disease-modifying agents. Some patients respond well to therapy for many years, whereas others may have aggressive disease that is more difficult to manage. Hence, given the variable nature in the course of MS and patients. response to treatment, neurologists must individualize care for their patients. An MS treatment algorithm was recently developed by a panel of neurologists who are MS experts to provide community neurologists with best-practice protocols for treating and managing their MS patients. The panel of experts categorized MS into 3 different stages, with patients transitioning between the stages based on their response to therapy and disease progression. Stage I represents MS early in the progression of the disease, during which platform drug therapy is recommended (i.e., interferon beta-1b [IFNbeta-1b], IFNbeta-1a, or glatiramer acetate). The results of randomized, controlled clinical trials suggest that IFNbeta is the optimal choice for platform therapy. Despite treatment with platform therapy, it is common for patients to experience some ongoing symptoms and periodic exacerbations of the disease (annual relapse rate of 0.59 to 0.84 on treatment); such relapses should not be considered treatment failures and are best managed with steroids. Stage II represents acute breakthrough disease (i.e., when the clinical activity becomes more frequent or severe). This stage is best managed by the addition of pulse corticosteroids to the platform drug. Stage III represents continued breakthrough disease and is best managed by the addition of immunosuppressants to the platform drug. CONCLUSION: The MS treatment algorithm provides an educational resource for physicians. It should assist all health care professionals involved in the management of MS patients and enhance their ability to improve quality of life for these patients over the course of the disease.

Adjuvants, Immunologic↗