Lessons from randomised direct comparative trials.
ABSTRACT For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-beta preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-beta in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-beta 1a sc 44 microg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-beta 1b sc 500 microg, interferon-beta 1b sc 250 microg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of beta-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate and high-dose interferon-beta preparations have comparable clinical efficacy.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease with both clinical and pathological heterogeneity. The complexity of the MS population has offered challenges to the measurement of MS disease progression in therapeutic trials. The current standard clinical outcome measures are relapse rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite (MSFC). These measures each have strengths and some weakness. Two additional measures, the six-minute walk and accelerometry, show promise in augmenting current measures. MS therapeutics is a quickly advancing field which requires sensitive clinical outcome measures that can detect small changes in disability that reliably reflect long-term changes in sustained disease progression in a complex population. A single clinical outcome measure of sustained disease progression may remain elusive. Rather, an integration of current and new outcome measures may be most appropriate and utilization of different measures depending on the MS population and stage of the disease may be preferred.Therapeutic Advances in Neurological Disorders 07/2010; 3(4):229-39.
- New England Journal of Medicine 02/2010; 362(5):456-8. · 51.66 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Objective: The prevalence of multiple sclerosis (MS) in Latin America varies across different studies but an intermediate risk and increased frequency of the disease have been reported in recent years. The circumstances of Latin American countries are different from those of Europe and North America, both in terms of differential diagnoses and disease management.Methods: An online survey on MS was sent to 855 neurologists in nine Latin American countries. A panel of nine experts in MS analyzed the results.Results: Diagnostic and therapeutic recommendations were outlined with special emphasis on the specific needs and circumstances of Latin America. The experts proposed guidelines for MS diagnosis, treatment, and follow up, highlighting the importance of considering endemic infectious diseases in the differential diagnoses of MS, the identification of patients at high risk of developing MS in order to maximize therapeutic opportunities, early treatment initiation, and cost-effective control of treatment efficacy, as well as global assessment of disability.Conclusions: The experts recommended that healthcare systems allocate a longer consultation time for patients with MS, which must be conducted by neurologists trained in the management of the disease. All drugs currently approved must be available in all Latin American countries and must be covered by healthcare plans. The expert panel supported the creation of a permanent forum to discuss future clinical and therapeutic recommendations that may be useful in Latin American countries.Therapeutic Advances in Neurological Disorders 11/2011; 4(6):349-60.