Improving multiple sclerosis management and collecting safety information in the real world: the MSDS3D software approach

We employed clinical and magnetic resonance imaging (MRI) measures in combination, to assess patient responses to interferon in multiple sclerosis.

Despite important advances in the treatment of multiple sclerosis (MS) over recent years, the introduction of several disease-modifying therapies (DMTs), the burden of progressive disability and premature mortality associated with the condition remains substantial. This burden, together with the high healthcare and societal costs associated with MS, creates a compelling case for early treatment optimization with highly efficacious therapies. Often, patients receive several first-line therapies, while more recent and in part more effective treatments are still being introduced only after these have failed. However, with the availability of highly efficacious therapies, a novel treatment strategy has emerged, where the aim is to achieve no evidence of disease activity (NEDA). Achieving NEDA necessitates regular monitoring of relapses, disability and functionality. However, there is only a poor correlation between conventional magnetic resonance imaging measures like T2 hyperintense lesion burden and the level of clinical disability. Hence, MRI-based measures of brain atrophy have emerged in recent years potentially reflecting the magnitude of MS-related neuroaxonal damage. Currently available DMTs differ markedly in their effects on brain atrophy: some, such as fingolimod, have been shown to significantly slow brain volume loss, compared to placebo, whereas others have shown either no, inconsistent, or delayed effects. In addition to regular monitoring, treatment optimization also requires early intervention with efficacious therapies, because accumulating evidence shows that effective intervention during a limited period early in the course of MS is critical for maintaining neurological function and preventing subsequent disability. Together, the advent of new MS therapies and evolving management strategies offer exciting new opportunities to optimize treatment outcomes.

Background Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting. Objective To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS). Methods The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings. Results In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11–44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years. Conclusions Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice. Trial registration number NCT00493298.