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WHEN AND HOW TO START TREATMENT IN RELAPSING MS

Giancarlo Comi

MS Centre Gallarate Hospital, Gallarate, European Charcot Foundation

The importance of early treatment is now considered a fundamental step in relapsing multiple sclerosis (RMS). Pathological studies have revealed that acute axonal loss in white and grey matter lesions can be quite large, even in preclinical conditions; these observations have been confirmed by magnetic resonance imaging, evoked potentials and optical coherence tomography. On the other hand, inflammatory activity, the target of disease modifying treatmets (DMTs) in RMS, tend to be higher in the initial phases of the disease and decreases with the increase of disease duration. Clinical trials have revealed that DMTs have a stronger efficacy when used in patients with a first attack highly suggestive of MS with a signifcant impact in the risk of accumulating irreversible disability and brain atrophy. Data confirmed by observational studies.

The availability of DMTs with different profiles of efficacy and safety allow to select the appropriate treatment for each person with MS according to an accurate estimation of prognostic and predictive factors in combination with the informed preferences expressed by the patient. Recent developments of precision medicine supports the treatment personalisation in order to maximize benefits and minimize risks. Both more recent clinical trials where the new agent was tested against an active comparator, and well performed observational studies suggest that in treatment naif patients starting with a more aggressive treatment produces more short and long term benefits than using an escalating approach.

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Over the past two decades, an ever-expanding range of disease-modifying therapies (DMTs) has become available for multiple sclerosis (MS) on the basis of their efficacy in randomized controlled trials (RCTs). At the same time, the growing number of new DMTs has made treatment decisions more complicated in clinical practice. Major questions remain concerning long-term risks and benefits of therapies, risk stratification, treatment sequencing, benefits of different dosing and routes of administration and outcome definition. Post-marketing studies based on real-world (RW) data has gained attention as a good strategy for capturing important additional information to complement data from RCTs in order to address issues around the uncertainty of the evidence base. In the last years, the increasing amount of RW data collected in MS registries, administrative databases and health electronic records, the evolution in information technology infrastructure and the corresponding ability to store and process these data through new and more sophisticated statistical methods, drove an exponential growth of high quality post-marketing studies of MS treatments. These studies are providing insights into predictors of safety, tolerability and effectiveness of DMTs and the long-term comparative effectiveness between different DMTs that are proving to be critical in directing and improving MS intervention strategies in daily practice. Moreover post-marketing research, has become an integral part of the drug evaluation process for a wide range of agents. Regulatory bodies and pharma companies have stated their ambition for greater use of RWD for treatment decision making, post-approval surveillance studies and pricing and reimbursement decisions.