Innovazione e personalizzazione nella terapia della SM. Rocco Totaro Centro per la Diagnosi e Cura delle Malattie Demielinizzanti L Aquila

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1 Innovazione e personalizzazione nella terapia della SM Rocco Totaro Centro per la Diagnosi e Cura delle Malattie Demielinizzanti L Aquila

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10 Which are the objectives of MS treatment? «Historically» the objective of MS treatment was to reduce relapse rate and consequences in terms of disability Today, the scientific community agrees that the therapeutic choice should be driven by the aim to reduce the overall disease activity, both clinical and sub-clinical, and not only by the clinical importance of relapses

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17 New natural history of interferon Beta treated relapsing multiple sclerosis Trojano M. et al. Ann. Neurol. 2007

18 RR-MS patients show breakthrough diseases within 2 years of IFN or GA treatment Data from published Phase III trials 1 relapse 50-75% Sustained EDSS progression 20-30% 1 GD+ lesion 25-30% 1 New T2 Lesion 50-70% Breakthrough disease is expected in patients despite treatment with firstline DMDs: data from phase III studies showed that about 2/3 of patients with RR-MS had relapses or new MRI lesions within 2 years of starting IFNB or GA. Rudick RA, Polman CH. Lancet Neurol 2009

19 Types of treatment response DMT treated patients Optimal response Non responder Sub optimal responder Patients continue current DMT Escalation vs lateral switching

20 It is essential to identify the non-response to treatment as early as possible Early identification of non-response allows a timely switch to an alternative treatment before the disease progresses to a point where new treatments are no longer effective substantial neurological damage occurs

21 Treatment response evaluation: which tools can be used? Rudick RA, Polman CH. Lancet Neurol 2009

22 MRI outcomes at 6-12 months of therapy are the best predictors of treatment response Rudick RA Defining interferon beta response status in multiple sclerosis patients. Ann Neurol 2004 Durelli et al. MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis. JNNP 2008 Rio J et al. Relationship between MRI lesion activity and response to IFN-beta in relapsing-remitting multiple sclerosis patients. Mult Scler 2008 Prosperini et al. One-year MRI scan predicts clinical response to Interferon Beta in multiple sclerosis. Eur J Neur 2009 Freedman M et al. Predictors of disease activity in CIS patients treated with IFNB-1b in the BENEFIT study. Mult Scler (Suppl) 2011 Bermel RA et al. Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta. Ann Neurol 2013 Prosperini L et al. Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis. Mult Scler 2013

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25 Recommendations for determining the level of concern when considering treatment modification based on relapses. Freedman MS et al. Can J Neurol Sci 2013

26 Recommendations for determining the level of concern when considering treatment modification based on disability progression Freedman MS et al. Can J Neurol Sci 2013

27 Recommendations for determining the level of concern when considering treatment modification based onannua MRI findings Freedman MS et al. Can J Neurol Sci 2013

28 The Canadian treatment optimization model: assessing concern whether to modify a treatment regimen Freedman MS et al. Can J Neurol Sci 2013

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30 Risk of new relapses and increase of disability during the period of follow-up (months 12 36) according the positivity for the different variables after 12 months of therapy R+ = relapse P+ = disability progression MRI+ = more than 2 active lesions

31 Risk of new relapses and increase of disability during the period of follow-up (months 12 36) according the positivity for the different variables after 12 months of therapy R+ = relapse P+ = disability progression MRI+ = more than 2 active lesions

32 Risk of new relapses and increase of disability during the period of follow-up (months 12 36) according the positivity for the different variables after 12 months of therapy R+ = relapse P+ = disability progression MRI+ = more than 2 active lesions

33 Sormani MP, De Stefano N. Nature Rev 2013 The Rio and Modified Rio scores

34 Modified Rio score = 0 No relapses and <5 new T2 lesions Low-risk (24%) Modified Rio score = 1 1 relapse or no relapses and >4 new T2 lesions Medium-risk (33%) Modified Rio score 2 >1 relapses or 1 relapse and >4 new T2 lesions High-risk (65%)

35 An evidence-based quantitative algorithm to monitor response to IFN-β based on the Modified Rio Score for the assessment of the risk of progression over 4 years in patients with multiple sclerosis treated for 1.5 years with IFN-β therapy. Sormani MP, De Stefano N. Nature Rev 2013

36 Probability of disability progression over 2 years in patients with multiple sclerosis enrolled in the PRISMS trial. The placebo group (blue line) is compared with the IFN-β treated group, which is split into responders (pink line) and non-responders (green line) as classified by the Modified Rio Score. Sormani MP, De Stefano N. Nature Rev 2013

37 Disease-free concept: NEDA, no evidence of disease activity % Free from relapse % Free from clinical activity % Free from disease progression % Free from any disease activity % Free from Gd+ lesions at MRI % free from MRI activity % Free from T2 lesions at MRI