Neurology and Neurometabolic Unit Department of Neurological and Behavioral Sciences University of Siena Siena, Italy

Transcription

1 Nicola De Stefano Neurology and Neurometabolic Unit Department of Neurological and Behavioral Sciences University of Siena Siena, Italy Declared receipt of honoraria or consultation fees from Novartis, Merck, Biogen Idec, Roche. He declared to be member of a company advisor board, board of directors or other similar group: Novartis, Merck, Biogen Idec, Roche. He declared participation in a company sponsored speaker s bureau: Novartis, Merck, Genzyme

2 Outline Prognosticate and decide on treatment selection Support decision about switching therapy Relevance of MRI in NEDA Recognize early potential side effects of treatment

3 Patients reaching EDSS score 6.0 (%) MRI & Prognosis There is evidence that MRI lesion activity in early disease has prognostic value for estimating disability progression in natural history cohorts 1, Baseline MRI lesion number and clinical status at 20 years: proportion of patients reaching EDSS score n=31 n=20 n= Number of baseline lesions 18 6 n=34 1. Fisniku LK et al. Brain 2008;131: Brex PA et al. N Engl J Med 2002;346:158 64

4 MRI & Prognosis 10 lesions 4-10 lesions 1-3 lesions 10 lesions 4-10 lesions 0 lesions 1-3 lesions 0 lesions

5 Relevance of lesion location Sombekke et al Neurology 2013 Tintore et al Neurology 2010

6 Relevance of lesion location

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8 Each gauge represents a continuum from no concern (0 on the dial) through low, medium or high levels of concern Relapse MRI Progression Consider three low, two medium, or one high as an indication of possible suboptimal treatment that might warrant a change in management

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10 Responders Poor responders Poor Response defined as an increase of at least 1 point of EDD confirmed at 6 months

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12 Training set (PRISMS) Validation set (Barcelona) 2-3 (high risk) 1 0 (low risk)

13 MAGNIMS Score Multivariate analysis Cox Model in 1280 patients treated with IFN for 1y 95%CI Variables HR Lower Upper p NewT2 lesions= NewT2 lesions= NewT2 lesions= NewT2 lesions= NewT2 lesions= NewT2 lesions= NewT2 lesions= REL= REL= REL= Sormani et al, Neurology in press

14 MAGNIMS Score 0 1 Probability of progression = 19% Probability of progression = 28% 2 Probability of progression = 48% Total number of patients= 1280 Score 0 vs scores 1 or 2: PPV= 34%, NPV=83%, sensitivity=49%, specificity=70%, global accuracy=65%. Sormani et al, Neurology in press

15 NEDA - Definition Lately, the term disease-free status has been replaced by NEDA (No Evident Disease Activity) because of the limits of our ability to evaluate the full extent of underlying disease activity No disability progression No relapses No MRI activity Brain Atrophy? Other Biomarkers? NEDA has been evaluated in some MS clinical trials and few longterm studies of real-world MS cohorts

16 NEDA in Clinical Setting Long-term FU (7y) NEDA is difficult to sustain long-term even with treatment (only 17 of 216, 8%) maintained NEDA status after 7 years. Rotstein et al JAMA, Neurol 2015

17 NEDA in Clinical Setting Long Term FU (10y) NEDA-4 = 7/91 (8%) De Stefano et a,l Neurology 2015

18 Distinction Between MS and PML Lesions FLAIR Feature MS PML Shape Ovoid Diffuse Borders Well-circumscribed Ill-defined, infiltrative Size 3 5 mm Large >5 mm FLAIR=fluid-attenuated inversion recovery. Yousry TA et al. N Engl J Med. 354: ; data on file.

19 Distinction Between MS and PML Lesions FLAIR Feature MS PML Shape Ovoid Diffuse Borders Well-circumscribed Ill-defined, infiltrative Size 3 5 mm Large >5 mm Location Periventricular/ Dawson fingers Subcortical, finger-like projections Yousry TA et al. N Engl J Med. 354: ; data on file.

20 Distinction Between MS and PML Lesions Feature MS PML Shape Ovoid Diffuse Borders Wellcircumscribed Ill-defined, infiltrative Size 3 5 mm Large >5 mm Location Mass effect Persistence Periventricular/ Dawson fingers Yes for large lesions Resolves in approx 1 month Subcortical, finger-like projections No Progressively larger Yousry TA et al. N Engl J Med. 354: ; data on file.

21 MRI on PML DWI to detect new lesions T2W FLAIR DWI T2W and FLAIR both show lesions (areas of hyperintensity) but DWI shows a larger area of inflammation Comparison with prior MRI scans and DWI can be useful to determine whether the lesion is new PML=progressive multifocal leukoencephalopathy; MRI=magnetic resonance imaging; DWI=diffusion-weighted imaging; T2W=T2-weighted; FLAIR=fluid attenuated inversion recovery. data on file. Courtesy of Mike Wattjes

22 Take home message MRI provides good prognostic markers and can help to decide on treatment selection. Combination of both clinical and MRI measures is the best way to assess treatment response, with substantial increase in MRI being significant to establishing lack of response NEDA is an important therapeutic goal in MS care and a very interesting outcome measure for clinical trials. Clinical setting data have shown that NEDA is difficult to sustain in the long-term With specific treatments MRI should be used to monitoring safety and recognize early potential side effects of treatment

23 Take home message MRI provides good prognostic markers and can help to decide on treatment selection. Combination of both clinical and MRI measures is the best way to assess treatment response, with substantial increase in MRI being significant to establishing lack of response NEDA is an important therapeutic goal in MS care and a very interesting outcome measure for clinical trials. Clinical setting data have shown that NEDA is difficult to sustain in the long-term With specific treatments MRI should be used to monitoring safety and recognize early potential side effects of treatment

24 Take home message MRI provides good prognostic markers and can help to decide on treatment selection. Combination of both clinical and MRI measures is the best way to assess treatment response, with substantial increase in MRI being significant to establishing lack of response NEDA is an important therapeutic goal in MS care and a very interesting outcome measure for clinical trials. Clinical setting data have shown that NEDA is difficult to sustain in the long-term With specific treatments MRI should be used to monitoring safety and recognize early potential side effects of treatment

25 Take home message MRI provides good prognostic markers and can help to decide on treatment selection. Combination of both clinical and MRI measures is the best way to assess treatment response, with substantial increase in MRI being significant to establishing lack of response NEDA is an important therapeutic goal in MS care and a very interesting outcome measure for clinical trials. Clinical setting data have shown that NEDA is difficult to sustain in the long-term With specific treatments MRI should be used to monitoring safety and recognize early potential side effects of treatment