Disease Modifying Therapies (DMTs) in Multiple Sclerosis

Transcription

1 Disease Modifying Therapies (DMTs) in Multiple Sclerosis Gary Stobbe, MD Medical Director, MS Project ECHO Clinical Assistant Professor, UW Neurology

2 Conflict of Interest Dr. Stobbe has no conflicts of interest to disclose

3 Objectives Identify optimal time to initiate treatment of MS Review current MS DMTs Review strategies in choosing specific DMTs Recognize factors that influence changing therapies

4 MS Treatment 4

5 Case B - Overview 29 yo single mother, 2011 establishing care with newly diagnosed RRMS no relevant prior hx/family hx 2009 diffuse sensory sx neck area, then progressive sx R>L ON, no IVMP b/o delay in diagnosis ON. Outside brain and C-spine MRI negative. Mid 2010 abdominal cramping and rectal urgency w/o identified etiology x 3m Dec 2010 progressive sensory sx RUE, R torso, RLE x 3 weeks Mar 2011 numbness L hand x 1m May 2011 R ON, L hand numbness, Lhermitte Brain MRI: Multifocal WM lesions c/w MS, at least 4 enhancing lesions Neuro-ophthalomology: agree ON 3 day IVMP

6 Who Benefits from DMTs?

7 Subclinical CIS Relapsing-Remitting Secondary Progressive Who Benefits from DMTs? Neurological symptoms MRI lesions Time

8 DMTs are not a cure but: Goals of DMTs Relapse rate Relapse severity MRI lesion burden Accumulation of disability Progression of atrophy Individual treatment response difficult to predict

9 Sustained symptoms / Disability Window of opportunity Treatment at diagnosis Later treatment Natural Course of MS Disease onset Time Early treatment is better than late treatment Treatment is better than no treatment

10 The Evolving Landscape of DMTs

11 SELF-INJECABLES Interferon-beta 1a/b Avonex Betaseron, Extavia Rebif Glatiramer acetate Copaxone Fingolimod Gilenya ORAL AGENTS Terflunimide Aubagio Dimethyl fumerate Tecfidera Peg-IFN-beta 1a Plegridy INFUSIONS Mitoxantrone Novantrone Natalizumab Tysabri Alemtuzumab Lemtrada OFF-LABEL USE Cyclophosphamide Rituximab Stem cell transplantation m PHASE III Laquinimod Ocrelizumab Daclizumab

12 Choosing a DMT: Factors to Consider No established guidelines Disease activity high lesion load, pyramidal/brainstem symptoms poor recovery, short relapse interval, male, African American Side effects Monitoring Risk tolerance Patient preference (injectable, frequency) Insurance coverage

13 Case B DMT Relapsing-remitting MS by McDonald criteria in 2011 with onset of dz in 2009 Clinical and MRI progression while on various DMTs, hesitancy to switch DMTs Betaseron 7/2011-8/2012 with clinical and MRI progression Tysabri 8/2012-2/2013 dc ed for pt's concerns PML for JCV ab conversion early 2013 (index 0.39) despite notable rx benefit with resolution of multiple sx Pulse IVMP 2/13-4/13 awaiting transition to Tecfidera Tecfidera 4/ /2014 w/ monthly IVMP 7/ /2014 b/o clinical and MRI dz activity and while 3m TB treatment for h/o incompletely rx latent TB Brain MRI 7/2013: multiple new and gd+ brain lesions, 3 new gd+ c-spine lesions Brain MRI 7/2014: >10 gd+ lesions, significant progression b/c-spine Clinical dz activity at least 7/2013, 11/ /2013 Currently Gilenya since 11/2014

14 No established guidelines Choosing a DMT Clinical decision-making, not established algorithm

15 Changing DMTs Tolerability (side effects, risk management) Adherence Efficacy (breakthrough disease) Relapses Disability progression (neurologic exam) MRI activity: enhancing lesions new/enlarging lesions Prosperini et al. 2009

16 What About Benign MS? No accepted definition of benign MS EDSS <3.0 at 10 years (determined in retrospect) about 15% of MS patients no good predictive biomarkers Benign at 10 years - 21% required cane at 20 years Benign at 20 years - 15% required cane at 25 years (Sayao et al. 2011, 2007) Underestimation of non-motor deficits Cognitive impairment, depression, fatigue (Amato et al. 2006)

17 Resources The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. A Consensus Paper by the Multiple Sclerosis Coalition: MS Emerging Therapies Collaborative MS Diagnosis, Disease and Symptom Management app- DMTs Professional Resource Center Care/Managing-MS/Disease-Modification UW MEDCON (WWAMI): For your Patients: MS Navigator Program (1-800 FIGHT MS)

18 Disease Modifying Therapies

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20 Dr. Kristin Mitchell s Case 61, female, RRMS since 2000 MRI stable: , 2010, 2011, 2012 DMTs: Tecfidera: Summer 2014, stopped due to infection risk and concern/zoster Avonex: Stopped 2003 due to worsened depression, weakness/fatigue/r eye vision flicker Rebif: Unclear when this was stopped. Stopped due to eczema

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