Achieving New Treatment Goals in Multiple Sclerosis Strategies for Initial Treatment Selection and Patient Engagement. Dayton, OH

Transcription

1 A CME/CE-certified Symposium held in conjunction with the 2018 Annual Meeting of the CMSC Jointly provided by: In collaboration with: This program was supported by an educational grant from Sanofi Genzyme. Program Faculty Suhayl Dhib-Jalbut, MD Professor and Chairman, Department of Neurology Rutgers NJ Medical School Newark, NJ Robert Wood Johnson Medical School New Brunswick, NJ Machteld E. Hillen, MD Associate Professor Director, Adult Neurology Clinic and Neurology Residency Program Department of Neurology Rutgers NJ Medical School Newark, NJ Community Manager Alina Ahsan Health Union, LLC MultipleSclerosis.net Philadelphia, PA Patient Advocate Laura Kolaczkowski MultipleSclerosis.net Dayton, OH 2018 Rockpointe Page 1

2 Disclosures Program Faculty The faculty reported the following relevant financial relationships that they or their spouse/partner have with commercial interests: Suhayl Dhib-Jabut, MD Consultant/Independent Contractor: Celgene; Grant/Research Support: Biogen, Teva Machteld E. Hillen, MD Grant/Research Support: Genentech Alina Ahsan Nothing to disclose Laura Kolaczkowski Nothing to disclose Non-faculty Content Contributors Non-faculty content contributors and/or reviewers reported the following relevant financial relationships that they or their spouse/partner have with commercial interests: Chad Williamson, MS, MBA, CMPP; Blair St. Amand; Lindsay Scott, PT, DPT, ATC: Nothing to disclose The planners, reviewers, and staff at the Consortium of Multiple Sclerosis Centers in a position to influence content have disclosed no relevant financial relationships. Educational Objectives At the conclusion of this activity, participants should be able to demonstrate the ability to: Recognize the benefits of starting an optimal DMT early enough to achieve the new treatment goal of no evidence of disease activity (NEDA) Apply current evidence to select a personalized disease-modifying treatment approach with appropriate modifications based on disease activity Implement practical strategies for improving patient engagement in management plans 2018 Rockpointe Page 2

3 Multiple Sclerosis An Immuno-genetic Disease Suhayl Dhib-Jalbut, MD Multiple Sclerosis: An Immuno-genetic Disease Genetic Predisposition Twins studies HLA-DR2 (DRß1*1501) (antigen presentation) IL-2Ra (regulatory T-cells) IL-7Ra (memory T-cells) GWAS (>100 alleles) Images courtesy of Dhib-Jalbut S Immune Dysregulation MS Environmental Factors Demographics/Epidemics Microbial Agents EBV Vitamin D Smoking Salt BMI Microbiome 2018 Rockpointe Page 3

4 T- and B-cells Coordinate Immune Attack in MS T-cell immune functions B-cell immune functions BBB = blood-brain barrier; CSF = cerebrospinal fluid; MMP-3 = matrix metalloproteinase-3; NK = natural killer; ROS = reactive oxygen species; Th = helper T; Treg = regulatory T Claes N et al. Front Immunol. Accessed 11/8/17. Alvermann S et al. JAMA Neurol. 2014;71: Dittel BN et al. Brain Behav Immun. 2008;22: Severson C, Hafler DA. Results Probl Cell Differ. 2010;51: MS Treatment Goals: No Evidence of Disease Activity (NEDA) Machteld Hillen, MD 2018 Rockpointe Page 4

5 No Evidence of Disease Activity (NEDA) NEDD (No Evidence of Detectable Disease) replaced the term cure in oncology, and is used in other fields as well (rheumatology) 2013 NEDA was proposed to replace the term Disease Free Activity (DFA), based on clinical-trial outcomes already in use 15 years of NEDA was proposed as a definition for MS cure Banwell B et al. Mult Scler Relat Disord. 2013;2: NEDA-3 or NEDA No clinical relapses No EDSS progression (12 weeks or 6 months in some trials) No MRI activity (new or enlarging T2 lesions or Gd-enhancing lesions) Adopted as a treatment target in 2013 EDSS = Expanded Disability Status Scale; Gd = gadolinium; MRI = magnetic resonance imaging, NEDA = no evidence of disease Giovannoni G et al Mult Scler Relat Disord. 2018;20: Rockpointe Page 5

6 Related Terminology NEDA Definitions Level NEDA 3 Criteria No clinical relapses + no EDSS confirmed disability progression + no MRI activity NEDA 4 NEDA 3 + annualized percentage brain volume loss -0.4% NEDA 5 MEDA NEPAD NEDA 4 + CSF neurofilament Minimal evidence of disease activity e.g. using the Rio Score (Rio et al. 2006), Modified Rio Score (Sormani et al. 2013) No evidence of progression or active disease NEDA 3 + no 12-week confirmed progression of 20% on the timed 25-foot walk test and on the 9-hole peg test Lu G et al. Mult Scler Relat Disord. 2018;20: NEDA at 10 Years Observational Study MRI 7% EDSS 3% 14% 24% 34% 9% EDSS = Expanded Disability Status Scale; MRI = magnetic resonance imaging; NEDA = no evidence of disease; REL = relapse. De Stefano N et al. Neurology. 2015;85: % REL 1% 91 patients, 55% (50/91) no progression, 33% (30/91) no relapse, 21% (19/91) no MRI, 9% (8/91) NEDA MRI+ = 72/91 (79%) REL+ = 61/91 (67%) EDSS+ = 41/91 (45%) 8/91 (9%) = NEDA 31/91 (34%) = MRI+, REL+ and EDSS+ 22/91 (24%) = MRI+ and REL+ 6/91 (7%) = MRI+ and EDSS+ 1/91 (1%) = REL+ and EDSS+ 13/91 (14%) = MRI+ only 7/91 (8%) = REL+ only 3/91 (3%) = EDSS+ only 2018 Rockpointe Page 6

7 NEDA at 7 Years in CLIMB Observational Study of 219 Patients NEDA at 1 year 46% (99/215), NEDA at 2 years 27.5% (60/218), NEDA at 7 years 7.9% (17/216) 56.5% (117/207) had no progression, 24.2% (52/215) had no MRI activity, and 23% (49/213) had no relapse at 7 years NEDA at 2 years has a positive predictive value, 78.3% of no disability at 7 years (better predictor than each indicator alone) Rotstein DL et al. JAMA Neurol. 2015;72: NEDA in Randomized Controlled Trials Post-hoc Analysis of NEDA-3 in Clinical Trials Study Duration (years) Percent NEDA ADVANCE 1 34% peginterferon-ß*** 15% placebo AFFIRM 1 47% natalizumab*** 15% placebo SELECT 1 39% daclizumab*** 11% placebo FREEDOMS/FREEDOMSII 2 31% fingolimod*** 10% placebo AFFIRM 2 37% natalizumab*** 7% placebo DEFINE/CONFIRM 2 23% dimethyl fumarate*** 11% placebo TEMSO 2 23% teriflunomide 14 mg*** 14% placebo 18% teriflunomide 7 mg* CARE-MSI a 2 39% alemtuzumab** 27% interferon-ß CARE-MSII a 2 32% alemtuzumab*** 14% interferon-ß OPERA I a 2 48% ocrelizumab*** 29% interferon-ß OPERA II a 2 48% ocrelizumab*** 25% interferon-ß P-value for study DMS vs comparator * <0.05; ** <0.01; ***P-value < a Pre-specified endpoint. Parks NE et al. J Neurol Sci. 2017;383: Rockpointe Page 7

8 NEDA and Interferon Beta-1a NEDA in SET Trial (CIS) 40.1% at year % at year 4 NEDA at ASA Trial (RRMS) 20.4% at year 1 3.3% at year 4 0% at year 10 CIS = clinically isolated syndrome; RRMS = relapsed remitting multiple sclerosis Uher T et al. Multip Scler. 2017;23: NEDA (DAFS) and First-line Agents (COMBIRX) Disease Activity-free Status at Years 3, 4, and 6 (PDE) Interferon Beta-1a: NEDA at 3 years 20.5%, at 6 years 13.2% Glatiramer Acetate: NEDA at 3 years 20.4%, at 6 years 18.8% Both: NEDA at 3 years 32.1%, at 6 years 21% % Disease Activity Free Year 3: IFN+GA, P=0.002 IFN+GA vs IFN, P=0.001 IFN vs GA, P= DAFS = disease activity free status; EDSS = Expanded Disability Status Scale; GA = glatiramer acetate; INF = interferon; PDE = protocol-defined exacerbation; CUA = combined unique lesion activity Lublin FD et al. Multi Scler Relat Disord. 2017;18: Year 4: IFN+GA, P=0.014 IFN+GA vs IFN, P=0.033 IFN vs GA, P= Year 6: IFN+GA, P=0.10 IFN+GA vs IFN, P=0.018 IFN vs GA, P= Year 3 (740) Year 4 (500) Year 6 (261) No PDE + No EDSS Worsening + No CUA 18.8 IFN+GA IFN GA 2018 Rockpointe Page 8

9 NEDA and Peginterferon Beta-1a (ADVANCE) NEDA at 2 Years: 16% in Delayed Treatment, 37% (Q 2 Week Dosing) LOCF = last observed carried forward; MRI = magnetic resonance imaging; NEDA = no evidence of disease activity Arnold DL et al. BMC Neurology. 2017;17:29. NEDA and NEDA-4 in Fingolimod FREEDOMS and FREEDOMS II NEDA at 2 years fingolimod: 31%, NEDA-4 at 2 years: 19.7% CDP, confirmed disability progression; OR, objective response; CI, confidence interval; NEDA, no evidence of disease Kappos L et al. Mult Scler. 2016;22: Rockpointe Page 9

10 NEDA (DAF) and Natalizumab (AFFIRM) NEDA at 2 Years: Natalizumab 37%, Placebo 7% Proportions of Patients without Disease Activity Over 2 Years P<0.0001, natalizumab vs placebo, for all individual and combined disease measures. Havrdova E et al. Lancet Neurol. 2009;8: Placebo Natalizumab Absolute Difference (95% CI) No relapse 130/300 (43%) 422/598 (71%) 27.3% ( %) No progression 205/286 (72%) 486/581 (84%) 12.0% ( %) No relapse and no progression 117/301 (39%) 383/596 (64%) 25.4% ( %) No gadolinium-enhancing lesions 164/290 (57%) 553/583 (95%) 38.3% ( %) No new or enlarged T2 lesions 44/296 (15%) 342/593 (58%) 43.4% ( %) No gadolinium-enhancing lesions and no new or enlarged T2 lesions 42/296 (14%) 342/593 (58%) 43.5% ( %) No gadolinium-enhancing lesions, no new or enlarged T2 lesions, and no relapse 25/303 (8%) 244/600 (41%) 32.4% ( %) No radiological or clinical activity 22/304 (7%) 220/600 (37%) 29.5% ( %) NEDA (DAF) and Cladribine (CLARITY) 96 Week NEDA Cladribine:44% (3.5 mg), 46% (5.25 mg), and 16% placebo 100 P< P< P< P< / /406 P< P< Patients (%) / / / / / /360 60/379 0 Weeks 0-24 Weeks 0-48 Weeks 0-96 Giavannoni G et al. Lancet Neurol. 2011;10: Placebo Cladribine 3.5 mg/kg Cladribine 52.5 mg/kg 2018 Rockpointe Page 10

11 NEDA and Ocrelizumab in OPERA I and II 96 Week NEDA Interferon (INF) Beta-1a: 27.1% 96 Week NEDA Ocrelizumab: 47.7% Havrdova E et al. Mult Scler J Exp Transl Clin. 2018;4: NEDA and Alemtuzumab (CARE-MS I) CI = confidence interval; MRI = magnetic resonance imaging; NEDA = no evidence of disease activity Havrdova E et al. Neurology. 2017;89: Rockpointe Page 11

12 NEDA and Alemtuzumab (CARE-MS II) CI = confidence interval; MRI = magnetic resonance imaging; NEDA = no evidence of disease activity Coles AJ et al. Neurology. 2017;89: Autologous Stem Cell Transplant and NEDA NEDA at 2 Years 78%-83%, at 5 Years 60%-68% NEDA no evidence of disease activity. Sormani MP et al. Mult Scler. 2017;23: Rockpointe Page 12

13 Individualizing DMD Therapy in MS Suhayl Dhib-Jalbut, MD Existing and Emerging MS Therapies IFNβ-1b Approved Therapy Phase III completed In Phase III Other Approved Treatment IFNβ-1a IM injection Glatiramer acetate Mitoxantrone IFNβ-1a SC injection Natalizumab nd IFNβ-1b Dalfampridine Dextromethorphanquinidine Fingolimod Cladribine* Approval date *In March 2011, the FDA did not approve cladribine and requested Merck KGaA provide an improved understanding of its safety risks and overall benefit-risk profile. Teriflunomide 2012 Dimethyl fumarate Alemtuzumab 2013 Pegylated IFNβ-1a 2014 Laquinimod Cladebrine Laquinomod MD1003 (Biotin) Mastinib Ofatumumab Ozaninod Ponesimod Siponimod Ocrelizumab Rockpointe Page 13

14 MS Therapies Immunomodulators Cell migration inhibitors/ Lymphocyte sequesters Lymphocyte depleters Remyelinators Dimethyl fumarate GA IFN-beta Natalizumab Fingolimod Siponimod* B- and T-cells Alemtuzumab Daclizumab MD1003* (high-dose biotin) Teriflunomide Laquinamod* Ozanimod* Ponesimod* Mastinib* B-cells Ocrelizumab Ofatumumab *Investigational Multiple Sclerosis Association of America. Long-term treatments for multiple sclerosis. Updated April 13, Available from: Accessed May 1, Long-term Safety and Efficacy Studies (1) Study Drug Findings References REVEAL Natalizumab vs Fingolimod Natalizumab superior Butzkeuven H et al. ECTRIMS 2017; Paris, France. Abstract P791. LONGTERMS Fingolimod Established safety and sustained efficacy over 10 years TESMO & TOWER Teriflunomide Abortions and malformations similar to general population Low-grade lymphopenia infrequent TOPAZ Alemtuzumab Reported on safety and efficacy at 7 years Listeria meningitis (0.25%) Cohen J et al. ECTRIMS 2017; Paris, France. Abstract P1879. Comi G et al. ECTRIMS 2017; Paris, France. Abstract 742. Vukusic S et al. ECTRIMS 2017; Paris, France. Abstract 205. Singer BA et al. ECTRIMS 2017; Paris, France. Abstract P736. Coles AJ et al. ECTRIMS 2017; Paris, France. Abstract P1188. Scolding N et al. ECTRIMS 2017; Paris, France. Abstract Rockpointe Page 14

15 Long-term Safety and Efficacy Studies (2) Study Drug Findings References EXTEND Daclizumab Sustained efficacy over 6 years. Recently withdrawn from market Kappos L et al. ECTRIMS 2017; Paris, France. Abstract 731. Cohan S et al. ECTRIMS 2017; Paris, France. Abstract 206. OPERA I & II Ocrelizumab Reduced progression by 36% relative to IFNB-1a at 96 weeks CLARITY extension SUNBEAM & RADIANCE Cladribine Ozanimod Lymphopenia recovers after 1 year 42% achieve NEDA Superior to IFNB-1a ARR 38%-48% No 2 nd degree AV block Kappos L et al. ECTRIMS 2017; Paris, France. Abstract P654. Giovannoni G et al. ECTRIMS 2017; Paris, France. Abstract P1143. Soelberg-Sorensen P et al. ECTRIMS 2017; Paris, France. Abstract P655. Cook S et al. ECTRIMS 2017; Paris, France. Abstract P666. Comi G et al. ECTRIMS 2017; Paris, France. Abstract 232. Arnold DL et al. ECTRIMS 2017; Paris, France. Abstract P1857. Cohen JA et al. ECTRIMS 2017; Paris, France. Abstract 280. Arnold DL et al. ECTRIMS 2017; Paris, France. Abstract P1857. Making Treatment Decisions Considering the Benefits and Risks Evidence-based approach MOA Response Physician experience Safety Treatment decisions Patient preference Cost Tolerability Convenience Monitoring Pregnancy issues 2018 Rockpointe Page 15

16 The Treatment Scale Benefit Risk Clinical Prognostic Factors Favorable Isolated sensory symptoms Complete recovery from first attack Long interval between attacks Low MRI-lesion load Negative CSF OCB Unfavorable Older male Motor, brain stem, and SC involvement High relapse rate in 2-5 years after onset High MRI-lesion load Positive CSF OCB CSF = cerebral spinal fluid; OCB = oligoclonal band; SC = spinal cord Montalban X. Presented at: ECTRIMS 2013, Copenhagen, Denmark; October 2-5, 2013 (Abstract #94) Rockpointe Page 16

17 Prognosis: Initial MRI T2 lesion numbers Median EDSS at 20 years = 6 for >10 T2 lesions 3 or 4 Barkhof criteria moderate correlation with EDSS at 5 years % patients EDSS > 3 EDSS # of brain lesions EDSS = Expanded Disability Status Scale; MRI = magnetic resonance imaging Fisniku LK. Brain. 2008;131: Choosing Therapy Aggressive Disease? Yes No JCV Ab + JCV Ab - Safest Pregnancy Noninjectable Ocrelizumab Alemtuzumab* Fingolimod DMF? Natalizumab IFN GA GA Teriflunomide DMF Insurance?Fingolimod?Natalizumab Ab = antibody; DMF = dimethyl fumarate; GA = glatiramer acetate; INF = interferon; JCV = John Cunningham virus Image courtesy of Aaron Miller Rockpointe Page 17

18 MS Therapies Natalizumab Dimethyl fumarate Fingolimod Alemtuzumab Rituximab* Ocrelizumab Teriflunomide * Denotes off-label use. PML = progressive multifocal leukoencephalopathy Mills EA et al. Front Immunol. 2018;9:138. JCV Antibody Status and Risk for PML JCV antibody status Negative <1/1,000 Calculation based on 2 cases of JCV antibody negative PML in patients exposed for at least 1 month of therapy as of September 3, 2013 Positive Natalizumab exposure Index Result 0.9 PML risk estimate per 1000 pts (No prior IS use) Index Result 1.1 Index Result 1.3 Index Result 1.5 Index Result >1.5 Prior IS use 1-24 months 0.1 (0-0.41) 0.1 (0-0.34) 0.1 ( ) 0.1 ( ) 1.0 ( ) 1/1, months 0.3 ( ) 0.7 ( ) 1.0 ( ) 1.2 ( ) 8.1 ( ) 13/1, months 0.4 (0-0.41) 0.7 ( ) 1.2 ( ) 1.3 ( ) 8.5 ( ) 9/1,000 IS = immunosuppressant; JCV = John Cunningham virus; PML = progressive multifocal leukoencephalopathy Natalizumab Prescribing Information Rockpointe Page 18

19 PML Management Strategies Plasma exchange (PLEX) Switching from natalizumab to alternate DMTs with lower PML risk No PML observed in patients after switching from natalizumab to alemtuzumab, fingolimod, or rituximab Clifford D. ECTRIMS 2017; Paris, France. Abstract 202. Criteria for Switching Therapy Relapse rates of either 1 per year or unchanged from pretreatment rates Incomplete recovery from multiple attacks Evolution of polyregional neurologic involvement Recurrent brainstem or spinal-cord lesions Cumulative loss of neurologic function sufficient to disrupt daily activities Intolerability Pardo G et al. Mult Scler. 2017;264: Rockpointe Page 19

20 Concerns With Switching Therapies Concerns about ongoing risk of PML after natalizumab in JC virus antibody + patients Concerns about need for washout period Concerns about lymphopenia Concerns about post-natalizumab rebound JCV = John Cunningham virus; PML = progressive multifocal leukoencephalopathy ECTRIMS-EAN Clinical Practice Guideline on Pharmacological Management of MS Treatment Initiation IFN or GA for patients with CIS or abnormal MRI who do not fulfill MS criteria Early treatment initiation with DMTs in active RRMS Monitoring Treatment Response Baseline and follow-up brain MRI Measurement of new or enlarging T2 lesions supplemented by GdE lesions CIS = clinically isolated syndrome; ECTRIMS-EAN = European Committee for Treatment and Research in Multiple Sclerosis-European Academy of Neurology; DMT = disease-modifying therapy; GA = glatiramer acetate; GdE = gadolinium-enhanced; INF = interferon; MRI = magnetic resonance imaging; Montalban X et al. Mult Scler. 2018;24: Monitoring Treatment Safety Brain MRI (frequency adjusted based on low- or high-risk PML Switching/Stopping Considerations Offer more efficacious drug to patients progressing on IFN or GA Continue DMT if patient is stable with no safety or tolerability issues Pregnancy Advise women of childbearing age that DMTs (except GA 20 mg/ml) are not recommended during pregnancy 2018 Rockpointe Page 20

21 Incorporating Biomarkers and Risk Factors into MS Management Case Presentation A 25-year-old white female was diagnosed with MS 2 years earlier when she presented with optic neuritis and numbness below the mid-thoracic area. She was placed on interferon-beta 1a IM weekly injections. She continues to have relapses and worsening symptoms Rockpointe Page 21

22 Current MS Biomarkers in Clinical Use Biomarker Neutralizing antibody to IFN-B JCV assay Anti-natalizumab Ab CD19 expression on B-cells CSF oligoclonal IgG bands Aquaporin-4 Ab Varicella Ab Clinical Utility Unresponsiveness PML risk with natalizumab Unresponsiveness Rituximab response MS Diagnosis/Prognosis Neuromyelitis optica Risk of Varicella with fingolimod Ab = antibody; CSF = cerebral spinal fluid; INF = interferon; JCV = John Cunningham virus Coyle PK. Mult Scler Int. 2017;2017: Case (continued) Follow-up MRI showed 2 non-enhancing brain T2 lesions and a new enhancing spinal cord lesion between T1 and T4 Serum NMO Ab titer was elevated 2018 Rockpointe Page 22

23 Neuromyelitis Optica Inflammatory demyelination of the optic nerves and spinal cord Characterized by a specific IgG antibody marker (NMO antibody) Target antigen is aquaporin-4, a water channel abundant in the CNS Role of NMO Ab in pathogenesis remains uncertain Pittock SJ. Semin Neurol. 2008;28: Lennon VA et al. Lancet. 2004;364: Anti-MOG Antibodies Are Present in a Subgroup of Patients with a Neuromyelitis Optica Phenotype anti-mog = anti-myelin oligodendrocyte glycoprotein; NMO = neuromyelitis optica; AQP4 = aquaporin-4 Probstel AK et al. J Neuroinflammation. 2015;12: Rockpointe Page 23

24 NMO Pre- and Post-treatment Median Annualized Relapse Rates Pre- and Post-Tx Relapse Rates Change in EDSS with Treatment Pre- and post-treatment median annualized relapse rates (ARR). The median ARR decreased from 1.17 to 0.25 on rituximab (P<0.01), 0.92 to 0.56 on azathioprine (P=0.475), 1.06 to 0.39 on mycophenolate (P<0.05), and 1.30 to 0.92 on cyclophosphamide (P=0.021). EDSS = Expanded Disability Status Scale; NMO = neuromyelitis optica Torres J et al. J Neurol Sci. 2015;351: Optimizing Patient Engagement and Shared Decision-making Machteld Hillen, MD 2018 Rockpointe Page 24

25 Patient Engagement Promotes... Improved clinical outcomes (treatment adherence, faster recovery, and reduced mortality) Reduced healthcare consumption (improved health service efficiency, fewer diagnostic tests and referrals, decreased use of health services, lower annual charges) Improved service quality (improved communication and health literacy, greater confidence in treatment decisions, decreased malpractice claims, higher staff retention rates, improved patient satisfaction, reduced patient-physician discordance) Rieckmann P et al. Mult Scler Relat Disord. 2015;4: Where We Stand At Present About 60%-65% of patients with MS are adherent with treatment (mostly defined as 80% of days covered) Poor compliance leads to greater healthcare costs (more clinic visits and hospitalizations) Poor compliance may influence long-term disability Burks J et al. Clinicoecon Outcomes Res. 2017;9: Tan H et al. Adv Ther. 2011;28: Locklear J et al. Neurology. 2015;84(supp 14). Gerber B et al. Mult Scler Relat Disord. 2017;18: Rockpointe Page 25

26 Ways to Achieve Patient Engagement Establishment of an effective, caring, and mutually respectful patient physician relationship Shared decision-making (91% of MS patients prefer this) Provide access to credible sources of accurate information Prioritize patient-reported outcomes: increasing the importance placed on QoL and patient concerns Promote patient empowerment through a sense of responsibility Rieckmann P et al. Mult Scler Relat Disord. 2015;4: Colligan E et al. Mult Scler. 2017;23: Shared Decision-making HCP incorporates the patient s values and goals about their care, exploring their life experiences, psychosocial circumstances, and health status HCP then has a discussion of all evidence-based treatment options that are in line with the patient s goals, including the option not to treat, when appropriate HCP partners with the patient to make a decision that is consistent with the patient s personal situation Colligan E et al. Mult Scler. 2017;23: Rockpointe Page 26

27 How to Promote Shared Decision-making Educational programs and information aids Shared Decision-making Tools Text, video, or web-based Colligan E et al. Mult Scler. 2017;23: Benefits of Shared Decision-making Tools Promotes patient autonomy, patient education, and patientcentered care Increase patient s knowledge and perception of risk Patients select options that are congruent with their values Decision aids reduce decisional conflict Increase in patient satisfaction (not proven in MS)? Cost effectiveness (not studied in MS) Colligan E et al. Mult Scler. 2017;23: Rockpointe Page 27

28 Limits of Shared Decision-making Tools Not shown to benefit adherence to therapy Not shown to improve outcomes Decision aids added some time to a patient visit (mean 2.55 minutes longer) Not generalizable to patients who are illiterate or speak a different language Insurance industry in the US determines to a large extent a patient s options for treatment Colligan E et al. Mult Scler. 2017;23: Decision Points in the Course of MS that Lend Themselves to Shared Decision-making Whether to take steroids for an acute relapse Which immunotherapy drug to take, if any Whether to initiate disease-modifying drugs (DMDs) early in the disease course Whether to have a child after being diagnosed with MS 2018 Rockpointe Page 28

29 Examples of Decision Aids Patient Engagement and Shared Decision-making from the Patient Perspective Alina Ahsan Community Planner Health Union 2018 Rockpointe Page 29

30 Barriers to Patient Engagement Health Union s Multiple Sclerosis In America survey showed that 25.8% of RRMS respondents (n= 3,559) rarely or never engage with their HCPs when experiencing a relapse 57.9% did not consider their relapse to be severe enough 30.9% felt their HCPs were unhelpful (during past relapses) or did not tell them they should contact them if they experienced a relapse 25.6% felt treatment doesn t work well/can t tolerate 24% prefer to manage alone Nazareth T et al. Institutions: Mallinckrodt Pharmaceuticals, Bedminster, NJ; Health Union, Philadelphia, PA. Presented at: 7 th Joint ECTRIMS-ACTRIMS Meeting October 25-28, 2017; Paris, France. P Rockpointe Page 30

31 Encouraging Adherence through Engagement (1) For SDM to occur, patients need to be informed and involved (to the level of their choosing) Even when HCPs provide all of the information and options, patients may not be given time to process the information After a conversation with their HCPs, patients forget 40%-80% of the information discussed NEDA is often the goal for HCPs treating MS; for patients, stable disease does not always mean symptom-free Focusing on patients goals for their treatment (often managing symptoms and fewer relapses) can be the key to improved patient engagement and adherence HCP = healthcare provider; NEDA = no evidence of disease activity Kessels RP. J R Soc Med. 2003;96: Encouraging Adherence through Engagement (2) HCP Strategies for Shared Decision-making 1. Explore all options 2. Identify biases and work to minimize them in patient interactions 3. Acknowledge and reveal experience with various procedures and treatments 4. Respect what matters most to the patient, including the risks and benefits associated with a variety of options HCP = healthcare provider; NEDA = no evidence of disease activity Kessels RP. J R Soc Med. 2003;96: Rockpointe Page 31

32 Online Communities as Sources for Accurate Information Directing patients towards online communities can empower them to connect with other patients like themselves, share experiences, and hear from experts and advocates Offering them curated articles that explain common questions and misconceptions in a digestible form can help them more easily understand their diagnoses and options g-with-ms/the-neurologicalexam-explained/ g-with-ms/lets-addresselephant-room-depression/ g-with-ms/some-of-the-weirderms-symptoms/ g-with-ms/multiple-sclerosis- 101-understanding-immunesystem/ Perspectives from the Patient Laura Kolaczkowski 2018 Rockpointe Page 32

33 Question & Answer Session Suhayl Dhib-Jalbut, MD Rutgers NJ Medical School Newark, NJ Rutgers Robert Wood Johnson Medical School New Brunswick, NJ Machteld E. Hillen, MD Rutgers NJ Medical School Newark, NJ Alina Ahsan Health Union, LLC MultipleSclerosis.net Philadelphia, PA Laura Kolaczkowski MultipleSclerosis.net Dayton, OH Thank you for joining us today! Please remember to complete the EVALUATION on the ipad. Your participation will help shape future CME activities Rockpointe Page 33