Is the Grass Really Greener with New Oral Multiple Sclerosis Treatments? A Clinical Debate

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2 Is the Grass Really Greener with New Oral Multiple Sclerosis Treatments? A Clinical Debate Elizabeth Sebranek Evans, PharmD, BCPS, CGP Alana Whittaker, PharmD, BCPS Roseman University of Health Sciences 10 October 2015

3 Disclosures Dr. Elizabeth Sebranek Evans is a consultant for VRx Dr. Alana Whittaker has nothing to disclose Off-label medication use will be discussed in this presentation

4 Learning Objectives Review of the pathophysiology and clinical presentation of multiple sclerosis (MS) Compare and contrast the efficacy of new oral agents for MS versus traditional injectable therapies for MS Compare and contrast the safety of new oral agents for MS versus traditional injectable therapies for MS Discuss potential treatment options for MS in the pipeline

5 Overview of MS Greater than 2.3 million people worldwide affected by disease Most patients diagnosed between ages of 20 and 50 Leading cause of disability in young adults At least 2-3 times more common in women than men More common in areas furthest away from equator International Progressive MS Alliance

6 Pathophysiology Hypothesized the blood-brain barrier becomes compromised Lymphocytes recognize myelin antigen to trigger a cascade of inflammatory events Results in inflammatory, demyelinating lesions Lesions develop in white matter and target the myelin sheath and oligodendrocytes Frohman EM, et al. New Engl J Med. 2006;354(9):

7 Pathophysiology Steinman L. Nat Review Immunol 2009 Jun;9:440-7.

8 Clinical Presentation of MS Clinical presentation and course of disease varies

9 Clinical Presentation of MS Daroff: Bradley's Neurology in Clinical Practice, 6th ed.

10 Disability and Death from MS: EDSS Scale Adapted from Kurtzke JF. Neurology. 1983; 33:

11 Audience Response Which type of MS is characterized by relapses with partial to full recovery between episodes? A. Primary progressive (PPMS) B. Secondary progressive (SPMS) C. Progressive relapsing (PRMS) D. Relapsing-remitting (RRMS)

12 Principles of Treatment of MS Difficult to treat due to wide spectrum of disease presentation No evidence-based treatment guidelines regarding choice of DMT Aim of DMT is to reduce progression or severity of disease, no cure available Start treatment as early as possible Patients should be screened for development of organ complications Tavazzi E, et al. CMAJ. 2014;186(11): DMT = disease-modifying therapy

13 Selected FDA-Approved Treatment Options for MS Traditional Therapies Beta interferon Interferon ß-1a (Avonex ) Interferon ß-1a (Rebif ) Interferon ß-1b (Betaseron ) Glatiramer (Copaxone ) Natalizumab (Tysabri ) Newer Agents Fingolimod (Gilenya ) Teriflunomide (Aubagio ) Dimethyl fumarate (Tecfidera )

14 Additional Treatment Options for MS FDA Approved Therapies Mitoxantrone (Novantrone ) Alemtuzumab (Lemtrada ) Peginterferon ß-1a (Plegridy ) Non-FDA Approved Agents Azathioprine Cyclophosphamide

15 Role of Medications in MS Treatment Traditional Agents Newer Agents Medication Interferon ß-1a (Avonex ) Interferon ß-1a (Rebif ) Interferon ß-1b (Betaseron ) Indication Relapsing forms of MS Slows progression Glatiramer acetate (Copaxone ) Relapsing remitting MS Reduces lesions Natalizumab (Tysabri ) Relapsing remitting MS Intolerance to other agents Disease activity while on other agents Fingolimod (Gilenya ) Relapsing forms of MS Teriflunomide (Aubagio ) Relapsing forms of MS Dimethyl fumarate (Tecfidera ) Relapsing forms of MS Frohman EM, et al. New Engl J Med. 2006;354(9): Gilenya package insert. Aubagio package insert. Tecfidera package insert.

16 First Proposition Traditional therapies for MS are better than newer oral therapies for MS regarding efficacy.

17 Efficacy: Interferon ß-1a Characteristic Study Design PRISMS Patient Population 2 year, double-blind, RCT N = 560 Details Relapsing-remitting MS 22 centers in 9 countries Median age = 35, 69% female Intervention IFNß-1a 22 mcg TIW versus IFNß-1a 44 mcg TIW vs. placebo Results Mean relapses: Placebo 2.56, IFNß-1a 22 mcg 1.82, IFNß-1a 44 mcg 1.73 % reduction versus placebo: IFNß-1a 22 mcg (27, 95% CI 14-39, p<0.005) IFNß-1a 44 mcg (33, 95% CI 21-44, p<0.005) No differences in progression of disability with IFNß-1a groups, but progression seen in placebo group Comments PRISMS Study Group. Lancet. 1998;352(7): Superior efficacy of IFNß-1a over placebo RCT = randomized controlled trial IFN = interferon

18 Efficacy: Interferon ß-1a (Long Term) 15 year follow-up data Analysis of 122 living patients Patients were allowed to use other DMTs regarding choice of DMT Results show that patients who are currently taking IFNß-1a had lower EDSS scores, a smaller mean increase in EDSS scores, and had a better QOL No new safety concerns identified Bermel RA, et al. Multiple Sclerosis. 2010;16(5): DMT = disease-modifying therapy QOL = quality of life

19 Efficacy: Peginterferon ß-1a Characteristic Study Design ADVANCE Patient Population 48 week, double-blind, RCT N = 1936 Relapsing-remitting MS 183 centers in 26 countries Mean age = 36, 71% female Details Intervention PEGIFNß-1a 125 mcg q 2 wks versus PEGIFNß-1a 125 mcg 4 wks versus placebo Results Comments Relapse rate: PEGIFNβ-1a 125 mcg q 2 wks (0.256, 95% CI , p=0.007) PEGIFNβ-1a 125 mcg q 4 wks (0.288, 95% CI , p=0.0114) Placebo (0.397, 95% CI ) No differences in progression of disability with IFNß-1a groups, but progression seen in placebo group Superior efficacy of PEGIFNß-1a over placebo Calabresi PAA, et al. Lancet Neurol. 2014;13: RCT = randomized controlled trial PEGIFN = pegylated interferon

20 Efficacy: Interferon β-1b Characteristic Study Design IFNB Study Group Patient Population 4 year, double-blind, RCT N = 372 Details Relapsing-remitting MS 22 centers in 9 countries Median age = 35, 69% female Intervention IFNß-1b 8 million units versus 16 million units versus placebo Results Comments Annual exacerbations rate: IFNß-1b 8 million units (0.78, 95% CI ) IFNß-1b 16 million units (0.96, 95% CI ) Placebo (1.12, 95% CI ) No difference in EDSS scores between groups Superior efficacy of IFNß-1b over placebo IFNB MS Study Group. Neurology. 1995;45: RCT = randomized controlled trial IFN = interferon

21 Efficacy: Interferon ß-1a (Long Term) Five year follow-up data 261 patients with first event suggestive of MS and at least 2 clinically silent lesions in early treatment (median LOF was 5 years) 157 patients in delayed treatment group (median LOF was 1 year 11 months) Results show that early intervention reduced risk of diagnosis of MS, but no difference in EDSS scores No new safety concerns identified Kappos L, et al. Lancet Neurol. 2009;8): LOF = length of follow-up

22 Efficacy: Interferon ß-1a (Long Term) 16 year follow-up data Analysis of 260 living patients Patients were allowed to use other DMT Results show that patients who received IFNß 1b during the initial study period had a better chance of survival and lower numbers who reached an EDSS score of 6 No new safety concerns identified Ebers GC, et al. J Neurol Neurosurg Psychiatry. 2010;81: DMT = disease-modifying therapy

23 Efficacy: Glatiramer Characteristic Study Design Patient Population Intervention Results Comments Johnson KP et al. Neurology. 1995;45: years, double-blind, RCT N = 251 Relapsing-remitting MS 11 centers in USA Average age = 35, 73% female Details Glatiramer 20 mg SQ daily versus placebo Mean relapse rate: Glatiramer 20 mg (1.19 ± 0.13) Placebo (1.68 ± 0.13) 29% reduction in relapse rate (p=0.007) Glatiramer improved disability scores while placebo worsened disability scores Superior efficacy of glatiramer over placebo for relapse rates and disability scores RCT = randomized controlled trial

24 Efficacy: Glatiramer (Long Term) 15 year follow-up data Analysis of 231 patients who had only used glatiramer Withdrawn (131 patients) and ongoing (100 patients) cohorts Results show that the ongoing cohort had a 0.6±2.0 and the withdrawn cohort had a 1.0± 1.7 change in EDSS from baseline No new safety concerns identified Ford C, et al. Multiple Sclerosis. 2010; 16(3): DMT = disease-modifying therapy

25 Efficacy: Natalizumab Characteristic Study Design Patient Population 12-month, double-blind, RCT N = 942 Relapsing-remitting MS 99 centers worldwide Average age = 36, 70% female Details Intervention Natalizumab 300 mg IV versus placebo (2:1) Results Comments Annualized relapse rate: Natalizumab 300 mg (0.23, 95% CI , p<0.001) Placebo (0.73, 95% CI ) There was a significant difference in sustained progression of disability favoring the natalizumab group Superior efficacy of natalizumab over placebo Polman CH, et al. New Engl J Med. 2006;354(9): RCT = randomized controlled trial

26 Efficacy: Natalizumab (Long Term) 240 week follow-up data Analysis of 1,094 patients who had previously used natalizumab in other trials and now natalizumab monotherapy Results show that EDSS scores were lower in the group who started natalizumab (2.79) versus the placebo (3.19) group at 240 weeks (p = 0.024), but the placebo group patients had higher EDSS scores at baseline No new safety concerns identified O Connor P, et al. Neurology. 2014; 83(1):78-86.

27 First Proposition Rebuttal Second Proposition Newer oral therapies for MS are better than traditional therapies for MS regarding efficacy.

28 Efficacy Issues with Traditional MS Agents All trials for first line agents conducted against placebo Long-term studies not convincing Only a small subset of original patients followed Heterogeneity of patients Patients allowed to take other DMTs Minimal improvements in EDSS scores Patients in some trials may have had milder forms of the disease Natalizumab, agent with the best efficacy, is not considered a first list line agent due to side effects Bermel RA, et al. Multiple Sclerosis. 2010;16(5): Kappos L, et al. Lancet Neurol. 2009;8): O Connor P, et al. Neurology. 2014; 83(1): Ford C, et al. Multiple Sclerosis. 2010; 16(3): Ebers GC, et al. J Neurol Neurosurg Psychiatry 2010;81:

29 Efficacy: Fingolimod Characteristic Study Design FREEDOMS trial Patient Population Intervention Results Comments Kappos L et al. New Engl J Med. 2010;362: month, double-blind RCT N = 1272 Details Relapsing-remitting MS 138 centers in 22 countries Age 18-55, average age = 37; % female Fingolimod 1.25 mg or 0.5 mg versus placebo Primary endpoint of relapse rate: Fingolimod 0.5 mg (0.18, 95% CI , p<0.001) Placebo (0.40, 95% CI ) Secondary endpoint of absence of disability progression Fingolimod 0.5 mg (82.3%, 95% CI %, p=0.03) Placebo (75.9%, 95% CI %, p=0.02) Both doses improved relapse rate by 54-60%, risk of disability progression, and end points on MRI versus placebo MRI = magnetic resonance imaging RCT = randomized controlled trial

30 Efficacy: Fingolimod Characteristic Study Design TRANSFORMS trial Patient Population Intervention Results Comments Details 12-month, double-blind, double-dummy RCT N = 1153 Relapsing-remitting MS 172 centers in 18 countries Age 18-55, average age = 36; % female Fingolimod 1.25 mg or 0.5 mg versus interferon ß1-a 30 QW Relapse rate: Fingolimod 0.5 mg (0.16, 95% CI , p<0.001) Interferon (0.33, 95% CI ) No significant differences in progression of disability Superior efficacy of oral fingolimod over intramuscular interferon ß-1a Cohen JA, et al. New Engl J Med. 2010;362: RCT = randomized controlled trial

31 Efficacy: Teriflunomide Characteristic Study Design TEMSO trial Patient Population Intervention Results Comments 108 week, double-blind RCT N = 1086 Details Relapsing remitting MS, subgroup with secondary progressive or progressive relapsing MS; EDSS 5.5 or lower 127 centers in 21 countries Age 18-55; 70% female Teriflunomide 7 mg or 14 mg vs. placebo Reduces annualized relapse rate 0.54 for placebo vs for teriflunomide with relative risk reductions of 31.2% and 31.5%, (P < 0.001) Disability progression 27.3% placebo, 21.7% teriflunomide 7 mg (p = 0.08), 20.2% teriflunomide 14 mg (p = 0.03) Significantly reduced annualized relapse rate, disability (14 mg dose), and MRI evidence of disease activity O Connor P, et al. New Engl J Med. 2011;365: RCT = randomized controlled trial

32 Efficacy: Teriflunomide Characteristic Study Design TOWER trial Patient Population Intervention Results Comments 48 week, double-blind RCT N = 1169 Details Relapsing remitting MS, EDSS 5.5 or lower 189 centers in 26 countries Age 18-55; 70% female Teriflunomide 7 mg or 14 mg vs. placebo Reduces annualized relapse rate 0.5 for placebo (95% CI ) vs for teriflunomide 7 mg (95% CI ; p=0.0183) vs for teriflunomide 14 mg (95% CI ; p=0.0001) Disability progression Teriflunomide 7 mg HR 0.95 (95% CI ); teriflunomide 14 mg HR 0.68 (95% CI ) Teriflunomide 14 mg associated with lower relapse rate and less disability accumulation compared to placebo Confavreux C, et al. Lancet Neurol. 2014;13(3): RCT = randomized controlled trial

33 Efficacy: Teriflunomide Characteristic Study Design Patient Population Intervention Results Comments Details 48 week, multicenter, rater-blinded RCT N = 324 Relapsing remitting MS, EDSS 5.5 or lower Age 18 (average age = 36); % female; 100% Caucasian Teriflunomide 7 mg or 14 mg vs. IFNß-1a 44 mcg Primary endpoint: Time to failure (first relapse or permanent treatment discontinuation) No difference between either dose of teriflunomide (36% with 7 mg; 33% with 14 mg) and IFNß-1a (37%) Secondary endpoint: Annualized relapse rate (ARR) No difference between IFNß-1a and teriflunomide 14 mg (0.22 vs. 0.26, p=0.06) Higher ARR with teriflunomide 7 mg vs IFNß-1a (0.41, p=0.03) Larger patient population, longer duration and MRI outcomes needed Dose-response relationship with teriflunomide confirms earlier trials Vermersch P, et al. MSJ. 2014;20(6): RCT = randomized controlled trial; IFN = interferon MRI = magnetic resonance imaging

34 Efficacy: Dimethyl fumarate Characteristic Study Design Patient Population Intervention Results Comments 48 weeks, placebo-controlled RCT N = 1234 Details Relapsing remitting MS, EDSS 5.0 or lower 198 centers in 28 countries Age 18-56, average age 38; 72-75% female BG mg BID or TID vs. placebo Primary endpoint: Proportion of patients with relapse by 2 year 46% for placebo vs. 27% BG-12 BID (p < ) Secondary endpoints: Disability and MRI lesions Significantly reduced the progression of disability versus placebo (16% vs. 27%, p=0.005) and mean number of new active MRI lesions (p<0.001) Both doses of BG-12 reduced % patients with relapse, annualized relapse rate, disability progression, number of lesions on MRI Gold R, et al. New Engl J Med. 2012;367: BG-12 = dimethyl fumarate RCT = randomized controlled trial

35 Efficacy: Dimethyl fumarate Characteristic Study Design CONFIRM trial Patient Population Intervention Results Comments 96 weeks, placebo-controlled RCT N = 1417 Details Relapsing remitting MS, EDSS 5.0 or lower 127 centers in 21 countries Age 18-55, average age 37; 68-71% female BG mg BID or TID vs. glatiramer 20 mg vs. placebo Reduces annualized relapse rate 0.40 for placebo vs BG-12 BID (p < ) vs glatiramer (p<0.01) Disability progression not significant Both dosing regimens of BG-12 and glatiramer significantly reduced lesions (p<0.001) BG-12 and glatiramer significantly reduces relapse rates and neuroradiologic outcomes relative to placebo Fox RJ, et al. New Engl J Med. 2012;367: BG-12 = dimethyl fumarate RCT = randomized controlled trial

36 Second Proposition Rebuttal Traditional therapies for MS are better than newer oral therapies for MS regarding efficacy.

37 Efficacy Issues with Newer Oral MS Agents No long-term studies are available for any agent Many similar limitations in trial design to traditional agents Fingolimod Teriflunomide Dimethyl fumarate No trials greater than 2 years Progression of disability not demonstrated to be superior to traditional agents Kappos L et al. New Engl J Med. 2010;362: Cohen JA, et al. New Engl J Med. 2010;362: Confavreux P, et al. Lancet Neurol. 2014; 3: O Connor P, et al. New Engl J Med. 2011;365: mg dose failed to demonstrate disability progression in both the TEMSO and TOWER trials Relapse rate with 7 mg dose higher than INFß Vermersch P, et al. MSJ. 2014;20(6): Gold R, et al. New Engl J Med. 2012;367: Fox RJ, et al. New Engl J Med. 2012;367: Superiority over glatiramer not demonstrated Proof of efficacy and progression of disability not demonstrated to be superior to traditional agents

38 Audience Response Which therapy do you think is better for MS regarding efficacy? A. Traditional therapies B. Newer oral therapies C. Both therapies are equally effective

39 First Proposition Traditional therapies for MS are better than newer oral therapies for MS regarding safety.

40 Safety: Interferon β -1a Common Safety Issues Injection site reactions (71%) Flu like symptoms (69%) Depression (30-33%) Increased LFTs (24-30%) Serious Safety Issues Leukopenia (27-35%) Injection site necrosis (< 1%) Cardiomyopathy Avonex package insert. Rebif package insert. PRISMS Study Group. Lancet. 1998;352(7):

41 Copaxone package insert. Johnson KP et al. Neurology. 1995;45: Safety: Glatiramer Common Safety Issues Injection site reactions (60%) Anxiety (13%) Chest pain (2-13%) Serious Safety Issues Dyspnea (3-14%) Injection site necrosis (< 1%)

42 Safety: Natalizumab Common Safety Issues Flu like symptoms (< 38%) Infections (21%) Depression (19%) Serious Safety Issues Tysabri package insert. TYSABRI TOUCH Prescribing Program. Polman CH, et al. New Engl J Med. 2006;354(9): PML ( %) Anaphylaxis (< 1%) Cancer (<1%) Natalizumab has a REMS program PML = progressive multifocal encephalopathy REMS = Risk Evaluations and Mitigation Strategies

43 First Proposition Rebuttal Second Proposition Newer oral therapies for MS are better than traditional therapies for MS regarding safety.

44 Safety Issues with Traditional Agents for MS Over % of patients taking interferons discontinue drug for reasons other than drug failure Flu-like symptoms Psychiatric issues Injection-site reactions Increase in muscle spasticity at beginning of therapy Oral agents for MS are advantageous for patients who would otherwise be untreated Tavazzi E, et al. CMAJ. 2014;186(11):

45 Safety Issues with Traditional Agents for MS Natalizumab Can cause PML PML can result in short-term disability, permanent disability, or death Risk for PML increases for patients previously treated with immunosuppressive therapy Baseline and routine CBC, LFTs, JCV serology, and brain MRI Natalizumab Exposure No Prior Immunosuppressant Use Anti-JCV Antibody Positive Prior Immunosuppressant Use 1-24 Months < 1 / / Months 5 / / 1000 Weissert R. J Neuroimmunol. 2011;231: Bloomgren G, et al. New Engl J Med. 2012;366: Tavazzi E, et al. Clin Microbiol Infect. 2011;17: PML = progressive multifocal encephalopathy JCV = John Cunningham Virus REMS = Risk Evaluations and Mitigation Strategies

46 Safety: Fingolimod Common Safety Issues Serious Safety Issues Headache (25%) Backache (12%) Diarrhea (12%) Increased LFTs (14%) Severe lymphocytopenia (18%) Atrioventricular block (3.7%) Fingolimod has a REMS program Gilenya package insert. Cohen JA, et al. N Engl J Med. 2010;262: REMS = Risk Evaluations and Mitigation Strategies Kappos L, et al. N Engl J Med. 2010;362: Fingolimod risk evaluation and mitigation strategy (REMS). [Internet]. Atlanta (GA): Food and Drug Administration; [updated 2015 May; cited 2015 Aug 31]. Available from:

47 Safety: Teriflunomide Common Safety Issues Serious Safety Issues Headache (19-22%) Alopecia (10-13%) Hypophosphatemia (5-18%) Diarrhea (15-18%) Nausea (9-14%) Contact dermatitis (5-8%) Increased hepatic transaminases Teratogenicity Neutropenia Influenza Aubagio package insert. O Connor P, et al. New Engl J Med. 2011;365: Confavreux C, et al. Lancet Neurol 2014;13:

48 Safety: Dimethyl fumarate Less monitoring and side effects than interferons, natalizumab, fingolimod, and teriflunomide Common Safety Issues Flushing (40%) Abdominal pain (18%) Diarrhea (14%) Nausea (12%) Contact dermatitis (5-8%) Serious Safety Issues Leukopenia or lymphopenia (60%) Tecfidera package insert. Gold R, et al. New Engl J Med. 2012;367: Fox RJ, et al. New Engl J Med. 2012;367:

49 Second Proposition Rebuttal Traditional therapies for MS are better than newer oral therapies for MS regarding safety.

50 Safety Concerns with Newer Oral MS Therapies Fingolimod Risk of bradycardia within 6 hours of first dose; inconvenient and expensive initiation of therapy Risk for macular edema Reports of death due to varicella requires VZV vaccination in nonimmune patients New reports of PML in 2 patients with no prior exposure to immunosuppressants Wingerchuck DM, et al. Mayo Clin Proc. 2014;89(2): Gilenya (fingolimod): Drug Safety Communication - FDA Warns About Cases of Rare Brain Infection. [Internet]. Atlanta (GA): Food and Drug Administration; [updated 2015 Aug 4; cited 2015 Aug 31]. Available from:

51 Safety Concerns with Newer Oral MS Therapies Teriflunomide Risk of teratogenicity in population most likely to have the disease Monthly LFT checks required Dimethyl fumarate Capsule must be swallowed whole, may be problematic in patients with swallowing difficulties Reports of PML in Europe in patients using similar product for treatment of psoriasis Wingerchuck DM, et al. Mayo Clin Proc. 2014;89(2):

52 Audience Response Which therapy do you think is better for MS regarding safety? A. Traditional therapies B. Newer oral therapies C. Both therapies are equally safe

53 Audience Response Which therapy do you think is better for MS regarding overall? A. Traditional therapies B. Newer oral therapies C. Both are therapies are equal

54 Medication Hartung DM, et al. Neurology. 2015;84(21): Additional Considerations: Cost Increases in MS Treatments Approval Date Cost at Approval Date 2013 Annual Cost Annual Change, % IFNß-1b (Betaseron ) 1993 $11,532 $61, IFNß-1a (Avonex ) 1996 $8732 $62, Glatiramer (Copaxone ) 1996 $8292 $59, IFNß-1a (Rebif ) 2002 $15,262 $66, Natalizumab (Tysabri ) 2004 $25,850 $64, Fingolimod (Gilenya ) 2010 $52,775 $63, Teriflunomide (Aubagio ) 2012 $47,651 $57, Dimethyl fumarate (Tecfidera ) 2013 $57,816 $63,

55 Agents for MS in the Pipeline Laquinomod Similar to linomide, which was halted after cardiovascular events and deaths during phase 3 trials Ocrelizumab Humanized anti-cd20 monoclonal antibody similar to rituximab Daclizumab Monoclonal antibody for CD25 subunit of interleukin 2 receptor Wingerchuck DM, et al. Mayo Clin Proc. 2014;89(2):

56 Agents for MS in the Pipeline Oh J, Calabresi PA. Lancet Neurol. 2013;12:

57 Additional MS Agents in the Pipeline Relapsing-remitting Cholecalciferol Estroprogestins Estriol Guanabenz Lamotrigine Liothyronine Raltegravir RN260 Simvastatin Testosterone 18F-DPA-714 and 18F-FDG rhigm22 Progressive BAF312 Domperidone Estriol Fampridine Idebenone Liothyronine Lipoic acid Masitinib MSS146 Riluzole Rituximab RTL 1000 Sunphenon Testosterone 18F-DPA-714 and 18F-FDG Accessed 31 Aug 2015.

58 Audience Response Do you think a clinical cure for MS is in the pipeline? A. Definitely yes B. Definitely no C. Not sure

59 Summary There is no treatment to reverse course of MS Treatment choice is dictated by clinical presentation, course of disease, and patientspecific considerations Lacking evidence of effective treatments for progressive forms of MS Lacking evidence-based guidelines for selection of initial agent and how to switch therapy All agents have varying degrees of efficacy and safety concerns

60 Is the Grass Really Greener with New Oral Multiple Sclerosis Treatments? A Clinical Debate Elizabeth Sebranek Evans, PharmD, BCPS, CGP Alana Whittaker, PharmD, BCPS Roseman University of Health Sciences 10 October 2015