Timing is Everything: The Importance of Early Intervention in Multiple Sclerosis

Timing is Everything: The Importance of Early Intervention in Multiple Sclerosis Challenge Question: Pathophysiology Which of the following is a correct statement about the pathophysiology of MS and/or its relation to clinical symptoms? A. Transition from relapsing-remitting to secondaryprogressive MS is infrequently accompanied by decreases in brain volume B. Irreversible axonal injury and loss may occur early in MS C. Inflammation and demyelination predominate in later stages of MS D. Axonal loss in MS is almost always accompanied by clinical symptoms

Challenge Question: Diagnosis and Treatment of Clinically- Isolated Syndrome (CIS) (1) Which of the following is true about the McDonald diagnostic criteria for MS? A. The McDonald criteria do not include an objective demonstration of dissemination of lesions in both time and space B. The McDonald criteria include a category for laboratorysupported MS based on cerebrospinal fluid (CSF) oligoclonal bands or elevated IgG C. Magnetic resonance imaging (MRI) criteria are incorporated in the McDonald diagnostic scheme D. The McDonald criteria do not include possible MS Challenge Question: Diagnosis and Treatment of CIS (2) Which of the following is NOT correct concerning pharmacologic treatment of MS? A. Clinical trials to date suggest clinical outcomes are similar with delayed versus immediate treatment of patients with CIS B. BENEFIT is the only study to date showing an effect of treatment on delaying disability progression in the CIS patient population C. In PreCISe, glatiramer acetate reduced risk of clinicallydefinite MS by 45% versus placebo in CIS patients D. The safety/tolerability of interferons (IFNs) in CIS patients is consistent with the profile previously observed in patients with relapsing forms of MS

Challenge Question: Tolerability and Adherence Strategies Which of the following is true concerning tolerability/adherence of disease-modifying drugs (DMDs) in MS? A. Use of analgesics and dose titration schedules have been shown to improve adherence to IFN beta-1b B. Adherence is highest when patients choose their own treatment without physician guidance C. Warming the medication has no impact on injection site reactions D. Autoinjectors are not useful with MS therapies Learning Objectives Describe the value of early intervention in slowing the progression of or conversion to MS Summarize recent clinical trial data with respect to early intervention and clinical outcomes in CIS/MS List approved MS DMDs and their indications Assess the advantages and disadvantages of MS treatments with respect to their efficacy, safety, and tolerability Define nursing and physician interventions to increase the likelihood of initiating and continuing effective, safe, and tolerable MS therapy for patients with new-onset CIS/MS

Performance Goal Counsel patients about the importance of adherence for assuring the best outcomes with MS therapies Faculty Fred D Lublin, MD [chair] Saunders Family Professor of Neurology Corinne Goldsmith Dickinson Center for Multiple Sclerosis Mount Sinai School of Medicine New York, New York Christopher Hughes, MD, PhD Center for Neurosciences, Orthopedics and Spine Dakota Dunes, South Dakota Amy Perrin Ross, APN, MSN, CNRN, MSCN Neuroscience Program Coordinator Loyola University Medical Center Maywood, Illinois

Part 1 The Pathology of MS: Demyelination and Axonal Loss Occur Early and Lead to Permanent Disability Christopher Hughes, MD, PhD Center for Neurosciences, Orthopedics and Spine Dakota Dunes, South Dakota Natural History of MS Measures of brain volume Relapses and impairment MRI burden of disease MRI activity Secondary-Progressive Preclinical Relapsing-Remitting Time NEUROSCIENTIST by Trapp BD et al. Copyright 1999 by Sage Publications Inc. Journals. Reproduced with permission of Sage Publications Inc. Journals in the format electronic usage via Copyright Clearance Center. Adapted from Trapp BD et al. Neuroscientist. 1999;5:48-57.

Nerve Damage and Myelin Loss Exposed axons may be severed This leads to permanent loss of axons (reduced N-acetyl aspartate) Compensation occurs but is eventually exhausted This eventually leads to permanent loss of function Early treatment could prevent this cascade NEUROSCIENTIST by Trapp BD et al. Copyright 1999 by Sage Publications Inc. Journals. Reproduced with permission of Sage Publications Inc. Journals in the format electronic usage via Copyright Clearance Center. Adapted from Trapp BD et al. Neuroscientist. 1999;5:48-57. MS Clinical Trials Relapsing-remitting MS trials showed greater therapeutic benefits than secondary-progressive MS trials = Clinical trials A = Trials in CIS with IM or SC IFN beta-1a, IFN beta-1b 1-3 B = Pivotal trials in relapsing-remitting MS with IM or SC IFN beta-1a, IFN beta-1b, glatiramer acetate 4-7 C = European secondary-progressive trial with IFN beta-1b 8 D = Secondary-progressive trials with IM or SC IFN beta-1a 9,10 E = North American secondary-progressive trial with IFN beta-1b 11 A Relapsing-remitting to secondary-progressive B Relapsing-Remitting C D E Secondary-Progressive Disability threshold Disease stage Time The longer the delay in treatment, the less effective IFNs and glatiramer acetate seem to be. Secondary-progressive MS is the ultimate delay in treatment. 1. Jacobs LD et al. N EnglJ Med.2000;343:898-904. 2. Comi G et al. Lancet. 2001;357:1576-1582. 3. Kappos L et al. Neurology. 2006;67:1242-1249. 4. Jacobs LD et al. Ann Neurol. 1996;39:285-294. 5. PRISMS Study Group. Lancet. 1998;352:1498-1504. 6. IFNβ Multiple Sclerosis Study Group. Neurology. 1993;43:655-661. 7. Johnson KP et al. Neurology. 1995;45:1268-1276. 8. European Study Group on Interferon Beta-1b in Secondary Progressive MS. Lancet. 1998;352:1491-1497. 9. Cohen JA et al. Neurology. 2002;59:679-687. 10. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Neurology. 2001;56:1496-1504. 11. North American Study Group on Interferon Beta-1b in Secondary Progressive MS. Neurology. 2004;63:1788-1795.

Prognosis of Disability 50% of all patients will need assistance in walking within 15 y of the onset of MS 1 3 The exacerbation rate early in the disease course predicts the future progression rate and disability status. According to Weinshenker et al, the median time to reach Expanded Disability Status Scale (EDSS) 6.0 is: <7 y in patients who had 5 attacks in the first y 13 y in those who had 2 4 attacks in the first y 18 y in those who had <2 attacks in the first y Early activity late degeneration (Disconnect) 1. Weinshenker BG et al. Brain. 1989;112 (Pt 1):133 146. 2. Weinshenker BG et al. Brain. 1989;112 (Pt 6):1419 1428. 3. Weinshenker BG et al. Brain. 1991;114 (Pt 2):1045 1056. Clinical Symptoms Underestimate Disease Activity MS may appear to be silent (with no new or worsening visible signs or symptoms) while it is active Silent damage to axons may lead to permanent disability later on Starting effective treatment early may help slow the accumulation of damage Today s axonal loss, tomorrow s clinical symptoms Time Clinical Clinical Clinical symptoms symptoms symptoms Axonal loss Axonal loss Axonal loss Coyle PK, Hartung H-P. Mult Scler. 2002;8:2-9. Narayanan S, et al. J Neurol.2001;248:979-986. Dalton CM et al. J Neurol Neurosurg Psychiatry. 2002;73:141-147.

Conclusions Multiple sclerosis causes both demyelination and neuronal loss Much of the MS disease activity is silent but progressive As the disease progresses, inflammation diminishes and neuronal dropout accelerates Early use of DMDs gives the best chance of altering the course of MS Rechallenge Question: Pathophysiology Which of the following is a correct statement about the pathophysiology of MS and/or its relation to clinical symptoms? A. Transition from relapsing-remitting to secondaryprogressive MS is infrequently accompanied by decreases in brain volume B. Irreversible axonal injury and loss may occur early in MS C. Inflammation and demyelination predominate in later stages of MS D. Axonal loss in MS is almost always accompanied by clinical symptoms

Part 2 Diagnosing and Treating Clinically Isolated Syndrome (CIS) Fred D Lublin, MD Saunders Family Professor of Neurology Corinne Goldsmith Dickinson Center for Multiple Sclerosis Mount Sinai School of Medicine New York, New York Definition of CIS A first neurologic episode, lasting at least 24 hours, which is caused by inflammation/demyelination in one or more sites in the CNS National MS Society Information Sourcebook.

Differential Diagnosis of CIS Stroke/transient ischemic attack (TIA) Neurosyphilis Vasculitis Sjögren s disease Systemic lupus erythematosus (SLE) Neurosarcoidosis Progressive multifocal leukoencephalopathy (PML) Lyme disease McDonald MS Diagnostic Criteria Objective demonstration of dissemination of lesions in both time and space remains essential Neurologic examination MRI and/or evoked potentials MRI is integrated with clinical and other para-clinical diagnostic methods Diagnostic evaluation outcome MS Possible MS Not MS McDonald WI et al. Ann Neurol. 2001;50:121-127.

MRI Criteria for Dissemination in Space and Dissemination in Time for MS McDonald Criteria 2005 Revision Dissemination in Space 3 of the following: 9 T2 lesions or 1 gadolinium (Gd)- enhancing lesion 3 periventricular lesions 1 juxtacortical lesion 1 posterior fossa lesion or spinal-cord lesion A spinal-cord lesion can replace an infratentorial lesion Any number of spinal-cord lesions can be included in total lesion count Dissemination in Time A Gd-enhancing lesion 3 months after CIS onset A new T2 lesion with reference to a baseline scan obtained 30 d after CIS onset Polman CH et al. Ann Neurol. 2005;58:840-846. Available for download at http://www.nationalmssociety.org/download.aspx?id=215. Initial CIS Studies CHAMPS (The Controlled High Risk Avonex MultiPle Sclerosis) Trial Primary end point: Time to dx of clinically definite multiple sclerosis (CDMS), defined by the appearance of new neurologic or ophthalmologic events or progressive neurologic deterioration (>1.5 in EDSS score) with sxs persisting for at least 48 h Compared with placebo, IFN beta-1a IM reduced the 3-y probability of developing CDMS by 44% (P=.002) ETOMS (Early Treatment Of Multiple Sclerosis) Trial Primary end point: Time to dx of CDMS, defined by the appearance of new neurologic events (2 neurological events in the CNS separated in time and location) The time 30% converted to clinically definite MS was 569 d for IFN beta-1a SC vs 252 d for placebo (P=.034) Beck RW et al. Am J Ophthalmol. 2001;131:154-155. Comi G et al. Lancet. 2001;357:1576-1582. Galetta SL. J Neuroophthalmol. 2001;21:292-295.

ETOMS: Delayed Progression to CDMS Proportion Without Confirmed CDMS IFN beta-1a SC Placebo Median time to second relapse in 30% pts 569 d (IFN beta-1a) vs 252 d (placebo) HR=0.65 (95% CI: 0.45 0.94) P=.034 Time Since Randomization (d) LANCET by Comi G. Copyright 2001 by Elsevier Health Science Journals. Reproduced with permission of Elsevier Health Science Journals in the format electronic usage via Copyright Clearance Center. Comi G et al. Lancet. 2001;357:1576-1582. CHAMPS: Delayed Progression to CDMS Clinically Definite MS (%) 50 40 30 20 10 0 Rate ratio=0.56 (95% CI: 0.38 0.81) Log-rank P=.002 1 4 7 10 13 16 19 22 25 28 31 34 37 Months Placebo IFN beta-1a IM NEW ENGLAND JOURNAL OF MEDICINE by Jacobs LD et al. Copyright 2000 by Massachusetts Medical Society. Reproduced with permission of Massachusetts Medical Society in the format electronic usage via Copyright Clearance Center. Jacobs LD et al. N Engl J Med. 2000;343:898-904.

Recent CIS Studies BENEFIT (BEtaseron in Newly Emerging MS For Initial Treatment) Primary end point: Time to dx of MS using the McDonald Criteria; Time to dx of CDMS using the Poser criteria PreCISe (early glatiramer acetate treatment in delaying conversion to clinically definite multiple sclerosis [CDMS] in subjects presenting with a Clinically Isolated Syndrome) Primary end point: Risk of conversion to CDMS using Poser criteria Kappos L et al. Neurology. 2006;67:1242-1249. Comi G. Late-Breaking Session American Academy of Neurology, Platform Presentation. April 18, 2008;Chicago, Ill. BENEFIT Trial BEtaseron in Newly Emerging Multiple Sclerosis For Initial Treatment A 96-wk, double-blind, placebo-controlled, randomized, phase 3 study of IFN beta-1b, 250 mcg every other day SC, vs placebo in CIS patients. Prospectively planned analysis at 3 y post randomization and 2-y follow-up (5 years post randomization) February 2002 to ongoing 20 countries, 98 study sites 487 patients randomized 392 patients completed y 3 Kappos L, et al. Neurology. 2006;67:1242-1249.

IFN Beta-1b Reduces the Rate of Conversion to McDonald MS Placebo 85% McDonald MS (%) IFN beta-1b 69% P<.0001, 46% reduction for IFN beta-1b vs placebo (proportional hazards regression) NEUROLOGY by Kappos L et al. Copyright 2006 by Lippincott Williams & Wilkins, Inc. - Journals. Reproduced with permission of Lippincott Williams & Wilkins, Inc. - Journals in the format electronic usage via Copyright Clearance Center Kappos L et al. Neurology. 2006;67:1242-1249. Immediate IFN Beta-1b vs Placebo/IFN Beta-1b Delays the Emergence of MS 100 618/255 = 2.42-fold increase Patients Without CDMS (%) *At 25 th percentile 90 80 70 25th percentile 255 618 Immediate IFN beta-1b 60 363 days Placebo/ IFN beta-1b 50 0 0.5 1.0 1.5 2.0 Time (y) Kappos L et al. Neurology. 2006;67:1242-1249.

Immediate IFN Beta-1b Reduced the Risk of a Second Attack by 41% at 3 Y vs Placebo/IFN Beta-1b Patients Not Converted to CDMS (%) 100 90 80 70 60 40 0 0.5 1.0 1.5 2.0 Kappos L et al. Lancet. 2007;370:389-397.. Time (y) 41% cumulative relative risk reduction at 3 y based on Hazard Ratio=0.59 50 49% P=.0011 2.5 3.0 63% Immediate IFN beta-1b Placebo/ IFN beta-1b Immediate IFN Beta-1b vs Placebo/IFN Beta-1b Reduced the Risk of Sustained Disability (1.0 EDSS Change Confirmed Over 6 Months) 100 40% cumulative relative risk reduction based on Hazard Ratio=0.6 Patients Without EDSS Progression (%) 90 80 70 P=.0218 84% 76% Immediate IFN beta-1b Placebo/ IFN beta-1b 60 0 0.5 1.0 1.5 2.0 2.5 3.0 Time (y) Kappos L et al. Lancet. 2007;370:389-397..

PreCISe Study Study Aim: To evaluate the safety, efficacy, and tolerability of glatiramer acetate 20 mg in subjects presenting with CIS Study Design: 3-year, multi-country, multi-center (80 centers), randomized, placebo-controlled, double-blind study 481 subjects equally randomized into 2 parallel treatment groups (glatiramer acetate 20 mg/matching placebo once daily SC) Comi G. Presented at AAN 2008, April 16, 2008; Chicago Ill. LBS.003. PreCISe Primary End Point Glatiramer Acetate Reduces the Risk to CDMS Subjects with CDMS (%) Risk Reduction of 45% Hazard Ratio= 0.55 [95% CI] 0.40-0.77 P=.0005 + 386 days: + 115% Placebo Glatiramer Acetate D 336 D 722 GA 20 mg n= 243 197 179 166 124 78 22 Placebo n= 238 197 165 136 98 55 15 Comi G. Presented at AAN 2008, April 16, 2008; Chicago IL. LBS.003.

Glatiramer Acetate Reduces the Proportion of Patients Who Convert to CDMS Odds Ratio 0.41 * *P<.0001 Comi G. Presented at AAN 2008, April 16, 2008 Chicago IL. LBS.003. Conclusions All three completed studies of IFN as well as the glatiramer acetate study in the CIS population have shown a statistically significant benefit 3-year BENEFIT study demonstrated that IFN-beta 1b significantly delayed disability progression from CIS Safety/tolerability of IFNs in CIS patients is consistent with the profile previously observed. Typical side effects of treatment did not have a negative impact on adherence The clinical paradigm has shifted toward earlier diagnosis and treatment (CIS population), potentially leading to better long-term outcomes

Rechallenge Question: Diagnosis and Treatment of CIS (1) Which of the following is true about the McDonald diagnostic criteria for MS? A. The McDonald criteria do not include an objective demonstration of dissemination of lesions in both time and space B. The McDonald criteria include a category for laboratorysupported MS based on CSF oligoclonal bands or elevated IgG C. MRI criteria are incorporated in the McDonald diagnostic scheme D. The McDonald criteria does not include possible MS Rechallenge Question: Diagnosis and Treatment of CIS (2) Which of the following is NOT correct concerning pharmacologic treatment of MS? A. Clinical trials to date suggest clinical outcomes are similar with delayed versus immediate treatment of patients with CIS B. BENEFIT is the only study to date showing an effect of treatment on delaying disability progression in the CIS patient population C. In PreCISe, glatiramer acetate reduced risk of clinicallydefinite MS by 45% versus placebo in CIS patients D. The safety/tolerability of interferons (IFNs) in CIS patients is consistent with the profile previously observed in patients with relapsing forms of MS

Part 3 Impact of Medication Tolerability: Recent Study Results and New Insights Into Keeping Patients on Medication Amy Perrin Ross, APN, MSN, CNRN, MSCN Neuroscience Program Coordinator Loyola University Medical Center Maywood, Illinois Treatment Options for MS Nonproprietary drug name Brand name Dosing regimen IFN beta-1a Avonex 30 mcg IM once weekly IFN beta-1a Rebif 22 or 44 mcg SC 3 times weekly IFN beta-1b Betaseron 0.25 mg SC every other day Glatiramer acetate Copaxone 20 mg SC once daily Natalizumab Tysabri 300 mg IV every 4 weeks Mitoxantrone Novantrone 12 mg/m 2 IV every 3 months Indications Relapsing forms of MS; first clinical episode and MRI consistent w/ MS Relapsing forms of MS Relapsing forms of MS; first clinical episode and MRI consistent w/ MS Relapsing forms of MS Relapsing forms of MS* Secondary progressive, progressive relapsing, or worsening relapsing-remitting MS *Generally recommended for patients who have had inadequate response to, or are unable to tolerate other MS therapies.

Patient s Perception of How Treatment Choice Was Made Number % 2500 2000 40.0% 2181 Total Starts Percent of Total 45.0 40.0 35.0 1500 23.7% 30.0 25.0 1000 500 1295 16.0% 875 12.8% 700 7.4% 402 20.0 15.0 10.0 5.0 0 My doctor made the decision My doctor discussed this treatment and asked for my agreement My doctor discussed all therapies and recommended this treatment I requested this treatment as a result of my own research My doctor asked me to pick one 0.0 Data on file. Teva Pharmaceuticals; 2008. How Treatment Choice Was Made: Effect on Discontinuance Number of patients % 2500 2000 1500 1000 500 0 2181 8.3% 181 My doctor made the decision Total Starts 90-Day Stops 90-Day Discontinuance Rate 1295 6.9% My doctor discussed treatment and asked for my agreement 6.7% 875 700 89 59 50 402 30 My doctor discussed all therapies and recommended this treatment I requested this treatment as a result of my own research 7.1% 7.5% My doctor asked me to pick one 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 Data on file. Teva Pharmaceuticals; 2008.

Safety and Tolerability of DMDs in MS DMD classes have different safety and tolerability profiles IFN beta-1a/1b: flu-like symptoms, injection-site reactions, headache, elevated liver enzymes* Glatiramer acetate: injection-site reactions, dyspnea, immediate post-injection reaction* Natalizumab: PML Mitoxantrone: cardiotoxicity, secondary leukemia *Several comparative trials have been conducted between drugs from these classes. The REGARD trial showed that SC IFN beta-1a was less well tolerated than glatiramer acetate. In the BEYOND trial comparing IFN beta-1b 500 mcg, IFN beta-1b 250 mcg, and glatiramer acetate, the rank order of increasing tolerability and adherence was IFN beta-1b 500 mcg, glatiramer acetate 20 mg, and IFN beta-1b 250 mcg. Coyle P. Presented at: ECTRIMS, October 14, 2007; Prague, Czech Rep. Cited in Multiple Sclerosis. 2007;13(suppl 2):S270. Press release available at http://www.drugs.com/clinical_trials/beyond-study-results-do-not-support-regulatory-filing-betaferon-500-mcg-2470.html. Studies Comparing Tolerability of IFN Beta-1b and Beta-1a (SC) COMFORT: injection-site pain was lower with IFN beta-1b vs IFN beta-1a (1.5 vs 7.1;P=.0018) and more pts had injections without reactions (71% vs 47%; P<.0001) 1,2 BRIGHT: more pts using autoinjectors were pain-free immediately (17% vs 5%), as well as 30 min (40% vs 16%) and 60 min (55% vs 31%) following injection of IFN beta-1b vs IFN beta-1a SC 3 CRISP: more pts had pain-free injections with IFN beta-1b vs IFN beta-1a (47% vs 27%); the mean pain severity score was lower immediately (1.0 vs 3.1), as well as 10 min (0.4 vs 1.7), and 60 min (0.3 vs 1.5) following injection 4 1. Hunter SF, et al. 18th annual meeting of the Consortium of Multiple Sclerosis Centers; June 2-6, 2004; Toronto, Canada. 2. Baum K, et al. 20th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 6-19, 2004; Vienna, Austria. 3. Baum K et al. Multiple Sclerosis. 2007;13:1153-1160. 4. Harris C et al. Int J MS Care. 2005/2006;7:132-136.

Optimizing Tolerability and Adherence of IFN Treatment: We re Doing Better Now Slower dose titration and use of NSAIDs/analgesics Higher adherence in an IFN beta-1b trial (BENEFIT) using analgesics/slow titration vs pivotal trials that did not (93.6% vs 82.5%) 1,2 Patient support programs A nursing support program increased 1-y adherence to IFN beta-1b vs historical rates (~90% vs ~70%) 3 Autoinjectors 1. Kappos L et al. Neurology. 2001;57:1969-1975. 2. Kappos L et al. Neurology. 2006;67:1242-1249. 3. Piccone MA et al. 17th annual meeting of the Consortium of Multiple Sclerosis Centers; May28-June 1, 2003; San Diego, CA. Promoting Adherence: Importance of the Multidisciplinary Team Approach Physical Therapist Primary Care Physician Psychiatrist Occupational Therapist Orthopedist Nurse/APN Patient Vocational Counselor Neurologist Physiatrist Psychologist/ Neuropsychologist Social Worker Urologist Speech Pathologist Courtesy of Amy Perrin Ross, APN, MSN, CNRN, MSCN.

Fostering Adherence Establish a sense of realistic hope and trust Educate, educate, educate Insist that family member be present for teaching sessions Set realistic expectations Ask to see injection sites at patient visits Re-evaluate injection technique annually or if patient relates problems Maintain role of advocate Courtesy of Amy Perrin Ross, APN, MSN, CNRN, MSCN. Strategies to Address Barriers Medication specifics Set realistic expectations Discuss dosing and consistent administration Address side effects Patient/caregiver issues Identify information gaps, provide education Assess patient s financial status; support wherever possible with resources Courtesy of Amy Perrin Ross, APN, MSN, CNRN, MSCN.

Management of Local Injection Site Reactions Warm mixed medications to room or body temperature Warm or ice site for 30 60 s before injection Inject immediatly after a shower Aerosolized ethyl chloride Local anesthetics (EMLA, Oragel, Lidoderm ) Bayas A, Rieckmann P. Drug Saf. 2000;22:149-159. Walther EU, Hohlfeld R. Neurology. 1999;53:1622-1627. Munschauer FE 3rd, Kinkel RP. Clin Ther. 1997;19:883-893. Injection Mechanics Consider autoinjectors Modify needle length for body mass index Avoid medication on needle tip Fully penetrate the skin to avoid intradermal infiltration Assure complete, vertical needle penetration into skin surface Postcare: Topical steroids for erythemia (avoid topical steroids at sites of infection or apparent abscess or necrosis) Courtesy of Amy Perrin Ross, APN, MSN, CNRN, MSCN.

Who Can Help? Neurologist Nurse Company-sponsored support Pathways (1-800-788-1467) Shared Solutions (1-800-887-8100) Lifelines (1-877-447-3243) MS ActiveSource (1-800-456-2255) Conclusions IFNs are better tolerated now than in the past Nurse Support Programs Dose escalation NSAID use Head-to-head studies show different tolerability profiles for IFN beta-1b, glatiramer acetate, and IFN beta-1a, which may affect patient adherence Given the importance of DMD use early in the course of MS, addressing tolerability and improving adherence is vital to controlling the disease Interdisciplinary interventions and nursing support can help overcome barriers to and improve adherence

Rechallenge Question: Tolerability and Adherence Strategies Which of the following is true concerning tolerability/adherence of disease-modifying drugs in MS? A. Use of analgesics and dose titration schedules have been shown to improve adherence to IFN beta-1b B. Adherence is highest when patients choose their own treatment without physician guidance C. Warming the medication has no impact on injection site reactions D. Autoinjectors are not useful with MS therapies Thank You