Multiple Sclerosis MS and Myasthenia Gravis MG Adam Woolley PharmD BCPS Assistant Clinical Professor a woolley neu edu REQUIRED Reading MS Dipiro 9th edition Chapter 39 Multiple Sclerosis see instructions on Blackboard re access MG http emedicine medscape com article 1171206 overvi ew Exclude DDx and Workup tabs only For upcoming active learning session ALS ALS Practice parameter update posted on blackboard Miller RG et al Neurology 2009 Oct 13 73 1227 Recommended Neurology 2009 Oct 13 73 1218 Multiple Sclerosis MS Objectives 1 Evaluate the appropriateness of a therapeutic regimen for acute relapse treatment 2 Compare and contrast disease modifying agents in terms of efficacy safety ease of administration place in therapy and patient specific considerations 3 Develop an evidence based treatment plan for pharmacotherapy based on MS disease course and patient specific factors including dose route and frequency of administration 4 Synthesize pertinent counseling points for a therapeutic regimen containing an ABC R agent 5 Identify therapeutic goals and outcome measures for a patient started on MS therapy Review objectives in Dipiro chapter Multiple Sclerosis Inflammatory demyelinating disease of CNS Demyelinated lesions sclerosis Cause of MS is unknown Possibly combination of genetic susceptibility and a non genetic trigger environment Smoking Vitamin D inversly proportional low increased risk Infections Epidemiology Epidemiology Etiology Environmental genetic factors Risk is higher for Women 2 1 Whites w Scandanavian ancestry Blacks more likely to have progressive form 1st degree relative with MS Above 37th parallel Dx peak in 4th decade Risk can change depending on geography age Young children 15 take on the risk of the area they live in Pathophysiology Pathophysiology of MS http www msif org en about ms demyelination html Clinical Presentation Tertiary symptoms Financial Personal Social Vocational Emotional Secondary symptoms Recurrent UTIs Urinary calculi Decubiti Depression URIs Poor nutrition Primary Symptoms signs Visual complaints optic neuritis Gait problems Paresthesias Pain Spasticity Weakness Ataxia Speech difficulty Psychological cognitive change Lhermitte s sign Fatigue Bowel bladder dysfunction Sexual dysfunction Tremor Disease Courses Relapsing remitting MS RRMS Primary progressive MS PPMS Secondary progressive MS SPMS Progressive relapsing MS PRMS Indicator Favorable Prognosis Age at onset Gender Initial symptoms Optic neuritis or sensory sx 40 years Female Low Attack freq in early disease Course of disease Relapsing remitting Progressive Unfavorable Prognosis 40 years Male Motor or cerebellar sx High Olsson T The new era of multiple sclerosis therapy Journal of internal medicine 275 4 2014 382 386 Relapsing remitting MS Inflammatory attacks on myelin and the nerve fibers themselves During attacks activated immune cells cause localized areas of damage creating the symptoms Relapses followed by partial or complete recovery periods remissions No disease progression occurs 85 of people are initially diagnosed with relapsing remitting MS Progression to SPMS occurs in 80 of pts Prognosis Life expectancy shortened only slightly pretty normal life Survival rate related to disability don t die from MS may die from fall or bed ridden secondary cause Mortality results usually from secondary complications pulmonary renal The Big Picture Modify disease course Maintain at baseline as long as possible Treat exacerbations Manage symptoms Improve function and safety Diagnosis There is no single test for diagnosing MS Diagnosis of exclusion Medical History Subjective information Physical Exam Balance coordination Laboratory Testing MRI look at black holes and hypodense regions CSF exam look for biomarkers Assessment Scales Kurtzke EDSS Evaluates neurologic functions Limitations in measuring cognition fatigue affect Value range 0 no disability to 10 death 5 walking on your own 8 wheelchair Assists with diagnosis Brain MRI cerebrospinal CSF and visual evoked potential McDonald Criteria VEP On previous slide Relapse Aka exacerbation or attack Conventionally defined as the development of new or recurring symptoms lasting at least 24 hours and separated from a previous attack by at least one month Different for every one unique This is not just brief needs to be at least 24h Treatment of Acute Exacerbations Methylprednisolone Shortens duration Takes 2 3 days to take action onset May delay repeat attacks for up to 2 years after optic neuritis Dose 500 1000 mg IV daily Duration Adverse Events 3 to 10 days Improvement in 3 to 5 days Sleep disturbance metallic taste BG GI upset FDA Approved DTM Brand Avonex Rebif Plegridy Betaseron Extavia Copaxone Aubagio Dimethyl Fumarate Gilenya Lemtrada Tysabri Novantrone Generic Interferon beta 1a Interferon beta 1a PEGinteferon beta 1a Interferon beta 1b Interferon beta 1b Glatiramer acetate Teriflunomide Tecfidera Fingolimod Alemtuzumab Natalizumab Mitoxantrone Goals of Therapy Reduce inflammation and axonal damage Decrease relapse rate if don t have tx relapse every 6 mos up to 5 years with tx Reduce progression of disability the longer ambulatory the better Slow accumulation of lesions on magnetic resonance imaging MRI From Chapter 39 Multiple Sclerosis Pharmacotherapy A Pathophysiologic Approach 9e 2014 Date of download 1 21 2014 Copyright 2012 McGraw Hill Medical All rights reserved Legend Algorithm for management of clinically definite multiple sclerosis ABC R interferon 1a Avonex interferon 1b Betaseron Extavia glatiramer acetate Copaxone and interferon 1a Rebif IVIG intravenous immunoglobulin From Chapter 39 Multiple SclerosisPharmacotherapy A Pathophysiologic Approach 9e 2014 ABC R Avonex Betaseron Copaxone Rebif Interferon B 1b Brand names Betaseron Extavia Dose 250 mcg 8 million international units SC every other day Storage does not require refrigeration Betaseron Interferon B 1a Medication Dosing Avonex 30 mcg 6 million IU IM once weekly Available as 33 mcg 0 5 mL 4 per package Storage Refrigerate Room temperature 7 days Rebif 22 or 44 mcg SQ three times weekly Refrigerate Room temperature 30 days Plegridy 125 mcg SQ q 14 days Refrigerate Room temperature 30 days Protect from light Rebif autoinjector Interferon Warnings Liver dysfunction Severe leukopenia Thrombocytopenia Pregnancy Lactation none are considered safe Just treat with px steroids Severe depression These are associated with depression and MS pts are increased rate Don t