Demographics of MS Age at onset15 to 45 years 1 Gender70% women 2 US incidence8,500 to 10,000 new cases per year 1 US prevalence350,000 2 1. Jacobsen DL et al. Clin Immunol Immunopathol. 1997;84:223-243. 2. Anderson DW et al. Ann Neurol. 1992;31:333-336.
Worldwide Prevalence of MS Worldwide distribution varies High prevalence 30+/100,000 –Northern United States and Canada –Most of Europe –Southern Australia –New Zealand –Northern Russia Kurtzke JF. Neuroepidemiology. 1991;10:1-8.
Pathology of MS An immune-mediated disease in genetically susceptible individuals Demyelination leads to slower nerve conduction Axonal injury and destruction are a ssociated with permanent neurological dysfunction Lesions occur in optic nerves, periventricular white matter, cerebral cortex, brain stem, cerebellum, and spinal cord Trapp BD et al. N Engl J Med. 1998;338:278-285.
Axonal Transection in Acute MS Lesions 64 m 45 m A B Reprinted with permission from Trapp BD et al. N Engl J Med. 1998;338:278-285. Copyright 1998 Massachusetts Medical Society. All rights reserved.
What Causes Demyelination and Axonal Loss in MS? Activation of autoreactive CD4+ T cells in peripheral immune system Migration of autoreactive Th1 cells into CNS In situ reactivation by myelin autoantigens Activation of macrophages, B cells Secretion of proinflammatory cytokines, antibodies Inflammation, demyelination, axonal transection, and degeneration
Immunopathogenesis of MS Th1+ Resting T cell MMP Activated (+) T cells Th1+ MMP BBBBloodCNS Th1+ TNF- IFN- B cell IL-2 Th1 APC
Immunopathogenesis of MS Th1+ MMP Activated (+) T cells Th1+ MMP Blood Resting T cell APC CNS TNF- IFN- B cell IL-2 Th1 APC BBB Th1+
Disability Progression and Disease Type Lublin FD, Reingold SC. Neurology. 1996;46:907-911. Relapsing-remitting Primary-progressive Disability Time Disability Secondary-progressive Progressive-relapsing Time Disability
Adapted from Weinshenker BG et al. Brain. 1989;112:133-146. Relapsing-remitting Primary-progressive Disease Type at DiagnosisDisease Type at 11-15 Years After Diagnosis (Among Those With RRMS at Diagnosis) Natural History Over Time Secondary-progressive Relapsing-remitting 42% 58% 15% 85%
Progression to Disability: EDSS Expanded Disability Status Scale (EDSS) Ordinal scale (range 0-10) measuring disability in increments of 0.5 Most widely accepted measure of disability in patients with MS Reflects impact of disease on neurological function Kurtzke JF. Neurology. 1983;33:1444-1452.
0 Normal neurological exam 1.0–1.5 No disability 2.0–2.5 Minimal disability 3.0–3.5 Mild to moderate disability 4.0–4.5 Moderate disability 5.0–5.5Increasing limitations in ability to walk 6.0–6.5 Walking assistance is needed 7.0–7.5 Confined to wheelchair 8.0–8.5Confined to bed/chair; self-care with assistance 9.0–9.5 Completely dependent 10.0 Death due to MS Progression to Disability: EDSS
Natural History Average is 1 relapse per year, fewer over time 1 25% of patients never lose ability to perform activities of daily living 1 15% become severely disabled within short time 1 Median time to reach EDSS of 6 is 15 years; to reach EDSS of 8 is 46 years 2 Mortality from MS as primary cause is low 1 1. Compston A, Coles A. Lancet. 2002;359:1221-1231. 2. Weinshenker BG et al. Brain. 1989;112:133-146.
Diagnosis of MS: Basic Principles Ultimately a clinical diagnosis; no definitive laboratory test Clinical profile Laboratory evaluation Evidence of dissemination of lesions in space and time Exclusion of other diagnoses Coyle P. In: Burks J, Johnson K, eds. Multiple Sclerosis, Diagnosis, Medical Management and Rehabilitation. New York: Demos; 2000:81-97.
Most Common Presenting Symptoms Sensory symptoms in arms/legs 1 33% Unilateral vision loss 1 16% Multiple symptoms at onset 1 14% Slowly progressive motor deficit 1 9% Diplopia (double vision) 1 7% Acute motor deficit 1 5% Others 1 16% Rarely seen 1 (eg, bladder dysfunction, heat intolerance, pain, movement disorders, dementia) 2 <5% 1. Paty DW. In: Burks J, Johnson K, eds. Multiple Sclerosis, Diagnosis, Medical Management and Rehabilitation. New York: Demos; 2000:75-76. 2. Paty DW, Ebers GC (eds.). Multiple Sclerosis. Philadelphia: FA Davis; 1998.
Diagnoses That Mimic MS Infection –Lyme disease –Neurosyphilis –PML, HIV, HTLV-1 Inflammatory –SLE –Sjögren’s –Other CNS vasculitis –Sarcoidosis –Behçet’s disease Cohen J, Rensel M. In: Burks J, Johnson K, eds. Multiple Sclerosis Diagnosis, Medical Management and Rehabilitation. New York: Demos; 2000:127-138. Metabolic –Vitamin B 12 and E deficiencies CADASIL, other rare familial diseases CNS lymphoma Cervical spondylosis Motor neuron disease Myasthenia gravis
Use of MRI in Diagnosis MRI is used to improve confidence in a clinical diagnosis of MS or to make a diagnosis of MS in clinically isolated syndromes 1 May show dissemination in space and time (eg, new lesions on follow-up MRI) 1 Total lesion load at diagnosis tends to be predictive of future disability 2 1. McDonald WI et al. Ann Neurol. 2001;50:121-127. 2. Brex PA et al. N Engl J Med. 2002;346:158-164.
MRI Basics in Diagnosing MS T1-weighted scan –Shows hypointense lesions (black holes) T2-weighted scan –Indicates total burden of disease –May show new lesions FLAIR image –Suppresses CSF –Useful for subcortical and cortical lesion identification Gadolinium enhancement –Highlights new or active lesions Costello K et al. American Journal for Nurse Practitioners. October 2000:9-26. Noseworthy JH. N Engl J Med. 2000;343:938-952.
MS Lesions on MRI T2 BOD T1/Gd postcontrast disease activity T1 precontrast black holes AB C T2-FLAIR D
McDonald WI et al. Ann Neurol. 2001;50:121-127. McDonald Diagnostic Criteria Preserve traditional diagnostic criteria of 2 attacks of disease separated in space and time –Must be no better explanation –Add specific MRI criteria, CSF findings, and analysis of evoked potentials as means of identifying the second “attack” Conclude that the outcome of the diagnostic workup should yield 1 of 3 outcomes: –MS –Possible MS –Not MS
McDonald MRI Criteria Abnormal MRI consistent with MS –Must have at least 3 of the following: 1 Gd-enhancing lesion or 9 hyperintense lesions if no Gd-enhancing lesion 1 or more infratentorial lesions 1 or more juxtacortical lesions 3 or more periventricular lesions –1 cord lesion = 1 brain lesion McDonald WI et al. Ann Neurol. 2001;50:121-127.
Reprinted with permission from Rudick RA et al. Neurology. 1999;53:1698-1704. Brain Atrophy
Secondary-progressive Relapsing-remitting Preclinical Disease Progression Time Adapted with permission from JS Wolinsky. Disability Measures of brain volume Relapses and impairment MRI burden of disease MRI activity
Goals of Disease Management Treating relapses Managing symptoms Modifying or reducing relapses and delaying progression to disability Facilitating an acceptable quality of life
Acute MS Relapses Relapses –Focal disturbances of function >24 hours –Occur about once a year in untreated patients –In absence of environmental, metabolic, or infectious processes Management: high-dose steroids –Common option: methylprednisolone IV for 5 days followed by short course of prednisone –Oral prednisone, oral methylprednisolone, or dexamethasone
Sources of Symptoms Symptoms vary widely in incidence and severity Sensory symptoms, Lhermitte’s Pain Proprioception Optic neuritis Diplopia Vertigo Dysarthria INO Tremor, Ataxia Cognitive loss Emotional disinhibition Bladder dysfunction
Symptom Management: Fatigue 75% to 95% of patients with MS have fatigue, which is often debilitating Rule out possible other causes, such as hypothyroidism, depression, anemia, heat exposure, sleep disorders, pulmonary dysfunction Shapiro RT, Schneider DM. Fatigue. In: Multiple Sclerosis in Clinical Practice; 1999. MS Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis; 1998.
Symptom Management: Fatigue Management includes: –Lifestyle changes –Effective energy expenditure –Pharmacologic interventions CNS stimulants, eg, amantadine and modafinil Antidepressants, eg, fluoxetine Shapiro RT, Schneider DM. Fatigue. In: Multiple Sclerosis in Clinical Practice; 1999. MS Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis; 1998.
Symptom Management: Pain Pain is a complex sensory phenomenon Multiple causes and types –Neuropathic –Musculoskeletal –Optic neuritis –Spasticity –Dystonia Costello K et al, eds. Nursing Practice in Multiple Sclerosis: A Core Curriculum. New York: Demos; 2003.
Costello K et al, eds. Nursing Practice in Multiple Sclerosis: A Core Curriculum. New York: Demos; 2003. Symptom Management: Bladder Dysfunction Failure to store urine, empty bladder, or both Symptoms include double voiding, hesitancy, frequency, urgency, incontinence, UTIs Evaluation: rule out UTI, check post-void residual (ie, amount of urine remaining after voiding bladder) Management –Antispasmodics –Tricyclic antidepressants –DDAVP (an antidiuretic hormone) –Alpha blockers –Intermittent self-catheterization –Indwelling catheter
Symptom Management: Bowel Dysfunction Caused by lesions in spinal cord Symptoms –Constipation is most common –Involuntary bowel –Diarrhea is uncommon Management –Constipation: fiber, fluids, activity, bowel training, laxatives, dietary modification –Involuntary bowel: fiber, anticholinergics, dietary modification Costello K et al, eds. Nursing Practice in Multiple Sclerosis: A Core Curriculum. New York: Demos; 2003.
1. Prosiegel M, Michael C. J Neurol Sci. 1993;115:S51-S54. 2. Rao SM. Curr Opin Neurol. 1995;8:216-220. Symptom Management: Cognitive Impairment Occurs in 45% to 60% of patients 1 but results in significant changes in only 15% 2 Manifests as short-term memory loss or impaired judgment, learning, word finding, or executive functioning Management –Neuropsychiatric testing –Compensatory techniques –Cognitive retraining –Disease-modifying therapies
Sexual Dysfunction/Intimacy Men and women can experience difficulties Libido Erection Frequency of orgasms Lubrication Bladder spasticity Depression Costello K et al, eds. Nursing Practice in Multiple Sclerosis: A Core Curriculum. New York: Demos; 2003.
Sexual Dysfunction/Intimacy Management strategies include –Pharmacologic management –Treat underlying symptoms –Adjust medications –Positioning –Lifestyle changes Key to successful management is open communication Costello K et al, eds. Nursing Practice in Multiple Sclerosis: A Core Curriculum. New York: Demos; 2003.
Disease Modification Aim to alter the natural course of the disease –Decrease relapses –Delay disability Two classes of disease-modifying medications: –Immunomodulators –Immunosuppressants Noseworthy JH et al. N Engl J Med. 2000;343:938-952.
MS Immunotherapy Nonspecific immunomodulation –Interferon beta-1b (Betaseron ® ), Interferon beta-1a (Avonex ®, Rebif ® ) Selective immunomodulation –Glatiramer acetate (Copaxone ® ) Nonspecific immunosuppression –Corticosteroids –Mitoxantrone (Novantrone ® ) –Cyclophosphamide (Cytoxan ® )* Experimental therapies* *These drugs do not have FDA approval for use in MS.
Type Recombinant proteinPolypeptide mixture Indication Reduce relapse frequency in RRMS SlowSlow accumulationaccumulationof disability How given 30 g IM 22 or 44 g SC 250 g SC 20 mg SC weeklyevery other day3x/weekdaily Relapse rate 18% 27%-33% 30% 32% (annualized)(2 years)(5 years)(long-term) Published data2 years4 years5 years8+ years IFN -1a (Rebif ® ) Nonselective and Selective Immunomodulatory Treatments IFN -1a (Avonex ® ) IFN -1b (Betaseron ® ) Glatiramer Acetate (Copaxone ® )
IFN -1a (Rebif ® ) Nonselective and Selective Immunomodulatory Treatments MRI findings ReducesReduces Reduces rateReduces lesions active lesions of new lesions lesions Reduces risk forReducesReduces rateReduces loss progressiondisabilityof severeof brain tissue of disabilityrelapses Common sideMild flulike symptoms,No flulike effects muscle aches, anemiasymptoms NoInjection-site reactions injection-site reactionsMenstrualSystemic disorders; mildpost- neutropenia andinjection thrombocytopenia;reaction abnormal liver function IFN -1a (Avonex ® ) IFN -1b (Betaseron ® ) Glatiramer Acetate (Copaxone ® )
Cytokine Imbalance in MS Normal MS Inflammatory IFN- IL-12 TNF Anti- inflammatory IL-4 IL-10 TGF- Th1 Th2 Th1 Th2
Potential Mechanisms of Action of IFN- in MS Antiproliferative effect Blocking T-cell activation Apoptosis of autoreactive T cells IFN- antagonism Cytokine shifts Antiviral effect Does not cross blood-brain barrier Indirect effects on CNS
Th1+ Resting T cell MMP Activated (+) T cells Th1+ MMP BBBBloodCNS Th1+ TNF-α IFN-γ IL-2 Th1 APC IFN- β Myelin protein Antigen Adapted from Yong VW. Neurology. 2002;59:802-808. Effects of IFN- at Blood-Brain Barrier
Glatiramer Acetate: Possible Mechanisms of Action Blocking autoimmune T cells Induction of anergy Induction of anti-inflammatory Th2 cells Bystander suppression Neuroprotection Neuhaus O et al. Neurology. 2001;56:702-708.
Th2+ Adapted from Yong VW. Neurology. 2002;59:802-808. Th2+ GA-induced T cell MMP Activated (+) T cells Th2+ MMP BBBBloodCNS IL-4 TGF-β B cell IL-10 Th2 APC Glatiramer acetate (GA) Myelin protein Bystander suppression Effects of Glatiramer Acetate at Blood-Brain Barrier
0.25 0.50 0.75 1.00 1.25 1.50 12345 Placebo Interferon -1b, 8 MIU Mean Number of Relapses 33%* Study Year 28% † 28% ‡ 30% ‡ 24% ‡ Adapted from IFNB Multiple Sclerosis Study Group. Neurology. 1995;45:1277-1285. *P < 0.001; † P < 0.05; ‡ P = NS. IFN -1b: Annual Relapse Rates Over 5 Years
Adapted from Jacobs LD et al. Ann Neurol. 1996;39:285-294. Mean Number of Relapses 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 All PatientsPatients Treated 2 Years Placebo Interferon -1a 18%* 32% † *P < 0.04; † P < 0.002. Interferon β-1a IM: Annual Relapse Rate
PRISMS Study Group. Neurology. 2001;56:1628-1636. Placebo/ Active 22 g 3 /wk 44 g 3 /wk PlaceboBoth IFN -1a Arms 0.72 0.80 1.02 1.5 52%47%32% P < 0.0001 0.0 0.5 1.0 1.5 2.0 Prior to Study Entry Mean Number of Relapses/Patient/Year At 4 Years Annual Mean Number of Relapses for IFN -1a SC
Placebo Glatiramer Acetate: Mean Relapse Rate Adapted from Johnson KP et al. Neurology. 1998;50:701-708. Glatiramer Acetate 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Mean Number of Relapses 24 Months24 Months + Extension 29%* 32% † *P < 0.007; † P < 0.002.
Glatiramer Acetate: 8-Year Data Annualized Relapse Rate P = 0.05 P = 0.01 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Relapse Rate (means) EntryPlacebo-Controlled Phase and Extension Placebo-Controlled Phase Through Open-Label Phase Glatiramer Acetate Placebo Placebo/Active Johnson KP et al. Neurology. 2002;58(suppl 3):A458. P06.079.
Mean Annual Relapse Rates of DMTs Nonrandomized, Open-Label Study Haas J et al. Presented at: AAN, 2003. INF β-1a IM INF β-1b SC GA INF β-1a 22 μg SC 1.4 1.2 1.0 0.8 0.4 0.6 0.2 0.0 Before Study 6 Months12 Months24 Months Mean Number of Relapses
ITT progression-free patients: all crossover vs 3 44 g: P = 0.07 Adapted with permission from PRISMS-4 Study Group. Neurology. 2001;56:1628-1636. Time (months) 061218 2430364248 1.0 0.8 0.6 0.4 Placebo/44 Placebo/22 3 443 22 Proportion of Patients IFN -1a SC: Proportion of Patients Free From Progression Over 4 Years
Time to progression: P = 0.096 Patients With Sustained Progression 1 EDSS Step Placebo46% (56/122) IFN -1b 8 MIU35% (43/122) Adapted with permission from the IFNB MS Study Group. Neurology. 1995;45:1277-1285. Probability (%) Days 018036054072090010801260144016201800 100 90 80 70 60 50 40 30 20 10 0 8 MIU Placebo 1.6 MIU IFN -1b: Probability of Avoiding Progression Over 5 Years
Johnson KP et al. Mult Scler. 2000;6:255-266. 01234567 Placebo/Active (n = 107) Glatiramer Acetate (n = 101) Time to worsening: P = 0.048 Open-Label Phase Placebo-Controlled Phase 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Survival Distribution Estimate Years Glatiramer Acetate: Time to Worsening by 1.5 EDSS Steps Over 6 Years (Open-Label Cohort)
Glatiramer Acetate: 8-Year Data Yearly EDSS Change From Baseline Change in EDSS Score Entry12*2* 3*3* 4*4* 5678 Year *P < 0.05. Glatiramer Acetate Placebo/Active P = 0.0279 (RMA) 0.8 0.4 0.7 0.6 0.5 0.2 0.3 0.0 0.1 –0.1 Johnson KP et al. Neurology. 2002;58(suppl 3):A458.
Glatiramer Acetate: 8-Year Data Categorical EDSS Change From Randomization to Last Observation 65.3 50.4 34.7 49.5 0 5 15 25 35 45 55 65 75 Improved/No ChangeWorsened Glatiramer Acetate Placebo/Active Patients (%) P = 0.0263 Johnson KP et al. Neurology. 2002;58(suppl 3):A458.
MRI Endpoints in RRMS Trials T2 Lesion Burden (Median % Change)* *Weekly doses reported. 1. Paty DW, Li DK. Neurology. 1993;43:662-667. 2. Comi G et al. Ann Neurol. 2001;49:290-297. 66 μg –15–10–505101520 P < 0.001 P = 0.36 P < 0.0001 IFN β-1b 1 IFN β-1a IM Placebo 175 μg 875 μg Placebo 132 μg 30 μg Placebo Glatiramer acetate 2 25 Placebo P = 0.001 140 mg IFN β-1a SC
IFN -1a IM: Change in Volume of Black Holes (Total Lesion Load) 0 25 50 75 100 125 150 PlaceboIFN β-1a IM Total Lesion Load (mm 3 ), Median Change From Baseline P = 0.065, NS n = 80 Simon JH et al. Neurology. 2000;55:185-192.
Active lesion—new or enlarging T2, new or persistently Gd-enhancing, avoiding double counting. The exact relation between MRI findings and the clinical status of patients is unknown. Panitch H et al. Neurology. 2002;59:1496-1506. 0 1 2 3 4 5 6 7 8 Week (4-Week MRI Scans) 04812162024 Mean Cumulative CU Active Lesions *P < 0.001 at Week 24 EVIDENCE Trial CU Lesions IFN β-1a 30 μg qw IM IFN β-1a 44 μg tiw SC
9.7 7.2 3.4 –6.2 –10 –5 0 5 10 Placebo/22 μg tiw SC (n = 57) Placebo/44 μg tiw SC (n = 49) IFN β-1a 22 μg tiw SC (n = 117) IFN β-1a 44 μg tiw SC (n = 111) IFN β-1a 44 tiw SC vs placebo/44 tiw SC IFN β-1a 22 tiw SC vs placebo/22 tiw SC IFN β-1a 44 tiw SC vs IFN β-1a 22 tiw SC Median Percent Change in Total T2 Lesion Area The exact relation between MRI findings and the clinical status of patients is unknown. PRISMS Study Group. Neurology. 2001;56:1628–1636 [correction in 57:1146]. P = 0.11 P = 0.003P = 0.009 IFN β- 1a SC Long-term Data: MRI T2 Lesions
Adapted with permission from the IFN β MS Study Group. Neurology. 1995;45:1277-1285. 6.7 21.0 30.2 11.9 18.7 3.6 –0.8 –3.8 –4.9 –5.6 12345 Placebo 8 MIU Median Change After Baseline P = 0.0363 Study Year P = 0.0012 P = 0.0015 P = 0.0002 P = 0.0055 35 –10 –5 0 5 10 15 20 25 30 IFN -1b: Median Change in MRI-Measured BOD 217 Patients Having at Least a Fourth-Year Annual Scan
Stone LA et al. Neurology. 1997;49:862-869. Months on Study (27 Subjects) 123456789101112 0 20 40 60 80 100 120 140 160 Total Enhancements 80%–90% response Interferon β-1b initiated Effect of IFN -1b on Enhancements
Adapted with permission from Comi G et al. Ann Neurol. 2001;49:290-297. This material is used by permission of John Wiley & Sons, Inc. Primary Endpoint: Cumulative Number of Enhancing Lesions (9 Months) 36.8 26.0 0 5 10 15 20 25 30 35 40 45 Lesion Number (mean + SE) –29% P = 0.0032 LOCF Placebo Glatiramer Acetate
Glatiramer acetate had significant effects on: ReductionP Value Total number of enhancing lesions (LOCF)29%0.003 Total number of enhancing lesions (as is)35%0.001 Total number of new enhancing lesions33%0.003 Total number of new T2 lesions30%0.003 T2 lesion volume (median, from baseline)40%0.001 Relapse rate (9 months)33%0.01 Comi G et al. Ann Neurol. 2001;49:290-297. European/Canadian MRI Trial: Summary
Glatiramer Acetate: Evolution to Black Holes 0 5 10 15 20 25 30 35 78 Lesion Age (months) Lesions Evolving Into Black Holes (%) P = 0.002 P = 0.04 31.4% 15.6% Filippi M et al. Neurology. 2001;57:731-733. Placebo Glatiramer Acetate 50%
Long-term Safety and Tolerability Issues: IFNs Flulike syndrome (fever, chills, fatigue) –Experienced by up to 75% of patients taking an IFN- β Injection-site reaction and necrosis Depression Liver function and bone marrow abnormalities Neutralizing antibodies PRISMS Study Group. Lancet. 1998;352:1498-1504. Freedman M. Presented at: The American Academy of Neurology 52nd Annual Meeting; April 29-May 6, 2000; San Diego, Calif. The IFNB MS Study Group. Neurology. 1995;45:1277-1285.
Neutralizing Antibodies Conflicting evidence regarding role of neutralizing antibodies in treatment failure 38% of patients in the IFN -1b trial developed neutralizing antibodies by the end of the third year 1 5% of patients in a recent weekly IFN -1a IM trial who had received drug for at least 1 year developed neutralizing antibodies 2 1. The IFN β Multiple Sclerosis Study Group. Neurology. 1993;43:655-661. 2. Avonex ® [package insert]. Cambridge, Mass: Biogen, Inc; 2003.
Glatiramer Acetate–Reactive Antibodies In clinical trials, patients treated with glatiramer acetate developed reactive antibodies that peaked at 3 months and decreased at 6 months 1 Development of these antibodies did not correlate with side effects and did not affect therapeutic activity of glatiramer acetate 1 Additional recent research confirms that reactive antibodies do not interfere with the biological functions of glatiramer acetate 2 1. Brenner T et al. J Neuroimmunol. 2001;115:152-160. 2. Teitelbaum D et al. Mult Scler. 2003;9(suppl 1):S37.
Long-term Safety and Tolerability Issues: Glatiramer Acetate Injection-site reaction Immediate postinjection reaction Copaxone ® [package insert]. Kansas City, Mo: Teva Marion Partners; 2000.
possibly no C B yes IFN yesno yesGA Menstrual disorders Pregnancy category Post- injection reaction Flulike symptoms Lab changes Injection- site reaction Safety and Tolerability Issues
Walther EU, Hohlfeld R. Neurology. 1999;53:1622-1627. Side Effect Management: IFN Flulike Symptoms Begin 3-6 hours after injection; last up to 24 hours Management: –Injection at night –NSAIDs or acetaminophen as comedications –Dose titration Not experienced with glatiramer acetate
1. Copaxone ® [package insert]. Kansas City, Mo: Teva Marion Partners; 2000. Side Effect Management: IFN Laboratory Test Abnormalities Obtain baseline complete blood count and differential and liver function values before initiation of therapy Monitor laboratory test values at regular intervals after initiation of therapy Consider dose adjustment or discontinuation of treatment if abnormalities persist Not indicated with glatiramer acetate 1
Side Effect Management: IFN Injection-Site Reactions Site rotation Ice to injection site Use of autoinjector Local wound care for skin necrosis
Side Effect Management: Glatiramer Acetate Injection-Site Reactions Site rotation Ice to injection site Use of autoinjector
Side Effect Management: Glatiramer Acetate Postinjection Reaction Occurs immediately after injection and consists of facial flushing, chest tightness, palpitations, anxiety, and shortness of breath Unrelated to serious sequelae Treatment steps: –Educate patient about possible occurrence –Reassure patient if reaction occurs –Instruct patient to sit upright in a comfortable chair –Refer for emergency care if no improvement in symptom intensity after 15-20 minutes
Facilitating an Acceptable QOL Quality of life (QOL) is the congruence between actual life conditions and one’s hopes and expectations MS, with its range of symptoms and its progressive nature, has a profound effect on QOL Maximizing QOL is an essential component of an optimal management strategy Includes comprehensive approach
Promoting Adherence Educate about the critical role of adherence in outcomes Recognize and address barriers to adherence Importance of clarifying realistic expectations Advocacy –Assistance with reimbursement –Identify resources –Involve family
Burden of disease Enhancing lesions Disease course Number of relapses Medical PatientConsiderations Lifestyle Expectations Capabilities Support system Factors That Influence Treatment Decisions