Advancements In Treatment Options MS Relapses & Adherence


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Advancements In Treatment Options MS Relapses & Adherence. Presented by Scott Gold, MD April 27, 2013

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Advancements In Treatment Options MS Relapses & Adherence

  1. 1.  Present at seminars sponsored by the following pharmaceutical companies: Biogen-Idec EMD-Serono QuestCor Teva Neurosciences Engage in research for the following companies: Biogen-Idec Elan EMD-Serono Janssen Pfizer Roche Teva Neurosciences
  2. 2.  A disorder or group of disorders affecting the CNS -central nervous system (brain, spinal cord) An autoimmune process causing inflammation in theCNS in genetically susceptible individuals after one ormore triggers Inflammation involves myelin, causing demyelinationin the CNS, which leads to slower nerve conductionand reduced nerve signals controlling function Axonal injury and destruction occur early and areassociated with permanent neurological dysfunction
  3. 3. Joints: Rheumatoid Arthritis, Lupus, Psoriatic arthritisMuscles: Polymyositis; Neuromuscular junction: Myasthenia GravisPeripheral Nerves: Guillain Barré, CIDPSkin: Psoriasis, Dermatomyositis, LupusBlood Vessels: Lupus, Polyarteritis Nodosa, Temporal ArteritisBlood: TTP (platelet disorder)Sinuses: Allergic RhinitisThyroid: ThyroiditisLungs: AsthmaGastrointestinal: Crohn’s Disease, Autoimmune Hepatitis, UCKidney: GlomerulonephritisPancreas: Juvenile Diabetes
  4. 4.  Infection Lyme disease Neurosyphilis PML, HIV, HTLV-1 Inflammatory SLE Sjögren’s Other CNS vasculitis Sarcoidosis Behçet’s disease Guillain Barré Myasthenia Gravis NPH Trauma (chronic SDH) Vascular Multi-infarct state Metabolic Vitamin B12 and Edeficiencies Thyroid disorders CADASIL - rare/familial Cancer CNS lymphoma Paraneoplastic syndrome Congenital Chiari malformation Syringomyelia Degenerative Cervical spondylosis Motor neuron disease (ALSand SMA)
  5. 5. 1. Relapsing-remitting 2. Primary-progressive3. Secondary-progressive 4. Progressive-relapsingTime TimeTime TimeIncreasingdisabilityIncreasingdisabilityIncreasingdisabilityIncreasingdisabilityAdapted from: Lublin FD, Reingold SC. Neurology. 1996;46:907-911.5-10%66%ofRRMS5-10%80-85%
  6. 6.  Relapses Focal disturbances of function >24 hours Follows stability of at least 30 days In absence of environmental, metabolic, or infectiousprocesses Occur on average once a year in untreated patients (highlyvariable) Over time, frequency of relapses typically drops, even w/otreatment (so any treatment looks favorable if notcompared with placebo or other standard DMT’s)
  7. 7.  Prevent Relapses Treat Relapses Learn to recognize mimics / pseudoexacerbations Manage symptoms – acutely during relapses andchronically if they persist Delay progression to disability (DMT) Stabilizing or improving the MRI
  8. 8.  Non-Medical Management: Rest in a cool environment Symptomatic - treatment of individual symptoms: Cognition Fatigue Muscle spasms / stiffness Nerve pain / neuralgia Ataxia Bladder difficulties Seizures
  9. 9.  Medical Management: IV Therapy:- methylprednisolone, 500-2000 mg IV for 3-5 days, sometimesfollowed by a short course of prednisone over 1-3 weeks; MOA =cortisol effect on inflammation, stabilizing the BBB- Acthar gel, IM/SC, 80-120 units daily for 5-21 days (when IVsteroids are poorly tolerated or ineffective or if the patient haspoor IV access) – comparable in benefit and side effects, butdifferent MOA = cortisol + melanocortin effects (may haveadvantages over steroids, with loss cortisol effects and moreimmune cell effects in the brain and throughout the body) Oral steroids:- prednisone, methylprednisolone, or dexamethasone- high doses are more effective and reasonably well tolerated- used for people with poor IV access or can’t tolerate IV steroids Other Therapy: plasmaphoresis, IVIg, cyclophosphamide
  10. 10.  Diet: NMSS website. Also: The Zone Diet, by Dr. Barry Sears, hunter-gatherervariation by Dr. Terry Wahls: Vitamin D3 supplementation Exercise: stretching, weight training, aerobic conditioning; keep in the bestshape possible to be able to fight against any future challenges / attacks Sleep: quality and quantity Rest: planned rest periods for energy conservation Others: relaxation exercises, biofeedback, meditation, tai chi, yoga Foreign Substances: eliminate tobacco use alcohol (ok in small amounts - 1-2 beverages per day) marijuana (probably ok in small amounts) medications, especially sedatives, in combination with the aboveBe aware of conditions or factors that may mimic or aggravate MS symptoms stress, depression, sleep deprivation, medical conditions (UTI,bronchitis/lung disorders, thyroid disorders, heart disease), and effects ofmedications
  11. 11.  Educate yourself on all available treatments Adjust the intensity of treatment to the severity of disease (riskvs. benefit) Be realistic about what treatments can offer – they don’t cureMS and may only keep you from declining Treat early, stay positive, and stay committed to your chosentherapy. Don’t be afraid to change therapies if the current one isn’t rightfor you (intolerable side effects or not providing benefit); on theother hand, think twice about going off a therapy that isworking Be open and honest with your family, physician, and most ofall, yourself “MS is a marathon, not a sprint. It’s not how you start, but howyou finish that’s important.”- Dr. Randall Schapiro
  12. 12. Natural course of diseaseTheoretical ModelLater interventionLatertreatmentTreatmentat diagnosisIntervention at diagnosisTimeDisease onsetDisability
  13. 13. Currently not submittedFDA-approved therapies1995 2000 2005 2009 2010 2011AlemtuzumabExtavia®(IFNβ-1b)Gilenya™(fingolimod)Tysabri®(natalizumab)Betaseron®(IFNβ-1b)COPAXONE®(glatiramer acetate injection)Avonex®(IFNβ-1a)Rebif ®(IFNβ-1a)Novantrone®(mitoxantrone)LaquinimodApproval date2012 2013Aubagio(teriflunomide)DaclizumabTecfidera(DMF/BG12)
  14. 14. 18Lymph nodeBloodstreamNaïve T cellsAnti-inflammatory Th2 cells (MS-specific)• Multiple sclerosis is adebilitating autoimmunedisease characterized byboth inflammation andaxonal degeneration1• In order to regulate CNSdamage, treatment of MS isfocused on restoringimmune system balance2-5• It is important to expand ourview to consider treatmentimpact on the overallimmune response1. Kasper LH, et al. Neurology. 2010;74(Suppl1):S2-S8. 2. Ziemssen T. J Neurol. 2005;252(Suppl 5):V/38-V/45. 3. Yong VW, et al. Neurology. 2007;68(22 Suppl 3):S32-S37. 4. Dhib-Jalbut S. Neurology. 2007;68(22 Suppl 3):S13-S21. 5. Tzartos JS, et al. Am J Pathol. 2008;172(1):146-155.Proinflammatory Th1 cells (MS-specific)
  15. 15. 19MS-specific proinflammatoryimmune cells cross from thebloodstream into the centralnervous system (CNS),secrete proinflammatorycytokines, and eventuallydestroy myelin and facilitateneuronal death.1. Ziemssen T. J Neurol. 2005;252(Suppl 5):V/38-V/45. 2. Yong VW, et al. Neurology. 2007;68(22 Suppl 3):S32-S37. 3. Dhib-Jalbut S. Neurology.2007;68(22 Suppl 3):S13-S21. 4. Tzartos JS, et al. Am J Pathol. 2008;172(1):146-155.Proinflammatory cytokinesProinflammatory Th1 cells (MS-specific)Proinflammatory cellsrelease destructive cytokinesand neurotoxic agentsBlood-brain barrierTh1 cell crossingblood-brain barrier
  16. 16. Normal MSInflammatoryIFN-IL-12TNFInflammatoryIFN-IL-12TNFAnti-inflammatoryIL-4IL-10TGF-Anti-inflammatoryIL-4IL-10TGF-
  17. 17. Step 1: Main (Platform) medications Interferon beta (Avonex, Rebif, Betaseron, Extavia) Glatiramer acetate (Copaxone) Natalizumab (Tysabri) Fingolimod (Gilenya) Teriflunomide (Aubagio) Dimethyl Fumarate (Tecfidera)Step 2: Switch between the platform agents if an agent isineffective (based on several factors) or poorly toleratedStep 3: Add IV methylprednisolone or IM/SC ACTHAR (shortcourse vs. pulses); pulse therapy is not permitted incombination with TysabriStep 4: Switch to or add (except Tysabri) immunosuppressants Imuran, CellCept -> methotrexate -> cyclophosphamide or mitoxanthrone
  18. 18. Other alternatives: Experimental agents prior to release ontothe market; some protocols contain a placebo arm; relapsingand progressive MS (Melbourne, Vero Beach, Orlando,Maitland)Future oral agents (daily) - laquinimod (2013/2014)Infusions – alemtuzumab (IV yearly), rituxumab / ocrelizumab(IV every 6 months)Injections: daclizumab (IM every 2 weeks)Stem cells – currently limited to RRMSBone marrow transplantationImplanting stem cell and other immature cells, such asoligodendrocyte progenitor cells in brain / spinal fluid
  19. 19. Closely monitor disease activity and response to therapy Careful history of relapses, progression, and side effects of medications Neurological examination MSFC (Multiple Sclerosis Functional Composite: Timed 25ft Walk, 9-hole peg test, PASAT) EDSS (Expanded Disability Status Score): cognitive, visual, brainstem,motor, cerebellar, sensory, bowel/bladder Neuropsychological testing (Cognitive/Emotional) MRI’s of the brain and upper (C-/T-) spine Evoked potentials OCT / V.A. (especially with varying contrasts) / Visual Field testing Blood work (25-hydroxy-vitamin D levels, CBC/LFT’s) Quality of Life
  20. 20. The New Yorker
  21. 21.  The ability to follow the treatment planthat you and your health careprovider agreed upon (a contract) Average adherence = 50%
  22. 22.  Factors interfering with adherence: treatment (especially needle) fatigue loss of motivation / complacency financial challenges lack of curative benefit unrealistic expectations (of cure, reversal ofdisability, resolution of current symptoms) adverse effects of medications pregnancy doctor recommended against it treatment was “a hassle”
  23. 23.  Patients who stopped DMTs had: more severe disability, including SPMS more relapses poor to fair health depressed mood
  24. 24.  Reasons for never using DMT: my MS was not severe enough doctor didn’t recommend it or advised against it fear of DMT making things worse of causingadverse effects cost used other therapies fear of needles didn’t know about the DMTs
  25. 25.  Improving adherence: encouragement education, especially importance of treatment manage medication side effects injection technique and follow-up work with emotional issues (anxiety anddepression) recognize and work around cognitive deficits integrate a treatment schedule into the patient’slifestyle encourage a team approach – patient, family,friends, nurses, clinicians, self-help groups, andpharmaceutical support programs
  26. 26.  Determine what’s most important in your life - prioritizebased on your limitations at any given time Keep active with family and friends Be active in your church, synagogue, and community Improve your lifestyle - exercise regularly, do yoga and taichi, eat a balanced diet, with small amounts through theday, avoid tobacco, avoid excessive alcohol Look at the “big picture” – don’t sweat the small stuff Don’t dwell on the things you can’t change; focus on what’struly important…
  27. 27. Thank YouforYour Attention!
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