Progress in MS: Current and Emerging Therapies Presented by: Dr. Kathryn Giles, MD MSc FRCPC The MS Society gratefully acknowledges the grant received from Biogen Idec Canada, which makes possible the Progress in MS: Current and Emerging Therapies session. The MS Society does not approve, endorse or recommend any specific product or therapy but provides information to assist individuals in making their own decisions.
Today’s Discussion • Treating MS • Management of the Disease • Questions & Answers Progress in MS | Page 2
Neuronal Damage Begins Prior to Clinical Presentation Clinically Relapsing Secondary Isolated Remitting Progressive Syndrome Clinical Symptoms First Clinical Attack Axonal Loss Clinical Threshold Demyelination Progress in MS | Page 3 Time (Years)
MS: Brain Volume and MRI Changes C. Relapsing Secondary Preclinical I. Remitting Progressive S. Brain volume Relapses and Impairment MRI Burden of Disease New lesions Time (Years) C.I.S., clinical isolated syndrome Progress in MS | Page 4 Adapted from Goodkin DE. UCSF MS Curriculum. January 1999
Disease Progression • Over 20-25 years, 80-85% of MS will progress from CIS to relapsing-remitting MS to secondary progressive MS • IT IS IMPORTANT TO TREAT EARLY Progress in MS | Page 5
TREATING MS Progress in MS | Page 6
MS Treatment Requires a 3-Pronged Approach 1. Management of acute attacks 2. Management of symptoms 3. Management of underlying disease Progress in MS | Page 7
Management Options for Acute Attacks Steroids • I.V. (methylprednisolone 1 g daily x 3-5 days) • High-dose oral (prednisone 1250 mg daily x 3-4 days) Either is acceptable 1 – Choice depends on regional facility and physician preference Steroids do not alter course of MS; only the duration and severity of that attack Progress in MS | Page 8 Morrow SH et al. Neurology 2004;63(6):1079-80.
Management of Symptoms • Depression • Spasticity • Bladder and bowel • Pain • Fatigue • Mobility • Sexual dysfunction Progress in MS | Page 9
Fampyra • New mobility drug • Can be used in both relapsing and progressive MS • Increases walking speed • Other effects – energy, cognition, stamina, arm function • 30% are super-responders, 30% some response, 30% no response • Determine effectiveness in 2 weeks • Common side effects (affect between 1 and 10 in every 100 patients): – Feeling unsteady, dizziness (risk of falling), headache, feeling, weak and tired, difficulty sleeping, anxiety, tremor (minor shaking), numbness or tingling of the skin, sore throat, shortness of breath, feeling sick (nausea), being sick (vomiting), constipation, upset stomach, back pain Progress in MS | Page 10
MANAGEMENT OF THE DISEASE Progress in MS | Page 11
Management of Disease • Goals of First Line MS Therapy (Avonex, Betaseron/Extavia, Copaxone, Rebif, Aubagio, Tecfidera) – Reduce the frequency, severity and duration of relapses – Preserve cognitive function – Slow or delay accumulation of disability due to disease progression – Prevent development of new lesions as seen on MRI scans – Keep people with MS functioning normally Progress in MS | Page 12
Injectable First Line Therapy • Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), Extavia (interferon beta-1b), Rebif (interferon beta-1a) – Comparable effectiveness (30% reduction in relapse frequency and severity; 80% reduction in MRI activity; modest slowing of disability progression) – Differences in side effects and injection frequency – Choose according to lifestyle, and patient choice – Safe and years of experience Progress in MS | Page 13
Tecfidera: New Oral First Line Therapy Tecfidera (BG-12; dimethyl fumarate) • Oral – Two pills, twice daily (120 mg) for a total of 480mg/day – One pill, taken twice daily (240 mg) for a total of 480mg/day • Side effects in first month of treatment include flushing, diarrhea, abdominal cramping, nausea • Minimal monitoring • Good early safety data • Likely as (or more?) effective than standard injectable drugs (49% relapse rate reduction; 90% reduction in MRI activity; slows disability progression over 2 years; reduction in brain atrophy; comparator arm with Copaxone in CONFIRM) Progress in MS | Page 14
Second New Oral: Aubagio (teriflunomide) – Daily oral agent, 14 mg pill once daily – Has recently obtained first line approval – Easy to use, easy to monitor and well-tolerated – Hair thinning, nausea, diarrhea – Possible effect on the developing fetus – women and men must use contraceptives – Need for washout if pregnancy or drug switch – Liver toxicity but otherwise good early safety – Effective (approximately equal to injectable DMT; 31% ARR reduction; 20% disability progression) Progress in MS | Page 15
Second Line Therapies Tysabri (natalizumab) • Monthly infusion • $$$$$, limited access • PML (new JC virus testing and now titre testing) – we can now manage risks • Effective (68% relapse rate reduction; 90% MRI activity reduction; slows disability progression) • Well-tolerated Progress in MS | Page 16
Second Line Therapies Gilenya (fingolimod) • Daily oral agent • $$$$, limited access • Significant need for monitoring – macular edema, cardiac, dermatalogic • Effective (54% ARR reduction; 30% progression; robust MRI effect) • Immunosuppressant • Limited safety data (varicella, zoster, macular edema, cardiac effects, PML, malignancies) Progress in MS | Page 17
Second Line Therapies Just Approved: Lemtrada (alemtuzumab) – IV – human monoclonal antibody – Very easy to give – first treatment course is administered by intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later – Highly effective c/w Rebif 44 (68% reduction in relapse rate; decreased MRI activity and brain atrophy; trend to decreased disability) – Seems to have sustained benefit at three years in extension trials – Immunosuppressant – don ’ t know how long effects last – no way to reverse – Long-term monitoring required – ITP, serious infection, thyroid, kidney Progress in MS | Page 18
Pipeline: 1-3 Years • Pegylated Interferon – Monthly or bi-monthly injections – Similar effectiveness to Avonex • Lingo – May help remyelination and reverse previous injury • Daclizumab – Another monoclonal antibody – Infrequent IV injections Progress in MS | Page 19
This Neurologist’s Approach to DMT: Old and New • Disease Factors — Severity of clinical disease (number and severity of attacks, EDSS score, cognitive function) — Appearance of MRI — Risk factors (age, gender) — Failure of first line DMT • Patient Factors — Age, gender, other health issues — Preference, lifestyle — Extended health plan, employment issues — Risk tolerance Progress in MS | Page 20
This Neurologist’s Approach to DMT: Old and New • Older DMT as First Line Therapy — Young — Female, wanting to have children — Mild disease, and relatively inactive MRI — No extended health benefits — Risk averse • New Orals as First Line Therapy — Older, Males — More severe disease – Tecfidera over Aubagio — Preference, lifestyle, injection phobia — Extended health plan, employment issues — Risk tolerance Progress in MS | Page 21
Realistic Treatment Expectations for All DMT, Both Old and New • DMTs may: — Delay progression to CDMS — Reduce the number and severity of acute attacks — Preserve ability to work, drive, and maintain and enjoy social relationships, leading to an improved quality of life — Slow down disease progression • DMTs will not: — Cure MS — Eliminate MS symptoms — Reverse existing damage to the CNS — Completely eliminate future disease Progress in MS | Page 22
Food For Thought: • Orals: — No more injections!!!! • But: — No DMT will cure MS or eliminate MS symptoms — We cannot compare agents one with another because of the design of clinical trials ( are new agents truly better?) — First line injectable therapies have over 20 years of safety data, and we understand the risks of adding in second line drugs when first line therapy fails — New agents have unknown risks Progress in MS | Page 23
THANK YOU Progress in MS | Page 24
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