Helen C. Pervanas, Pharm.D. Associate Professor of Pharmacy Practice MCPHS Worcester/Manchester

Transcription

1 Helen C. Pervanas, Pharm.D. Associate Professor of Pharmacy Practice MCPHS Worcester/Manchester

2 Objectives Describe the pathophysiology, diagnosis and prognosis of MS Discuss disease modifying therapy (DMT) agents used for MS Compare medication costs and formulary considerations when choosing DMT agents Discuss factors that pertain to initiating, changing and discontinuing treatment for MS

3 Disclosures I have no actual or potential conflict in relation to this presentation.

4 Session Outline Prevalence and costs associated with MS Clinical course and diagnostic factors for MS Treatment considerations with DMT agents Initiate/stop/change treatment Costs/Insurance coverage/pas Pregnancy Patient cases

5 Living with MS Diagnosed in 2008 at age of 57 Uses a cane for ambulation Taking Ocrelizumab

6 Prevalence of MS in the U.S. Approximate estimates 400,000 persons in the U.S 1 Closer to 1 million based on MS Society 1.Niedziela N, Adamczyk-Sowa M, Pierzchala K. Epidemiology and clinical record of multiple sclerosis in selected countries: a systematic review. The International journal of neuroscience. 2014;124(5):

7 Costs associated with MS Estimated annual costs: $28 billion 2 Total lifetime cost ~ $4.1 million Newly diagnosed patients x more likely to be hospitalized 2 x more likely to have 1 or more ED visit 2.4 x more likely to have physical/speech and OT visits 2. Ma VY, Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arc.h Phys Med Rehabil. 2014;95(5): e Medicare. National MS Society website. Accessed 6/28/18

8 Pathophysiology Progressive condition Destruction of myelin Inflammation Oligodendrocyte death Plaque and lesion formation

9 Epidemiology/Risk Factor Ages Gender women>men Geographic: Utah, Kansas, Colorado, Virginia, California, North Carolina Arizona. The greater the distance from the equator the higher the prevalence. In US states above the 37 th parallel. Caucasians of Scandinavian decent Smoking Environmental Influences Stress

10 Diagnostic Criteria for MS Clinical presentation Lab Testing MRI Testing

11 Thompson AJ, Banwell BL, Barkhof F. Diagnosis of MS: 2017 revisions of the McDonald Criteria. The Lancet neurology 2018: 17;2:

12 MRI

13 Laboratory Findings Cerebrospinal fluid shows oligoclonal bands (IgG) Protein slightly elevated WBC slightly elevated

14 Clinical Course Relapsing remitting MS (RRMS) Clinically isolated syndrome first attack Relapse or exacerbation attack of symptoms Remission resolution of symptoms Secondary progressive MS (SPMS) Primary progressive MS (PPMS) Progressive relapsing MS (PRMS)

15 Indicators and prognosis Indicator Favorable Prognosis Unfavorable Prognosis Age of onset < 40 > 40 Gender Female Male Initial symptoms Optic neuritis or sensory s/s Motor or cerebellar symptoms; numerous symptoms Disability Late Early Attack frequency in early Low High disease Clinical course of MS RRMS Progressive Recovery after first event Good Poor T2 lesions Low load High load T1 black hole lesions Low rate High rate Lesion growth Slow Rapid Locations of lesions Single Multiple

16 Treatment approaches for patients with MS 1. Treatment of acute attacks 2. Symptomatic therapy 3. Disease modifying therapy

17 Disease Modifying Therapy (DMT) Reduce annual relapse rates Reduce likelihood of developing second attack Initiate therapy after diagnosis to reduce progression

18 Early treatment delays progression Clinically isolated syndrome (CIS) First clinical event Early treatment with DMTs can delay the conversion to clinically definite MS (CDMS) Rate of brain atrophy Disability

19 Treatment Considerations when initiating DMT Initiate treatment with a DMT: After diagnosis regardless of age After first clinical event and + MRI For those with progressive MS Respect patient preference

20 Assess medical health Comorbid conditions Depression Cardiac Concomitant medications Smoking

21 DMT agents for RRMS First line agents: Interferons Glatiramer Acetate Fingolimod Teriflunomide Dimethyl Fumarate

22 DMT agents for RRMS Second line: Alemtuzumab Natalizumab Mitoxantrone Ocrelizumab indicated for PPMS

23 Interferons Drug Dosing Route Monitoring Adverse effects Avonex Rebif Betaseron Extavia Plegridy 30 mcg once weekly 22 mcg 44 mcg 3 times weekly 0.25 mg every other day 125 mcg every 2 weeks IM SubQ SubQ SubQ Thyroid, LFTs, CBC, depression Thyroid, LFTs, CBC, depression Thyroid, LFTs, CBC, depression CBC, platelets, transaminase, new CVD, depression Hepatotoxicity, flu like s/s, HA, leucopenia Hepatotoxicity, flu like s/s, leucopenia Injection site rxns Hepatotoxicity, flu like s/s, leucopenia. Injection site rxns Flu like s/s, injection site rxns, HA

24 DMT Agents Drug Dose Route Monitoring Adverse effects Copaxone Glatopa 20 mg 40 mg 3 times weekly SubQ No monitoring Injection site rxns, neuromuscular weakness, flu like s/s Gilenya 0.5 mg daily Orally ECG, LFTs, CBC, BP, eye exams, renal function Aubagio 7 14 mg daily Orally CBC, K, Renal function, LFTs, screen for TB Tecfidera 240 mg twice daily Bradycardia, macular edema, back pain, infections, PML Acute renal failure, alopecia, hepatotoxicity, hyperkalemia, peripheral neuropathy Orally CBC, LFTs Flushing, pruritus, infection, lymphocytopenia

25 DMT Agents Monoclonal antibodies Drug Dose & Route Monitoring Adverse Effects Lemtrada 12 mg IV daily for 5 days followed by 12 mg IV for 3 days 12 months later CBC, renal, TSH, ECG, HPV, PML, skin exams HA, infusion rxns, fatigue, skin rash, infections, malignancy, autoimmune effects Ocrevus 300 mg IV on day one followed by 300 mg IV two weeks later then 600 mg IV every 6 months after first dose Hep B, infusion rxns during infusion, malignancies, PML Infusion site rxns, URI

26 DMT agents Drug Dose Route Monitoring Adverse Effects Tysabri 300 mg every 4 weeks Novantrone 12mg/m 2 q 3 months IV infusion IV infusion LFTs, bilirubin, MRI, depression CBC, serum uric acid, LFTs, cardiac PML, leukocytosis, HA Myocardial toxicity, HF, leukemia, alopecia, UTIs

27 Treatment considerations when continuing treatment Promote continued adherence Continue treatment indefinitely unless the following occur: Suboptimal treatment response Side effects that are intolerable Inadequate adherence Better treatment option available

28 Switching DMT therapy Lack of efficacy over a 1 year period Experience 1 relapses New MRI detected lesions Increased disability Adverse effects/complications/abnormal labs Always check medication adherence first

29 Factors associated with non adherence Lack of efficacy (patient perception) Route of administration Risks Unable to tolerate self injectables (side effects and injection site reactions) High costs Psychosocial (depression, forgetting to take medication)

30 Pregnancy and DMTs DMTs may pose risk to the fetus Stop DMT before conception Should not initiate DMT during pregnancy unless MS activity outweighs risk

31 Pregnancy and DMTs Drug Interferons C Glatiramer Acetate B Recommendation Stop a few weeks or up to conception Natalizumab C Fingolimod C Dimethyl Fumarate C Novantrone D Teriflunomide Category X Avoid Stop 2 months prior to conception Need to undergo an accelerated elimination with cholestyramine at least 2 months before conception. Alemtuzumab C Maintain contraception for at least 4 months after last dose Ocrelizumab Maintain contraception for 6 months after the last infusion

32 Cost of DMT medications Drug Name Avonex $78,530 Rebif $84,766 Betaseron $83,276/$73,504 / Extavia Plegridy $157,040 Copaxone /Glatopa Gilenya $85,136 Aubagio $79,438 Tecfidera $79,716 Tysabri $88,800 Lemtrada $158,000 Yearly Cost (Source: Red Book) $89,213 (20mg) $78, 125 (40mg) & Glatopa $78,991 Ocrevus $58,500 first year then $78,000

33 Changes in costs of MS drugs 4 Drug Approval date Annual cost on approval 2013 annual cost Cumulative % change Interferon (Betaseron) Interferon (Avonex) Interferon (Rebif) Interferon (Extavia) 7/1993 $ 11,523 $ 61, % 5/1996 $ 8,723 $ 62, % 3/2002 $ 15,262 $ 66, % 8/2009 $ 32,826 $ 51, % 4. Hartung DM et al. Neurology 2015; 26: 84 (21):

34 Changes in costs of MS drugs 4 Drug Approval date Annual cost on approval 2013 annual cost Cumulative % change Glatiramer (Copaxone) Natalizumab (Tysabri) Fingolimod (Gilenya) Teriflunomide (Aubagio) Dimethyl Fumarate (Tecfidera) 12/1996 $ 8,292 $ 58, % 11/2004 $ 25,850 $ 64, % 9/2010 $ 50,775 $ 63, % 9/2012 $ 47,651 $ 57, % 3/2013 $ 57,816 $ 63, % 4. Hartung DM et al. Neurology 2015; 26: 84 (21):

35 Insurance coverage for patients living with MS Type of insurance coverage 6% 8% 33% 54% Private insurance Medicare Medicaid Uninsured Source: National Disability Institute (NDI) & Multiple Sclerosis Association of American (MSAA) ;2012

36 Strategies for managing costs Tiered formularies Step therapy Prior authorizations Quantity limits Disease management programs Case management programs

37 Insurance coverage and formulary considerations Insurance (may vary based on formulary type) Anthem BC/BS United Healthcare Harvard Pilgrim NH Medicaid Preferred Non Preferred PA required Avonex, Betaseron, Plegridy, Tecfidera, Glatiramer Avonex, Betaseron, Tecfidera, Copaxone Copaxone, Glatiramer, Tefidera, Gilenya Avonex, Betaseron, Gilenya, Rebif, Glatiramer Extavia, Rebif, Gilenya, Tysabri, Lemtrada Tier 3: Gilenya, Plegridy, Aubagio Tier 4: Rebif Glatopa/Extavia NC Tier 4: Rebif, Plegridy, Aubagio, Betaseron Plegridy, Extavia, Aubagio, Lemtrada, Tecfidera Yes Yes Yes; Tysabri, Lemtrada only if failed 2 or more other drugs PA required for non preferred agents, QL

38 PA Criteria Language Drug Lemtrada Criteria (Anthem) Inadequate response, adverse rxn, or contraindication to 2 preferred therapies and HIV negative Rebif/Extavia Tried on preferred interferon agents or tecfidera or glatiramer and + MRI findings or dx of RRMS/SPMS

39 Patient Assistance Programs Patient Access Network Foundation In alliance with MS Association of America (MSAA) Qualified individuals may receive up to $ 8,000/year Reside in US Covered by Medicare Drug Manufacturers (MAP)

40 Role of the pharmacist Educate patients on the side effects and monitoring of MS medications Stress adherence to medications! Educate and assist with prior authorization process Provide information on medication assistance programs

41 Patient Case LK LK is a 52 year old man who is healthy and an avid runner FH: No history of immunological or neurologic disease SH: Patient is a sales representative, does not smoke or drink Insurance plan prefers the following agents: Avonex, Betaseron, Gilenya, Copaxone Medications: Tolterodine LA 4 mg PO daily for overactive bladder

42 Patient Case 2012: Began to have pain from knees to ankles. Developed urinary frequency : Gradual worsening of symptoms 2017: After completing a ½ marathon he felt muscle weakness which was unusual for him present: Having difficulty walking. Urinary frequency and urgency have worsened. Frequent nocturia and is feeling depressed because he can no longer run and is going to counseling.

43 Neurologic Exam Minimal spasticity in right leg Deep tendon reflexes 2+ (normal) Bilateral babinski signs Gait is normal and can walk 25 feet in 4.4 seconds but is complaining of fatigue and aching in legs after walking

44 MRI and CSF Recent brain MRI shows 5 lesions, 2 of which are located in the spine. CSF shows some oligoclonal bands.

45 DMT therapies Which one of the following medications would be appropriate for LK? A. Avonex B. Glatiramer Acetate C. Mitoxantrone D. Fingolimod E. Dimethyl fumarate

46 Patient Case SR SR is a 28 year old woman who was diagnosed with MS 2 years ago. Current therapy includes fingolimod 0.5 mg orally daily. She and her husband are wanting to start a family. What recommendations would you provide to her regarding her therapy and becoming pregnant?

47 Patient case SR A. Continue therapy as it is completely safe B. Stop fingolimod a few weeks prior to conception C. Switch from fingolimod to natalizumab D. Stop fingolimod at least 2 months prior to conception

48 MS Management Pearls Start DMT treatment after diagnosis Continue DMT treatment Monitor for adverse effects Promote adherence Be aware of insurance coverage and assist with PA process Utilize disease management/case management programs

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