Kristen Helms, PharmD Clinical Associate Professor Department of Pharmacy Practice and Office of Teaching, Learning and Assessment Auburn University

Transcription

1 Kristen Helms, PharmD Clinical Associate Professor Department of Pharmacy Practice and Office of Teaching, Learning and Assessment Auburn University Harrison School of Pharmacy Auburn, Alabama

2 Presenter: Kristen Helms, PharmD Clinical Associate Professor Department of Pharmacy Practice and Office of Teaching, Learning and Assessment Auburn University Harrison School of Pharmacy Auburn, Alabama Moderator: Elena Beyzarov, PharmD Director of Medical Communications Saint Barnabas Medical Center Livingston, New Jersey Supported by educational grants from Teva Neuroscience, Inc. and Elan Pharmaceuticals, Inc.

3 Kristen Helms, PharmD, has no financial relationships with commercial interests to disclose related to this activity. Pharmacy Times Office of Continuing Professional Planning Staff Judy V. Lum, MPA, Jennifer Barrio, and Donna W. Fausak have no financial relationships with commercial interests to disclose related to this activity. The contents of this Webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

4 Evaluate current and emerging therapeutic strategies for slowing disease progression in patients with MS and their role in the treatment paradigm Describe common adverse events associated with MS therapies and strategies for mitigating these side effects Identify the role of pharmacy in maximizing outcomes and improving adherence in patients with MS

5 Pharmacy Times Office of Continuing Professional Education is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 1 contact hour (0.1 CEU) under the ACPE universal activity number H01- P. This activity is available for CE credit through December 15, If you received CE credit for the live version of this program held on December 15, 2011, you cannot receive additional CE credit for this enduring version. Type of Activity: Knowledge-based.

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7 Kristen Helms, PharmD Clinical Associate Professor Department of Pharmacy Practice and Office of Teaching, Learning and Assessment Auburn University Harrison School of Pharmacy Auburn, Alabama

8 There are 400,000 people with MS in the United States 10,000 new cases diagnosed annually Typical onset age years More common further from equator Vitamin D hypothesis Caucasian > other ethnic groups Women > Men Genetic link

9 Genetics Risk of patient with no family history: 1/250 Risk of patient with family history: 1/20 Risk of identical twin to patient with MS: 1/5 Location Environmental factors Viral Epstein-Barr (EBV) Bottom Line Etiology is not well-defined

10 Infiltration of inflammatory mediators to CNS through damaged blood vessels and damaged blood-brain barrier T-cells (Th1 and Th17) B-cells Demyelination of axons in the CNS Development of lesions in brain

11 Symptoms often non-specific Common sign/symptoms: Pain Depression Optic neuritis Paresthesias Weakness and ataxia Falls/gait changes Speech disturbances Bladder dysfunction/urinary retention Tremor Changes in cognition

12 10% Primary Progressive (PPMS) Clinically Isolated Syndrome (CIS) Relapsing- Remitting (RRMS) 85% 50% Secondary Progressive (SPMS) 5% Progressive Relapsing (PRMS) Clinically Definite MS (CDMS)

13 Taken from: Litzinger M and Litzinger M. Multiple Sclerosis; A therapeutic overview. US Pharm 2009:34(1):HS3- HS9.

14 Treatment falls into 3 main categories: Symptomatic therapies Corticosteroids (IV methylprednisolone) Management of acute attacks Supportive care Disease-Modifying Therapies (DMTs) Interferon beta-1a (Avonex, Rebif ) Interferon beta-1b (Betaseron, Extavia ) Glatiramer acetate (Copaxone ) Natalizumab (Tysabri ) Fingolimod (Gilenya ) Mitoxantrone (Novantrone )

15 Mechanism: Decrease IFN gamma release Decrease class II MHC gene expression Interferon β 1b (Betaseron, Extavia ) Interferon β 1a (Avonex, Rebif ) Dosing 250 mcg SC Q48 hr -Avonex 30 mcg IM weekly -Rebif 22 mcg/44 mcg SC TIW Available forms -Partially pre-mixed syringes -Formulation requiring no - refrigeration -Use with autojector -Prefilled syringe requiring refrigeration -Autojector (Rebif only) Annual Cost $20,000 -Avonex: $18,000 -Rebif: $19,000-21,000

16 Efficacy evidence compared with placebo: Reduction in attack rate of high-risk CIS patients Reduction in clinical relapse rate of RRMS (30%- 60% across trials) Reduction in total number of lesions (35%) No statistically significant changes in disability/quality of life found

17 Who is a candidate for therapy with interferon beta? Patients with CIS with high risk of developing active MS as first-line therapy Patient with RRMS or SPMS already experiencing relapses as first-line therapy

18 Common ADRs: Flu-like symptoms up to 24 hours after administration Usually resolve with continued therapy (up to 50% of patients) Injection site reactions (up to 20% of patients) More common/severe with Interferon β 1b Depression (up to 20% of patients) Rare and severe ADRs: Hepatotoxicity Thyroid dysfunction (hypo or hyper) Tachycardia Myelosuppression (panctyopenia, thrombocytopenia) Heart failure/cardiomyopathy Seizures in patients with h/o of seizure disorder Skin necrosis at injection site

19 Monitoring: CBC/platelets: at baseline, 1 month, then Q3 months X1year and q6 months, thereafter LFTs: at baseline, 1 month, then Q3 months X1year and q6 months, thereafter

20 Medication improves disease progression but NOT SYMPTOMS May significantly impact compliance Depression Common with disease and medication Should treat the depression, as it will unlikely resolve Signs and symptoms of severe ADRs Liver failure Heart failure Bone marrow suppression Storage of medication

21 Preventing or decreasing injection site reactions/flu-like symptoms: Rotate injection sites (must inject in thighs or buttocks) Use aseptic technique Warm medication to body temperature before administering Place ice on site of injection before and after administration Administer topical corticosteroids Take acetaminophen or NSAID before and at regular intervals for the next 24 hours Educate patient that these symptoms will lessen with use (after up to 3-6 months of therapy) Potential abortafacient Important given typically in women of child-bearing age

22 Mechanism: Binds class II MHC receptors preventing T-cell complex formation MBP-mimetic (myelin basic protein) T-cell suppression Dosing: 20 mg SC daily Available forms: Prefilled syringes requiring refrigeration Annual cost: $20,000

23 Efficacy evidence compared with placebo: Reduction in mean annual relapse rate of RRMS (up to 29%) Slowed progression of disability Candidates: Any patient with RRMS as first-line therapy

24 Common ADRs: Mild injection site reaction Single transient injections site reaction (16% of patients) Chest tightness/pain, SOB, flushing lasting up to 20 minutes NOTE: No depression or flu-like symptoms seen with glatiramer Rare ADRs: Antibody formation Lipoatrophy and skin necrosis at injection site

25 Use aseptic technique Rotate injection sites to one of following: Back of upper arm, within 2 inches of naval, area on side above hip, front of leg at least 2 inches above knee and 2 inches below groin Educate about one time injection site reaction Should be injected in office In patients with CAD, should closely monitor for chest pain Unknown effects in pregnancy

26 Mechanism: Monoclonal antibody (partial human) that targets α 4 β integrin on the surface of T-cells Blocks binding of VLA-1 to cell adhesion molecule Dosing: 300 mg IV Q4 weeks Annual cost: $31,000

27 Efficacy evidence compared with placebo: Reduction in clinical relapse rate of RRMS (up to 60%) Reduction in total number of lesions Decreases new gadolinium-enhancing lesions by up to 90% Improved quality of life measures Candidates: Patients with RRMS who have failed or had inadequate response to first-line therapies (ADRs) Should NOT be used in combination due to increase ADRs

28 Common ADRS: Headache and fatigue Rare ADRs: Anaphylaxis/urticaria (1%) Progressive multifocal leukoencephalopathy (PML) Removed from market in 2005 but reentered in 2006 Black Box Warning Patients must enter TOUCH program Appears to be duration-related

29 Patients must be educated on signs/symptoms of PML Therapy must be stopped immediately if these signs/symptoms arise Sudden vision changes, loss of strength, difficulty thinking Educate patient about TOUCH program: Prescriber and patient must be enrolled Pharmacies and infusion centers must be enrolled Requires specific education prior to initiation Requires screening prior to initiation and before each infusion Prescriptive follow-up plan with MD Patient must be provided with medication guide

30 Medication should not be administered if patient is immunosuppressed: Monitor for new prescriptions for HIV, cancer, chronic steroids (other than for acute MS symptoms)

31 Mechanism: Sphingosine-1 receptor agonist Decrease movement of T-cells into CNS Dosing: 0.5 mg PO Qday (higher doses associated with higher ADRs) Annual cost: $50,000

32 Efficacy evidence compared with placebo: Reduction in clinical relapse rate of RRMS Reduction in total number of lesions After 5 years of high dose (1.25 mg daily) therapy, >90% of patients had no gadolinium-enhancing lesions Improved quality of life measures

33 Common ADRs: Significant bradycardia with first dose Severe ADRs: Serious infections that resolve on discontinuation of drug Bradyarrythmias/AV block Macular edema Lymphoma Increase in LFTs Increase in blood pressure (1-2 mm/hg) Decrease in FEV

34 After first dose, obtain: BP and pulse Obtain at baseline: CBC EKG LFTs Ophthalmologic exam NOTE: due to the long t 1/2 (6-9 days), drug can remain in body up to 2 months after discontinuation

35 All patients should be provided with education on first dose bradycardia First dose must be administered in MD office with monitoring up to 6 hours Pharmacists should verify that this has occurred before dispensing first Rx or any Rx after patient has stopped for >2 weeks Educate on signs/symptoms of: Hepatic failure Macular edema Infection Time to full effect can be months due to t 1/2 so may not feel benefit immediately

36 Mechanism: Decreases lymphocyte proliferation Dosing: 12mg/m 2 IV over 5-15 minutes Q3 months Maximum lifetime; 140 mg/m 2 Annual cost: $8,000 depending on patient size

37 Efficacy evidence compared with placebo: Reduction in clinical relapse rate of RRMS, SPMS, and PRMS Improved quality of life measures

38 Common ADRs: Nausea/vomiting Alopecia Infections (URTI, UTI) Rare and Severe ADRs: Heart failure Leukemia (up to 1:145 patients)

39 Potential ADRs Signs/symptoms Heart failure (edema, SOB) Hair loss Signs/symptoms of infection Signs/symptoms of leukemia Be certain patients are being dosed appropriately based on body mass and are aware of maximum lifetime dose

40 Clinically Isolated Syndrome Studies suggests interferon beta at diagnosis decreases risk of progression to CDMS by 38% -46% CHAMPS: IM interferon beta-1a BENEFIT: Interferon beta-1b ETOMS: SC Interferon beta-1b (low dose) Glatiramer acetate decreased risk of progression to CDMS by 45% PreCISe Limited data suggests natalizumab or mitoxantrone may be used as induction therapy in aggressive disease

41 CIS or mild to moderate disease activity Interferon Glatiramer acetate Treatment Failure Natalizumab or fingolimod Natalizumab or fingolimod

42 Must consider efficacy: Natalizumab Mitoxantrone Fingolimod AND Must consider safety

43 Highly active disease Natalizumab Fingolimod Mitoxantrone

44 Teriflunomide Pyrimidine synthesis inhibitor Reduction in clinical relapse rate of RRMS (31%), decrease in total lesion volume, and decrease in disability Only safety concerns with rise in LFTs Fumarate and laquinimod Phase 3 trial results pending

45 Rituximab and ocrelizumab B-Cell inhibitors (anti-cd20) Significant decrease in lesions and relapse rates Ocrelizumab starting Phase 3 trials Alemtuzumab T-Cell and B-Cell inhibitor (anti-cd52) Significant reduction in relapse rates Significant ADRs may limit use: Immune thrombocytopenia purpura Phase 3 trials in progress

46 Daclizumab IL-2 antagonist/t-cell antagonist (anti-cd 25) In combination with Interferon beta, showed decreased lesions by MRI and potential decrease in annual relapse rate (not statistically significant) Safety profile promising

47 Most medications used for treatment of MS are: Specialty pharmaceuticals: biotech medication that structurally mimics compounds found in the body Inpatient/clinic administered Costly Associated with significant risks/adrs And the use of these drugs is growing with new efficacy data and early disease treatment

48 Work with third party insurers to help patients gain access to these medications Though most patients with MS are insured (90%), many medications are not covered, require prior authorization, or fall into specialty tier Medicare Part D Advocate for patient access with 3 rd party insurers Help with access to Medication Assistance Programs (MAPs) Assist with access to clinical trials

49 Coordinate drug distribution and delivery Ensure timely and accurate delivery of medication and ancillary supplies to homes Coordinate injection training support for patients and caregivers Educate patients about ADRs/risks and expected benefits Setting realistic goals REMS Prevention and management of expected or rare ADRs Reporting of ADRs through MedWatch and individual drug reporting systems Compliance monitoring Targeting reasons for non-compliance prospectively

50 Health maintenance education Vaccines Advice and support Provide information/advice through 24-hour support lines Patient support groups Assisting with access to disease management programs

51 Current DMT options for MS are few and often limited by ADRs or lack of perceived efficacy Pharmacists have a significant role Education on potential efficacy expectation Education on potential ADRs Education on reduction of ADRs Future therapies will likely offer many of the same therapeutic challenges, making the role of the pharmacist integral in patient compliance.

52 THANK YOU!