Multiple Sclerosis

  1. What are the phenotypes for MS?

    1. Clinically Isolated Syndrome (CIS)

    2. Relapsing-Remitting MS (RRMS)

    3. Secondary Progressive MS (SPMS)

    4. Primary Progressive MS (PPMS)


  2. What are the names of the platform therapies used for MS treatments?

    1. Interferon beta-1b (Avonex, Betaseron, Extavia, Rebif), Peg Interferon beta-1b (Plegridy), and Glatiramer acetate (Copaxone, Glatopa)


  3. What are the names of the antineoplastics used for MS treatments?

    1. Mitoxantrone & Cladribine (Mavenclad)

  4. What are the names of the S1PR Modulators (imod) used for MS treatments?

    1. Ponesimod (Ponvory), Siponimod (Mayzent), Ozanimod (Zeposia), and Fingolimod (Gilenya)

  5. What are the names of the Fumarates used for MS treatments?

    1. Monomethyl fumarate (Bafiertam), Dimethyl fumarate (Tecfidera), and Diroximel fumarate (Vumerity)

  6. What are the names of the Pyrimidine Synthesis Inhibitors (ide) used for MS treatments?

    1. Teriflunomide (Aubagio)

  7. What are the names of the Monoclonal Antibodies (mAb) used for MS treatments?

    1. Natalizumab (Tysabri), Ocrelizumab (Ocrevus), Ofatumumab (Kesimpta), Rituximab Alemtuzumab (Lemtrada), and Ublituximab (Briumvi)

  8. Which of the following medications are used in the induction therapy?

    1. Alemtuzumab, Mitoxantrone, Cladribine, Rituximab, Ocrelizumab, & Natalizumab

  9. Which of the following medications are used in the escalation therapy?

    1. Fingolimod, Siponimod, Teriflunomide, Dimethyl fumarate, Diroximel fumarate, Interferon-beta products, Glatiramer acetate

  10. What are some Patient-Specific Concerns?

    1. Risk/benefit profiles of DMTs, Preferred route and frequency of agents, Cost/insurance benefits, Disease burden, Pregnancy planning, and Comorbidities

  11. GL is a 44-yo male with newly diagnosed Relapsed Remitting MS

    phenotype. He is concerned about the side-effects associated with

    disease modifying therapy and does not currently have active disease

    so would prefer to utilize an escalation strategy. Which medication

    would be most appropriate to initiate?

    A. Alemtuzumab

    B. Fingolimod

    C. Interferon-beta 1a

    D. Natalizumab

    1. C. Interferon-beta 1a

  12. What is the difference between escalation and induction therapies?

    1. escalation therapies starts by using safer medications with low side effects/efficacy while induction therapies start by using the more toxic drugs with high side effects/efficacy

  13. When should we use induction therapy?

    1. If a patient who just wants to start with a more toxic medication, prioritizing it’s high efficacy despite the side effects (ex: Alemtuzumab, Mitoxantrone, Cladribine Rituximab, Ocrelizumab, & Natalizumab)

  14. When should we use escalation therapy

    1. if a patient wants to start with a with a less toxic medication, prioritizing safety & low side effects, over efficacy ( ex: Fingolimod, Siponimod, Teriflunomide, Dimethyl fumarate, Diroximel fumarate, Interferon-beta products, & Glatiramer acetate)

  15. What are the common ADRs associated with interferons?

    1. Injection site redness + swelling

      • Flu-like symptoms: ~24 hrs after injection & usually resolve within 1-3 months

      • Menstrual irregularities

      • Exacerbation or new onset depression and/or suicidal ideation

  16. What are rare ADRs associated with Interferons?

    1. Transient shortness of breath

      • Tachycardia

      • Thyroid dysfunction

      • Decreased blood cell counts

      • Transaminitis

      • Injection site necrosis

      • Neutralizing antibodies (Nab)

  17. What do we need to monitor when a patient starts Interferons?

    1. CBC w/differential, LFT

  18. How often are do we monitor a patient on Interferons?

    1. every 6 months

  19. What are common symptoms to look out for while on interferons?

    1. Autoimmune disorders

      • Depression, SI, or other psychiatric disorders

      • New onset/worsening CVD

      • S/S thrombotic microangiopathy (HTN, thrombocytopenia, renal impairment)

  20. How what is the dosing unit associated with interferon agent?

    1. mcg

  21. What are the brand names for IFN-B1a?

    1. Avonex and Rebif

  22. How is IFN-B1a (Avonex) dosed?

    1. mcg IM once weekly

  23. Who can recieve IFN-B1a (Avonex)?

    1. patients with RRMS or CIS

  24. How is IFN-B1a (Rebif) dosed?

    1. mcg SQ 3 times a week

  25. Who can recieve IFN-B1a (Rebif)?

    1. patients with RRMS only

  26. What are the brand names for IFN-B1b?

    1. Betaseron & Extavia

  27. How is IFN-B1b dosed?

    1. mcg SC every other day

  28. Who can recieve IFN-B1b (Betaseron)?

    1. patients with CIS only

  29. Who can recieve IFN-B1b (Extavia)

    1. patients with RRMS only

  30. What is the brand name for Pegylated IFN-B1a?

    1. Plegridy

  31. How is Pegylated IFN-B1a (Plegridy) dosed?

    1. mcg IM/SQ every 14 days

  32. Who can recieve Pegylated IFN-B1a (plegridy)?

    1. patients with RRMS only

  33. What are the common ADRs associated with Glatiramer Acetate?

    1. Pruritis

      • Mild injection site pain

      • Post injection reaction (10%)

      • Chest pain

      • Flushing

      • Dyspnea

  34. What are the rare ADRs associated with Glatiramer Acetate?

    1. Edema

      • Tachycardia

      • Thrombocytopenia

      • Injection site atrophy/fibrosis

  35. What are the brand names for glatiramer acetate?

    1. Copaxone® & Glatopa®

  36. Who can recieve glatiramer acetate?

    1. patients with RRMS or CIS

  37. How is glatiramer acetate dosed?

    1. mg SC daily or 3 times weekly

  38. What is the appropriate dose unit for glatiramer acetate?

    1. mg

  39. How is glatiramer acetate monitored?

    1. using CBC w/differentials, LFTs, and latent infection screeming

  40. When comparing glatiramer acetate and interferon agents what is true about their Relapse reduction rates?

    1. their relapse reduction rate is equal

  41. When comparing glatiramer acetate and interferon agents what is true about their Exacerbation reduction rates?

    1. glatiramer acetate has higher

  42. When comparing glatiramer acetate and interferon agents what is true about their side effects?

    1. glatiramer acetate has less side effects than interferon agents which is why it is prefered

  43. (true/false) both glatiramer acetate and interferon agents are available as auto injectors where GA is dosed in mg and IFN is dosed in mcg.

    1. true

  44. GL has a history of major depressive disorder for which he takes citalopram 40mg PO daily and utilizes cognitive behavioral therapy on a routine basis. His past medical history is otherwise noncontributory. Which of the following first-generation medications would be most appropriate for GL?

    • Glatiramer acetate 20mcg IM daily

    • Glatiramer acetate 40mg SQ three times weekly

    • Interferon-beta 1a 30mcg IM weekly

    • Interferon-beta 1a 44mcg SQ three times weekly

    1. Glatiramer acetate 40mg SQ three times weekly

  45. what is the brand name for Natalizumab (ty-natalie)?

    1. Tysabri

  46. Who can use Natalizumab (Tysabri)?

    1. patients with CIS, RRMS, or SPMS

  47. What makes Natalizumab (Tysabri) so inconvenient?

    1. patients have to go to an IV infusion center every 4 weeks

  48. What is the Black Boxed warning for Natalizumab (Tysabri)?

    1. PML (Progressive multifocal leukoencephalopathy)

  49. What are the associated risk factors for PML in a patient on Natalizumab (Tysabri)?

    1. presence of anti-JCV Abs, duration of therapy, or immunosuppressant use

  50. Why is the REMS program required for patients on Natalizumab (Tysabri)?

    1. due to the risk of PML

  51. What should be monitored in a patient on Natalizumab (Tysabri)?

    1. Hepatic panel, JCV (q6months), MRI (q3-6 months, 12 months, then yearly), and latent infection screening

  52. If your patient is on Natalizumab (Tysabri) and experiences weakness, Vision changes, or Memory impairment, what are your next steps?

    1. Discontinue the offending agent

  53. What is the brand name for Alemtuzumab(all-mya’s-lemonade)?

    1. lemtrada

  54. Who is Alemtuzumab (Lemtrada) used for?

    1. patients with RRMS or SPMS

  55. When can patients use Alemtuzumab (lemtrada) (all-mya’s-lemonade)

    1. if patients have an inadequate response to 2+ previous agents

  56. What is the black boxed warning associated with Alemtuzumab (Lemtrada®)?

    1. possible autoimmune effect, infusion reactions, malignancy, stokes, or infection

  57. if a patient is taking Alemtuzumab (Lemtrada®), what do we need to monitor for toe prevent or reduce the risk of an autoimmune effect?

    1. Monitor CBC with differential, SCr, UA at baseline then monthly until 48 months after last dose

  58. if a patient is taking Alemtuzumab (Lemtrada®), what do we need to monitor and do for to prevent or reduce the risk of an infusion reaction?

    1. Consider premedication with corticosteroids, antihistamines, antipyretics. Monitor for 2 hours after each infusion. Make patients aware reactions can occur after 2 hours as well

  59. if a patient is taking Alemtuzumab (Lemtrada®), what do we need to monitor and do for to prevent or reduce the risk of Malignancy?

    1. Skin exams (baseline, yearly)

  60. if a patient is taking Alemtuzumab (Lemtrada®), what do we need to monitor and do for to prevent or reduce the risk of stroke?

    1. ECG at baseline

  61. if a patient is taking Alemtuzumab (Lemtrada®), what do we need to monitor and do for to prevent or reduce the risk of an infection?

    1. Administer PPX against PCP and herpes during treatment and 2+ months following last dose or until CD4+ counts > 200

  62. What are the common ADRs associated with Alemtuzumab (Lemtrada®)?

    1. Headache, Rash, Pyrexia, Nausea, Respiratory and urinary tract infections

  63. What is the brand name for Ocrelizumab?

    1. Ocrevus®

  64. Who can get Ocrelizumab (Ocrevus)?

    1. patients with CIS, RRMS, SPMS, or PPMS

  65. What are common ADRs for Ocrelizumab (Ocrevus)?

    1. infusion reactions, infections, malignancy or PML risks

  66. What are thing we can to to preven infusion reactions while on Ocrelizumab (Ocrevus)?

    1. Pre-medicate with 100mg IV meth-pred + antihistamine 30 minutes before infusion, consider APAP (tylenol), then monitor for at least 1 hour after infusion

  67. How is Ocrelizumab (Ocrevus) dosed for the first 2 infusions?

    1. Start and increase by 30ml/hr every 30 minutes to a max rate of 180ml

  68. How are later infusions for Ocrelizumab (Ocrevus) dosed?

    1. Subsequent 600mg infusions have a Max rate of 300ml/hr

  69. What are we monitoring for Ocrelizumab (Ocrevus)?

    1. Hepatitis B virus screening and Latent infection screening

  70. What is the brand name for Ofatumumab?

    1. Kesimpta

  71. who can get Ofatumumab (kesimpta)?

    1. CIS, RRMS, SPMS

  72. What are the common ADRs assosiated with Ofatumumab (kesimpta)?

    1. Injection site reaction, Infection, URTI, Headache, and PML

  73. What are we monitoring in a patient taking Ofatumumab (kesimpta)?

    1. Serum immunoglobulins, Hepatitis B markers, & Latent infection screen

  74. TZ is a 35-yo female recently admitted with Clinically Isolated

    Syndrome and a high risk of progression per the opinion of her

    neurologist. She has a fear of needles and will not be able to self administer any medications, but she would be willing to commute to

    an infusion center. She plans on an induction-based strategy for

    therapy initiation. Which of the following would be the most

    appropriate therapy?

    A. Alemtuzumab

    B. Glatiramer acetate

    C. Ocrelizumab

    D. Ofatumumab

    1. Ocrelizumab

  75. What are the brand names for Fingolimod?

    1. Gilenya® &Tascenso ODT®

  76. Who can take Fingolimod?

    1. patients with CIS, RRMS, or SPMS

  77. Fingolimod is contraindicated in people with which of the following?

    1. Patients with a QTc≥ 500msec, Concurrent use of Class Ia or III antiarrhythmic, Heart failure, MI, unstable angina, stroke, TIA, Mobitz type ii/iii AV block, or Sick sinus syndrome

  78. What are common ADRs in patient on fingolimod?

    1. Abdominal pain, nausea, diarrhea

      • Transaminitis

      • Headache

      • Cough, sinusitis

      • Bradycardia, atrioventricular block

      • Hypertension

      • Macular edema

      • Lymphocytopenia

  79. What should you monitor if your patient is taking fingolimod?

    1. 1st dose cardiac monitoring (BP/HR), consistent hepatic panel (2 months after stopping therapy, CBC baseline then q3months, latent infection screening, Varicella-zos virus Abs, S/sx PML, and an Opthalmologic exam: baseline, 3-4 months after treatment

  80. When do we want to monitor the ECG, HR, BP, S/sx of bradycardia?

    1. hourly for 6 hours after first dose

  81. When is continued observation required?

    1. •6-hour postdose HR < 45 bpm in adults; < 55 bpm if 12-18yo; < 60 bpm if 10-11 yo

      •6-hour postdose HR lowest postbaseline measurement

      •New onset second degree or higher AV block on repeat ECG

  82. What should you do if a patient dispays symptomatic bradycardia or prologned OTc?

    1. it requires an overnoght continuous ECG monitoring in the hospital

  83. Which anti-arrythmic agents should not be taken with fingolimod due to the risk of OTc prologation?

    1. amirodone/dronedarone, sotalol, Dofetilide, quinidine, procainamide, Disopyramide, and Ibutilide

  84. What are other risk factors for QTc Prologation?

    1. Hypokalemia, hypomagnesemia, antispychotics, antidepressants, and antinausea medications

  85. What is the brand for Siponimod?

    1. Mayzent®

  86. Who can get Siponimod?

    1. CIS, RRMS, or SPMS

  87. What is the Siponimod initial titration based off?

    1. CYP2C9 genotype

  88. Who is contraindicated in the use of Siponimod?

    1. patient with the CYP 2C9 3/3 genotype

  89. What is the brand name for Ponesimod?

    1. Ponvory®

  90. Who can take Ponesimod?

    1. patients with CIS, RRMS, or SPMS

  91. What are common adverse drug reactions for Ponesimod?

    1. Basal cell carcinoma (avoid in preexisting skin cancer) & Reduced FEV1 (COPD or Asthma)

  92. What is the brand name for Ozanimod?

    1. Zeposia

  93. Who can take Ozanimod?

    1. CIS, RRMS, or SPMS

  94. Who is Ozanimod contraindicated in?

    1. patients with concurrent use of MAO-I or Severe untreated sleep apnea

  95. What are common ADRs associated with Ozanimod?

    1. Decreased in forced vital capacity and FEV

  96. What is the brand name for Teriflunomide?

    1. Aubagio

  97. Who can use Teriflunomide?

    1. patients with CIS, RRMS or SPMS

  98. Who is contraindicated from using teriflunomide?

    1. patients with severe hepatic impairment or have a Coadministration with leflunomide

  99. What are common ADRs associated with Teriflunomide?

    1. Alopecia

      • Hypertension

      • Hypophosphatemia

      • Diarrhea, nausea

      • Lymphocytopenia, neutropenia

      • Headache

      • Transaminitis

  100. How should we monitor a patient on Teriflunomide?

    1. CBC, SCr, Hepatic panel monthly x first 6 months, Latent infection screening, Blood pressure, Electrolytes, & Pregnancy test at baseline (teratogenic)

  101. What are common drug-drug interactions associated with teriflunomide?

    1. Weak 2C8 inhibitors (avoid pioglitazone & repaglinide), Moderate 1A2 inducer (avoid Duloxetine & tizanidine), reduces INRby 25% with warfarin, and can increases the concentration oral contraception

  102. What is the Brand name for Cladribine?

    1. Mavenclad

  103. Who can take Cladribine?

    1. patients with RRMS or SPMS

  104. what is important about dosing for Cladribine?

    1. dosing is Weight-based over 2 years

  105. What is important about how Cladribine is administered?

    1. take Cladribine with water, with or without food and do not chew.

  106. How long should a patient wait to take their other medications before or after taking Cladribine?

    1. 3 hours

  107. Why does Cladribine need proper handling and disposal?

    1. it is cytotoxic

  108. What is the BBW for Cladribine?

    1. malignacy and teratogenic risk

  109. Who is contraindicated from using Cladribine?

    1. patients with malignancy, pregnant/breastfeeding patients, not using proper contraceptives, or has HIV

  110. What are the ADRs when using Cladribine?

    1. Decreased Hgb, thrombocytopenia, lymphocytopenia, Infection, Headache, & URTI

  111. What do we monitor for in patients taking Cladribine?

    1. CBC w/ lymphocyte count, Evaluate HIV, TB, HBV, HCV status prior to each course, VZV antibody status, Baseline pregnancy test, Hepatic panel prior to each course, MRI at baseline, & S/Sx PML

  112. Who can take Dimethyl fumarate, Monomethyl fumarate, and Diroximel fumarate?

    1. patients with CIS, RRMS, SPMS

  113. what are common ADRs for Fumaric Acid Derivatives?

    1. Flushing (take with food), GI disturbances, (abdominal pain, n/d, dyspepsia), Infection, & Transaminitis

  114. What are we monitoring in a patient on Fumaric Acid Derivatives?

    1. CBC w/ lymphocyte count (baseline, Q3 mon), Hepatic panel (prior initiation), Urinalysis (PRN), MRI (baseline), Latent infection screening, & S/Sx PML

  115. How should a patient take Diroximel fumarate?

    1. with food and limit fat to ≤30g and calories to ≤700

  116. SN is a 53-yo female with a past medical history of hypertension,

    atrial fibrillation, and type 2 diabetes. She is 70 kg. Her current

    medications include lisinopril 20mg daily, dofetilide 250 mcg BID, and

    metformin 1000mg BID. Her neurologist would like your opinion on

    which oral therapy would be most appropriate to start her on for her

    MS.

    • Cladribine 60mg PO daily x 4 days

    • Dimethyl fumarate 120mg PO BID

    • Fingolimod 0.5mg PO daily

    • Teriflunomide 7mg PO daily

    1. Dimethyl fumarate 120mg PO BID

  117. How are MS Exacerbations treated?

    1. Methylprednisolone 500-1,000mg/day IV 3-10 days

  118. What are common short-term ADRs associated with Methylprednisolone treatment?

    1. sleep disturbance, metallic taste (mouth), elevation of blood sugar (diabetics)

  119. What are common long-term ADRs associated with Methylprednisolone treatment?

    1. acne, fungal infections, mood alteration and GI hemorrhage (rare)

  120. In pregnancy, when is it okay to discontinue the medication?

    1. when the person has a relatively mild disease

  121. What are the first line options for a pregnant patient?

    1. Interferon or glatiramer acetate

  122. Why are Interferon and glatiramer acetate the drugs of choice?

    1. they have large molecules that prevents them from crossing the placenta and reaching the fetus and they have no fetal toxicity

  123. Which drugs are known teratogenics, and should not be used in pregnancy?

    1. teriflunomide, cladribine, natalizumab

  124. What are options if a pregnant patient needs a high efficacy agent?

    1. Natalizumab, Ocrelizumab, or Alemtuzumab

  125. How can a pregnant patient take Natalizumab?

    1. By extending interval to every 6-8 weeks, do NOT dose past 34 weeks, & consider switching to alemtuzumab or ocrelizumab

  126. How can a pregnant patient take Ocrelizumab?

    1. use bi-annual dosing, have a washout period for 4 months, and consider conception 1-3 months post infusion

  127. How can a pregnant patient take Alemtuzumab?

    1. Conception four months following treatment

  128. How can we treat Exacerbations in pregnant patient

    1. with methylprednisolone, Avoid in first trimester, & counsel that there is an Increased risk of LBW & cleft palate

  129. if a patient is breastfeeding which medication should they be on?

    1. interferons or glatiramer acetate

  130. Which medications are contraindicated while breatfeeding?

    1. fumarates, teriflunomide, ocrelizumab, S1PRs, cladribine, or alemtuzumab

  131. GA is a 34-yo female with RRMS that has recently been worsening in symptoms and disability. Her partner and her would like to grow their family within the next year before her disability worsens. She has been on natalizumab to this point and wants to ensure fetal safety while limiting her chances of relapse during pregnancy. Which of the following strategies would be most appropriate?

    • Continue natalizumab, but consider extending the frequency interval to every 6-8 weeks

    • Continue natalizumab at current dosing regimen as risk of discontinuing therapy abruptly

    outweighs benefits

    • Discontinue natalizumab and receive methylprednisolone doses as needed for

    symptoms peripartum

    • Discontinue natalizumab and initiate ocrelizumab with plans for conception 1-3

    months after dose

    1. Discontinue natalizumab and initiate ocrelizumab with plans for conception 1-3

      months after dose

  132. What is the first line treatment for pediactric treatment?

    1. Interferon Beta-1a or glatiramer acetate

  133. Which medication is only approved for DMT pediatrics?

    1. fingolimod

  134. Which vaccines are allowed to give a patient with MS?

    1. attenuated vaccines, covid vaccines, VZV antibody vaccine

  135. Which vaccines should not be given to a patient with MS?

    1. live vaccines

  136. What are spasticity treatment options for patients with MS?

    1. baclofen and tizanidine

  137. how are baclofen and tizanidine cleared?

    1. renally

  138. What are the ADRs for baclofen?

    1. CNS effects (dizziness, lethargy, confusion); withdrawal effects (rebound spasticity, hallucination, fever, HTN, seizure); n/v; hypotension; peripheral edema

  139. What are the ADRs for tizanidine?

    1. hepatotoxicity; hypotension; sedation; withdrawal (dysthermia, hallucinations, n/v)

  140. if a patient wants to improve their walking speed what drug should they use?

    1. Dalfampridine

  141. What are the ADEs for Dalfampridine?

    1. UTI, insomnia, constipation, nausea, headache, dizziness, dyspepsia

  142. What are pharmacotherapies that can help with sensory disturbances?

    1. Carbamazepine, Phenytoin, TCAs, Gabapentin, Pregabalin, Lamotrigine, & Topiramate

  143. Which medications can help patients with comorbid conditions of MS, Depression and anxiety?

    1. SSRIs or TCAs

  144. What are was to treat fatigue associated with heat, exertion, or even depression ?

    1. Amantadine, Modafinil, and Armodafinil

  145. TA is a 62-yo male struggling with MS symptoms, particularly spasms

    in his lower back making it difficult for him to keep up with his friends

    on the golf course. He is currently taking teriflunomide 7mg PO daily.

    Which therapy strategy may be most appropriate to alleviate these

    secondary symptoms?

    • Increase teriflunomide to 14mg PO daily

    • Start baclofen 10mg PO TID PRN

    • Start dalfampridine 10mg PO BID

    • Trial a back brace to improve posture

    1. Start dalfampridine 10mg PO BID