Consider
- risk/ benefit ratio
- patient features: age; disease duration; lesion burden; JCV; comorbidities; tolerance; pregnancy
- dosing: injectable; oral; infusion
- approach: eslation (safety) vs intensive (risks)
Efficacy
- modest (up to 34% red): glatiramer, interferon, teriflunomide
- moderate (up to 58% red): DMT, S1P modulator, cladribine
- high (up to 68% red): alemtuzumabm, natalizumab, anti-CD20
Modest
Glatiramer (Copaxone)
- MHC binding
- 6 months for effect
- SQ 40 mg 3x/wk or 20 mg/d
- no monitoring blood work
Interferon
INF- beta 1a (Avonex, Rebif); INF- beta 1b (Extavia, Betaseron); INF - beta 1a (Plegridy)
- inh cytokines
- flu-like symptoms and worse spasticity
- monitor: CBC w/ diff & LFT 1-3-6, then q3 mo; TSH q6 mo
Teriflunomide (Aubagio)
- inh DHO dehydrogenase
- 7 or 14 mg PO daily
- alopecia, diarrhea, and inc LFTs
- pretest: TB, pregnancy, LFTs
- monitor: CBC w/ diff and LFTs q6; if LFTs > 3x abnormal -> cholestyramine
Moderate
Fumarates
Dimethyl (Tecfidera); Diroximel (Vumerity)
- activates Nrf2
- 120 mg BID for 7d, and then 240 mg BID; 231 mg BID for 7d, and then 462 mg BID
- flushing (use ASA)
- pretest: CBC w/ diff
- monitor: CBC w/ diff & LFTs q3 mo for 1y; if ALC <0.8, switch
Mods
Fingolimod (Gilenya), Siponimod (Mayzent), Ozanimod (Zeposia), Ponesimod (Ponvory)
- S1P modulator
- once daily
- macular edema, bradycardia
- pretest: CBC w/ diff, LFTs, VZV, ophtho eval (4 mo after starting), derm eval (yearly, r/o skin cancer), pregnancy
- monitor: CBC w/ diff & LFTs 1-3-6, then q3 mo; if ALC <0.2, switch
Cladribine (Mavenclad)
- cytotoxic purine analog
- 1st year: 10 or 20 mg/d for 5d; after 30d, repeat; 2nd year repeat the same scheme
- URI
- pretest: CBC w/diff, HBV/HCV, HIV, LFTs, TB, VZV, pregnancy
- monitor: CBC w/ diff of 2&6 mo after cycle; if ALC <0.5, switch
High
Alemtuzumab (Lemtrada)
- CD52 ab
- 1st year: IV 12 mg/d for 5d (give steroids 3d); 2nd year repeat
- autoimmune thyroid disease
- pretest: CBC w/ diff, HBV&HCV, LFT, TB, TSH, VZV, UA, HPV screen, skin exam (annually)
- monitor: CBC w/ diff, Cr, and UA q1 mo; lymphocyte subset and TSH q3 mo
Natalizumab (Tysabri)
- VLA-4 antibody
- 300 mg IV q1-2 months
- PML, arthralgia
- pretest: CBC w/ diff, JCV, LFT, base MRI
- monitor: JCV & LFT q3 mo
*pregnancy up to 32 wks
PML surveilance
- JCV q3 mo
- if positive: bMRI looking for new lesions, serum natalizumab Ab, LP for JCV in CSF, hold infusion crossing to CD20 (do not hold > 4 weeks risk of rebound)
Negative: <0.2; Indeterminate: 0.2 - <0.4; Positive: >=0.4
Anti-CD20
chemiric (ximab), humanized (zumab), and fully human (umab)
rituximab (rituxan), ublituximab (briumvi), ocrelizumab (ocrevus), ofatumab (kesimpta)
- hypogammaglobulin and red vaccine efficecay
- pretest: CBC w/ diff, BMP, HBV&HCV, immunoglobulins (IgA, G, and M), lymphocyte subset (B&T), TB, VZV (shringrix vaccine, if negative)
- monitor: all tests before each infusion
* if IgG < 500 give IVIG
