Basic Neuroscience · Neuropharmacology
MS Disease-Modifying Therapies
Full referenceOpen or print the full PDFDownload PDFBy efficacy & MOAOpen or print the full PDFDownload PDF| Drug | Indication | Dose | Mechanism / effect | Side effects | Monitoring |
|---|---|---|---|---|---|
| Self-injectables | |||||
| IFN β-1a (Avonex, 1996) | RRMS | 30 mcg IM weekly | Modulates T- and B-cell function; downregulates inflammatory cytokines. ↓Relapses ~30%; ↓CIS→CDMS ~50% | Flu-like symptoms, headache, leukopenia, anemia, depression/suicide, hepatotoxicity, thyroid dysfunction, injection-site necrosis (SQ). Neutralizing antibodies. Pregnancy C | CBC, LFTs, TSH/free T4; screen for depression |
| IFN β-1a (Rebif, 1998) | RRMS | 44 mcg SQ 3×/wk | As above | As above; washout 1 month | As above |
| Peginterferon β-1a (Plegridy, 2014) | RRMS | 125 mcg SQ q2 wk | As above (pegylated) | As above | As above |
| IFN β-1b (Betaseron, 2009) | RRMS | 250 mcg SQ EOD | As above | As above | As above |
| Glatiramer acetate (Copaxone 1997, Glatopa 2015) | RRMS | 20 mg SQ daily or 40 mg SQ 3×/wk | Immunomodulator | Injection-site pain & lipoatrophy; post-injection reaction (chest/neck tightness, tachycardia, dyspnea, anxiety). No washout. Pregnancy B | None required |
| Ofatumumab (Kesimpta, 2020) | RRMS, active SPMS, CIS | 20 mg SC weeks 0/1/2, then monthly | Fully-human anti-CD20 mAb; B-cell depletion (self-injected) | Injection reactions, infections, ↓ immunoglobulins, HBV reactivation. No live vaccines | Pre: HBV screen, Ig levels, LFTs, vaccines; then infections/Ig/LFTs |
| Oral | |||||
| Fingolimod (Gilenya, 2010) | RRMS | 0.5 mg daily | S1P-receptor modulator; sequesters T-cells in lymph nodes. ↓Relapses 54%, ↓EDSS 30%, ↓MRI 74% (T2) | Bradyarrhythmia/AV block, macular edema, PRES, lymphopenia, PML, transaminitis, VZV meningoencephalitis, malignancy. Pregnancy C; washout 2 mo | Pre: CBC, EKG, LFT, VZV IgG (vaccinate if neg); 1st-dose monitoring; then CBC/LFT q6m, fundus at 6m |
| Siponimod (Mayzent, 2018) | RRMS, SPMS | 2 mg daily (titrate) | S1P modulator (subtypes 1 & 5, spares 3 → less cardiac). ↓Relapses 55%, ↓disability progression 21%, ↓MRI 79% (T2) | Bradyarrhythmia/AV block, macular edema (1.8%), lymphopenia, PML, transaminitis, malignancy. Pregnancy C | Pre: CYP2C9 testing (avoid in 3/3), CBC, EKG, LFT, VZV IgG; fundus screen; then CBC/LFT q6m |
| Ozanimod (Zeposia, 2020) | RRMS, CIS, active SPMS | 0.92 mg daily (7-day titration) | S1P modulator (subtypes 1 & 5) | Bradycardia (less; no 1st-dose obs if no cardiac hx), macular edema, ↑LFTs, HTN, ↓lymphocytes; MAOIs contraindicated; tyramine-rich foods (HTN) | Pre: CBC, LFT, EKG, VZV, ophtho if DM/uveitis; then CBC/LFT, BP, skin |
| Ponesimod (Ponvory, 2021) | RRMS, active SPMS, CIS | 20 mg daily (14-day titration) | Selective S1P₁ modulator | Bradycardia (titration), macular edema, ↑LFTs, HTN, ↓FEV₁, infections | Pre: CBC, LFT, EKG, VZV, ophtho; PFT if indicated; then CBC/LFT, BP, skin |
| Teriflunomide (Aubagio, 2012) | RRMS | 14 mg daily | Depletes pyrimidine pool; disrupts T-cell/APC interaction. ↓Relapses 31%, ↓EDSS 30%, ↓MRI 67% (T2) | Alopecia, hepatotoxicity. Pregnancy X (men & women); washout with cholestyramine/charcoal | Pre: LFTs, pregnancy test; then LFTs q6m, BP |
| Dimethyl fumarate (Tecfidera, 2013) | CIS, RRMS, SPMS | 120 mg BID ×7d then 240 mg BID | Activates Nrf2 antioxidant pathway; shifts Th1→Th2. ↓Relapses 53%, ↓EDSS 38%, ↓MRI 85% (T2) | Flushing 40% (give ASA), GI upset 15% (give with fatty food), transaminitis, lymphopenia, PML if lymph <500. Pregnancy C; washout 1 mo | Pre: CBC (lymph >1000), LFT; then CBC q6m |
| Diroximel fumarate (Vumerity, 2019) | CIS, RRMS, SPMS | 231 mg BID ×7d then 462 mg BID | Same active metabolite as DMF, less GI upset | Flushing 40%, less GI upset, transaminitis, lymphopenia, PML if lymph <500. Pregnancy C; washout 1 mo | Pre: CBC (lymph >1000), LFT; then CBC q6m |
| Monomethyl fumarate (Bafiertam, 2020) | CIS, RRMS, active SPMS | 95 mg BID ×7d then 190 mg BID | Bioequivalent active metabolite (MMF) of DMF / diroximel; Nrf2 activator | Flushing, GI upset (less), transaminitis, lymphopenia, PML if lymph <500. Pregnancy C; washout 1 mo | Pre: CBC (lymph >1000), LFT; then CBC q6m |
| Cladribine (Mavenclad, 2019) | RRMS (failed other drugs) | 4 cycles of 4 days at weeks 0, 23, 43, 66 (total 3.5 mg/kg) | Purine antimetabolite; depletes B & T lymphocytes. ↓Relapses 58%, ↓EDSS 33% | Headache, URI, lymphopenia (if <200 give acyclovir), liver injury, malignancy | Pre: CBC, LFT, HIV, TB, hepatitis panel, VZV IgG, cancer screen; then cancer screen, CBC |
| IV infusions | |||||
| Natalizumab (Tysabri, 2006) | RRMS | 300 mg IV q4 wk (max 3 yr; via MS TOUCH) | α4-integrin antagonist; blocks CNS lymphocyte migration. ↓Relapses 68%, ↓EDSS 42%, ↓MRI 83% (T2) | Infusion reactions, PML, neutralizing antibodies. Washout 3 mo | Pre: serum JCV Ab w/index; JCV Ab + PML screen q6m |
| Alemtuzumab (Lemtrada, 2014) | RRMS (failed 2 drugs) | 12 mg IV daily ×5d, then ×3d one year later (give steroids with first 3 infusions) | Anti-CD52; destroys T-cells, NK cells, monocytes. ↓Relapses 55%, ↓EDSS 30% | Infusion reactions; autoimmune (ITP 2%, thyroid 34%, anti-GBM 0.3%, hemolysis); cancer (thyroid, melanoma, lymphoma); HSV/VZV 16%. Pregnancy C; washout 3 mo | Acyclovir ppx; CBC, Cr, UA q1m ×48 mo; TSH q3m; yearly skin exam |
| Ocrelizumab (Ocrevus, 2017) | RRMS, PPMS | 300 mg IV ×2 (2 wk apart), then 600 mg IV q6 mo (pre-medicate steroids + antihistamine). SC option: Ocrevus Zunovo (2024) | Anti-CD20; depletes B-cells via ADCC & CDC | Infusion reactions (34%), breast cancer 0.7%, URTI. Contraindicated in active HBV; no live vaccines | Pre: HBV screen; observe 1 h post-infusion; delay if active infection |
| Ublituximab (Briumvi, 2022) | RRMS, active SPMS, CIS | 150 mg IV, then 450 mg at day 15 & q24 wk | Glycoengineered anti-CD20 mAb; B-cell depletion (ADCC) | Infusion reactions, infections, ↓ immunoglobulins, HBV reactivation. No live vaccines | Pre: HBV screen, Ig, LFTs; premedicate; observe post-infusion (first 2) |
How to choose a DMT
1 · According to type of MS
| MS type | Recommended DMTs |
|---|---|
| Relapsing MS (RRMS / active SPMS) | First line: interferons, glatiramer, fingolimod, siponimod, ozanimod, ponesimod, teriflunomide, dimethyl / diroximel / monomethyl fumarate, natalizumab, ocrelizumab, ofatumumab, ublituximab. Second line: alemtuzumab, cladribine |
| PPMS | Ocrelizumab |
2 · According to pregnancy category
| Pregnancy category | DMTs |
|---|---|
| Class B | Glatiramer acetate |
| Class C | Interferons, fingolimod, dimethyl fumarate, natalizumab, alemtuzumab |
| Class X | Teriflunomide |
| Not categorized | Ocrelizumab, ofatumumab, ublituximab, siponimod, ozanimod, ponesimod, diroximel & monomethyl fumarate, cladribine (newer agents — PLLR labeling). Cladribine contraindicated in pregnancy & active malignancy. |
3 · According to form of administration
| Route | DMTs |
|---|---|
| Oral | Fingolimod, siponimod, ozanimod, ponesimod, dimethyl / diroximel / monomethyl fumarate, teriflunomide, cladribine |
| IM | Interferon β-1a (Avonex) |
| SC | Interferons (Rebif, Betaseron, Plegridy), glatiramer acetate, ofatumumab |
| Infusion (IV) | Natalizumab, ocrelizumab, alemtuzumab, ublituximab |
4 · According to side-effect profile
| DMT | Limiting side effects |
|---|---|
| Interferons | Depression, hepatotoxicity, injection reaction |
| S1P modulators (fingolimod, siponimod, ozanimod, ponesimod) | Bradycardia, AV block, macular edema, lymphopenia, ↑ LFTs |
| Teriflunomide | Alopecia, hepatotoxicity, teratogenicity |
| Fumarates | GI upset, flushing (less with diroximel), lymphopenia |
| Natalizumab | PML risk |
| Alemtuzumab | Autoimmune disorders, cancer, HSV/VZV infection |
| Anti-CD20 (ocrelizumab, ofatumumab, ublituximab) | Infusion/injection reactions, ↓ immunoglobulins, HBV reactivation |
5 · According to screening measures needed
| DMT | Pre-screening | Follow-up labs |
|---|---|---|
| Interferons | CBC, LFTs, TSH | CBC, LFTs, TSH q6 months |
| Glatiramer | None | None |
| S1P modulators | ECG, CBC, VZV, LFT, ophtho (+ CYP2C9 for siponimod) | CBC, LFT, BP, skin exam, OCT q6 months |
| Teriflunomide | hCG, LFT, TB | ALT monthly ×6 mo then q6 mo, BP |
| Fumarates | CBC | CBC q6 months |
| Natalizumab | JCV Ab index, baseline MRI | JC titer q6 months |
| Alemtuzumab | CBC, Cr, TSH | CBC, Cr, UA q1m ×48 mo; TSH q3m |
| Anti-CD20 | CBC, hCG, HBV, Ig, vaccines | Ig & CBC periodically (CD19 optional) |
Neuro-Pharmacology — NeurologyResident.Net by Ahmed Koriesh