Table 2.
Characteristics of approved and commonly used disease modifying therapies for relapsing multiple sclerosis.
| Efficacy | DMT | * Reduction of ARR | Key Pharmacological Mechanisms | Important Adverse Effects | Risk of Malignancy on Long-Term Use |
Safety for Pregnancy |
|---|---|---|---|---|---|---|
| Low | IFNβ | 32–35% (compared to placebo) | Reduce antigen presentation and T cell proliferation, shift Th1 to Th2 response, restore suppressor function | Deranged LFT, flu-like Sx, skin reaction, depression | Nil | Safe (non-teratogenic) |
| Low | Glatiramer acetate | 29% (compared to placebo) | Alter T cell differentiation to induce proliferation of anti-inflammatory lymphocytes | Skin injection site reaction; lipoatrophy | Nil | Safe |
| Low | Teriflunomide | 34% (compared to placebo) | Inhibit proliferation of autoreactive B and T lymphocytes | Nausea, diarrhea, hair loss, deranged LFT, infection | Nil | Contraindi-cated in pregnancy, need accelerated elimination and organ screening USG if accidental pregnancy |
| Moderate | Dimethyl fumarate | 51% (compared to placebo) | Affect Nrf2 pathway activity, reduce release of inflammatory cytokines and activate antioxidant pathways (neuroprotective effects) | Flushing, gastrointestinal symptoms, lymphopenia, infection, low risk of PML (1 in 50,000); hypertension | Nil | Uncertain, inadequate data for conclusion |
| Moderate to high | S1P receptor modulators | |||||
| Fingolimod, | 54% (compared to placebo) | SIP receptor modulators: induce degradation of S1P receptors, trapping of lymphocytes in secondary lymphoid tissues | Headache, bradycardia, heart block, lymphopenia, infection especially herpes virus, PML (1 in 12,000), macular oedema, liver function derangement | Increased risk of malignancy (skin basal and Merkel cell carcinoma, melanoma) | Unsafe, increased risk of CA with exposure in first trimester, washout period of 2 months before pregnancy recommended | |
| Siponimod | 55% (compared to placebo) | similar to fingolimod | Headache, bradycardia, heart block, lymphopenia, hypertension, liver function derangement | Uncertain | Uncertain, risk of CA with exposure in first trimester unknown, likely similar to fingolimod, washout period of 10 days before pregnancy recommended |
|
| Ozanimod | 48% (compared to IFNβ1a) | similar to fingolomod | URTI, UTI, liver function derangement, bradycardia, heart block, lymphopenia, hypertension, orthostatic hypotension, back pain |
Uncertain | Uncertain | |
| Moderate to high | Cladribine | 58% (compared to placebo) | Nucleoside analogue, induce apoptosis of lymphocytes, followed by repopulation of lymphocytes | Lymphopenia, infection (no case of PML reported) | Possible increased risk of malignancy | Uncertain, conception at least 6 months after last dose recommended |
| High | Natalizumab | 69% (compared to placebo) | Bind to endothelial VCAM1 to prevent migration of lymphocytes to CNS | Infusion reaction, anti-drug antibody, infection, PML | Nil | Uncertain, SA and CA likely not elevated for exposure in first trimester |
| High | Alemtuzumab | 52% (compared to IFNβ1a) | Depletion of lymphocytes, monocytes, NK cells followed by repopulation of lymphocytes | Infusion reaction, infections especially herpes virus (not PML), secondary autoimmunity, stroke, arterial dissection, hemophagocytosis | Possible increased risk of malignancy including melanoma, thyroid cancer | Uncertain conception at least 4 months after last dose |
| High | Anti-CD 20 monoclonal antibodies | |||||
| Ocrelizumab | 46% (compared to IFNβ1a) | Depletion of CD20+ B cells | Infusion reaction, infection, lymphopenia, hypogammaglobulinaemia | Possible increased risk of malignancy | Uncertain, low teratogenic risk, conception 2 months after last dose | |
| Rituximab | 50% (compared to placebo) | Depletion of CD20+ B cells | Infusion reaction, infection, lymphopenia, hypogammaglobulinaemia | Nil | Uncertain, reduced B cell count in newborns, conception 1-3 months after last dose recommended | |
| Ofatumumab | 59% (compared to teriflunomide) |
Depletion of CD20+ B cells | Infection, lymphopenia, hypogammaglobulinaemia | Nil | Uncertain, conception 2 months after last dose recommended |
* Reduction of annualized relapse rate according to the published clinical trials which vary in the comparators including placebo and other comparator DMT such as interferon-beta and teriflunomide. CA = congenital anomalies; SA = spontaneous abortion.