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Main attributes of licensed MS DMTs in relation to the COVID-19 pandemic (Version 7.0, 21-Dec-2020)
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At risk categoryRankClassTrade NameMode of actionEfficacyClassSafe to start treatmentAdvice regarding treatmentIn the event of COVID-19 infection?Immuosuppression?Need to shield?Response to future SARS-CoV-2 vaccineAttributes and caveats
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Very low1Interferon-betaBetaferon, Avonex, Rebif, PlegridyImmunomodulatoy (not immunosuppressive), pleitropic immune effectsModerateMaintenance immunomodulatoyYesContinueContinueNoNoLikely to be intact and live vaccine liklely to be safe.Has antiviral properties that may be beneficial in the case of COVID-19
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Very low2Glatiramer acetateCopaxoneImmunomodulatoy (not immunosuppressive), pleitropic immune effectsModerateMaintenance immunomodulatoyYesContinueContinueNoNoLikely to be intact and live vaccine liklely to be safe.-
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Very low3Cladribine / Alemtuzumab / Mitoxantrone / HSCTsee belowPost-immune reconstitution with normal innate and adaptive immunity (lymphocyte count > 1000/mm^3)High / Very highIRTN/AN/AN/ANoNoLikely to be intact' Live vaccine safe post immune reconstitution.Some patients who may have mitoxantrone or chemotherapy-induced (HSCT) cardiomyopathy may be at increased risk of severe COVID-19
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Very low4TeriflunomideAubagioDihydro-orotate dehydrogenase inhibitor (reduced de novo pyrimidine synthesis), anti-proliferativeModerate (1st-line) / Moderate to high (2nd-3rd-line)Maintenance immunomodulatoyYesContinueContinuePossible (no well-defined immunosupressive signature)NoLikely to be intact and live vaccine liklely to be safe.Has antiviral properties that may be beneficial in the case of COVID-19
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Low5Dimethyl fumarateTecfideraPleotropic, NRF2 activation, downregulation of NFΚβModerate (2nd-3rd-line) / High (1st-line)Maintenance immunosuppressiveProbablyContinue / Switch if lymphopaenicContinueYes, continuousNoLikely to be intact, unless lymphopaenic. Live vaccine contraindicated.The risk can only be considered low in paients who don't develop a persistent lymphopaenia. Patients with a total lymphocyte count of less than 800/mm3 should be considered be at a higher risk of develping complications from COVID19 infection.
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Low6Natalizumab (EID / extended interval dosing)TysabriAnti-VLA4, selective adhesion molecule inhibitorVery highMaintenance immunosuppressiveYesContinueContinue or miss infusion depending on timingYes, continuousNoLikely to be intact; live vaccine contraindicated.As COVID-19/SARS-CoV-2 is neurotropic natalizumab will potentially prevent viral clearance from the CNS; this risk is likely to be very low on EID or extended interval dosing. I stil have concerns about creating an environment in mucosal surfaces and the gut that may promote prolonged viral shedding; again this risk will be lower with EID.
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Intermediate7CladribineMavencladDeoxyadenosine (purine) analogue, adenosine deaminase inhibitor, selective T and B cell depletionHigh / Very high (highly-active RMS)IRT (semi-selective)ProbablyRisk assessment - continue or suspend dosingTemporary suspension of dosing depending on timingYes, intermittentNo, but need to be extra-vigilant until 3-month TLC > 500/mm3Possibly blunted if lymphopaenic. Unlikely if full immune reconstitutionOnly reduces the T-cell compartment by ~50% and has less of an impact on the CD8+ population. Provided total lymphocyte counts are above 500/mm^3 allowing appropriate antiviral responses should be maintained. Theoretical risk that in the immune depletion phase cladribine may result in prolonged viral shedding.
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Intermediate8S1P modulatorsFingolimod (Gilenya), Siponimod (Mazent), Ozanimod, PonesimodSelective S1P modulator, prevents egress of lymphocytes from lymph nodesHighMaintenance immunosuppressiveProbablyContinueContinue or temporary suspension of dosingYes, continuousNoBlunted response, but may be adequate. May need to switch DMT prior to a vaccination if concerned.Theoretical risk that S1P modulators may result in prolonged viral shedding. Paradoxically S1P modulators may reduce the severity of COVID-19; fingolimod is currently being trialed.
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Intermediate9Natalizumab (SID / standard interval dosing)TysabriAnti-VLA4, selective adhesion molecule inhibitorVery highMaintenance immunosuppressiveYesContinue, but consider EIDContinue or miss infusion depending on timingYes, continuousNoLikely to be intact; live vaccine contraindicated.As COVID-19/SARS-CoV-2 is neurotropic natalizumab will prevent viral clearance from the CNS.Intermediate risk; higher theoretical risk on SID. I have that natalizumab will create an environment in mucosal surfaces and the gut that may promote prolonged viral shedding.
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Intermediate/high10Anti-CD20Ocrelizumab (Ocrevus), Ofatumumab. Rituximab, UblituximabAnti-CD20, B-cell depleterVery highMaintenance immunosuppressiveProbablyRisk assessment - continue or suspend dosingTemporary suspension of dosing depending on timingYes, continuousNo, but extravigilance is requiredBlunted antidody responses, particularly to glycoprotein components of a vaccine. However, cellular immune response likely to be intact. Either to go ahead with vaccination or consider delaying vaccination until at least 12 weeks after last dose. No evidence that missing a dose and/or allowing B-cell reconstitution prior to vaccination will improve vaccine response.Does drop the both CD4+ and CD8+ T-cell populations by up to 20% and this may interact with other factors to affect antiviral responses. Theoretical risk that ocrelizumab and other anti-CD20 therapies may result in prolonged viral shedding. Swedish register data and an Iranian survey suggests that rituximab-treated patients are at higher risk of getting COVID-19 with a trend for higher rates of admission and ITU care. The latter results, although preliminary, are important and will need to be confirmed by other data sets and to see if the apply to ocrelizumab as well.
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High*11MitoxantroneNovatroneImmune depleter (topoisomerase inhibitor)Very highIRT (non-selective)NoSuspend dosingSuspend dosingYes, intermittentYesBluntedTheoretical risk that in the immune depletion phase mitoxantrone may result in prolonged viral shedding.
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High*12AlemtuzumabLemtradaAnti-CD52, non-selective immune depleterVery highIRT (non-selective)NoSuspend dosingSuspend dosingYes, intermittentYesBluntedTheoretical risk that in the immune depletion phase alemtuzumab may result in prolonged viral shedding.
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High*13HSCT-Immune depletion and haemopoietic stem cell reconstitutionVery highIRT (non-selective)NoSuspend dosingSuspend dosingYes, intermittentYesBluntedTheoretical risk that in the immune depletion phase HSCT may result in prolonged viral shedding.
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*risk refers to acquiring an infection during the immunodepletion phase. Post immune reconstitution the risk is low.
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Version 7.0 21-Dec-2020
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