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Sep 4, 2021Liked by Gavin Giovannoni

I switched to Ocrevus from Tecfidera, in part due to persistent GI issues from the Tecfidera. My understanding is that Tecfidera drop-out due to GI issues is pretty common. I have read about some newer treatments similar in action to DMF that claim to be much easier on the stomach. Do you recommend Tecfidera over the alternatives for patients wanting that level of protection? If so, why?

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No, not necessarily; it is horses for courses and each DMT needs to be selected for each individual based on many factors. It is not simple choosing a DMT.

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I should have been more specific in my question. I was specifically wondering about other fumarate drugs such as diroximel fumarate (Vumerity) and monomethyl fumarate (Bafiertam), both of which claim to work like Tecfidera but with fewer GI issues. Ignoring cost or availability issues, wouldn't those be strictly preferred for people starting treatment with a fumarate, such as the subject of the case study?

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I think the fumarates all work in the same way and as long as there is enough PK & PD (pharmacokinetic and pharmacodynamic) data of equivalence why wouldn't you take the formulation with the least GI side effects?

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Hi Prof G,

What would you think about switching to Lemtrada instead as it’s more effective long term potentially? I’d personally be worried in my 30s switching to something less effective..

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Sep 4, 2021Liked by Gavin Giovannoni

Ps appreciate that wasn’t the question. But interested on your thoughts for someone this young?

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Yes. That is an option. This patient lives in the US, where the use of alemtuzumab is very low. The US label for alemtuzumab is quite restricted.

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Separate question: What would you think of moving this patient from a twice-yearly OCR treatment schedule to one-yearly? It seems her disease is well controlled by OCR. Perhaps reducing the frequency of OCR infusions could preserve therapeutic benefit while giving her annual windows for vaccine readiness? Also perhaps this strategy could lower the odds of long-term immunosuppression? Curious to hear your thoughts Prof G.

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Not sure this will derisk ocrelizumab, because the B cells may remain very low. In addition I think the current dose of ocrelizumab may even be too low to tackle what is going on in the CNS.

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Why don't you recommend an IRT, specifically cladribine, in this patient?

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That wasn't the question. However, cladribine is another option. I would recommend a similar washout period, i.e. about 9-12 months, before starting cladribine. In the UK this patient may not be eligible for cladribine because it is only licensed for highly active MS, whereas ocrelizumab is licensed for active MS.

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If she was eligible however how would you envision cladribine to work post ocrelizumab? Speculative, appreciated!

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