Q&A 99: treatment sequencing

An anti-CD20 therapy or cladribine? Or should I wait for tolebrutinib to become available?

Case

My last MS. DMT was in 2014 when I had the second course of Alemtuzumab, having previously been treated with Betaferon, Tysabri (Which I was taken off to have the supposedly good idea of a drug holiday and had a massive rebound. I was JC virus positive), and cyclophosphamide.

Alemtuzumab induced an early menopause and Graves' disease, including related eye issues.

Through various types of HRT, both systemic and topical, I'm on top of menopause related issues, including UTIs from which I no longer suffer. Graves' disease and the related eye problems are under control with carbimazole and various severe dry eye medications.

My MS has continued to deteriorate, so I have been offered treatment once again.

I had a recent exacerbation of symptoms, although I do not suffer from relapses as a rule.

Just as an aside, my hospital didn't offer a third course of Alemtuzumab because they chose instead to give more people two doses, which I believe was completely irresponsible because many of us now have these secondary autoimmunities without the potential benefit of the third dose!

Anyway.....,

Those on offer are ocrelizumab (Ocrevus), ofatumumab (Kesimpta) or cladribine (Mavenclad)

Currently, I'm concerned about infections, which I'm fortunately without at the moment, so I'm unsure about Ocrevus. However, are there fewer infections associated with Kesimpta? I did not think there would be fewer, but having spoken to people who take this drug, that is the general trend. Is this because it is a less potent drug?

As cladribine has always been discussed in relation to smouldering MS, hence the reason for the Chariot-MS trial, I am thinking this would be the best option as anti-CD20s are not promoted for smouldering MS.

What would be your advice?

My neurologist and hospital consider cladribine less effective and talk about the need for retreatment more times than is currently offered, hair loss and cancer.

Also, do you know what the criteria will be for the hopefully soon-to-be-released? BTK inhibitors? Will the medications you are on /or not on / or have been on play a role?

Having not been on any DMT for so long, would I be better off waiting for the BTKs or starting one of the three treatments being offered and hopefully transitioning to a BTK when available?

I have read your article, 'Game Changers,' which, as expected, praises cladribine and the BTK inhibitors, hopefully to be made available soon.

Obviously, with a significant element of smouldering involved in my MS, what would your advice be?

A middle-aged woman who is confused about deciding on what DMT to start. Image created by Gemini Pro 2.5

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Prof G’s answers

Your case is very complex and will therefore require a detailed discussion. I feel I need to start with the issues raised by your early menopause.

Q: Does alemtuzumab induce an early menopause?