The first is a patient with quite advanced MS who was reasonably well controlled on fingolimod. She moved to London to join her husband from a European country. She, unfortunately, ran out of fingolimod tablets before seeing me and by the time she arrived in our service she had rebound disease activity with severe brainstem and spinal cord disease activity. She was off her feet with the loss of bowel and bladder function.
The second case was also a European who has been living in the UK for 10 years. His first attack was a brainstem attack that occurred almost 2 years ago. He was initially seen in accident and emergency department of a district hospital. It took him almost a year to see a neurologist and then 6 months for a diagnostic workup to be completed before being referred to me. It took me just shy of 3 months to see him in my new patient MS clinic. By the time I saw him it was 21 months since he had his initial attack. His EDSS was 4.5. He now has bladder and bowel problems, unsteadiness of gait, double vision, weakness in his legs, incoordination in his limbs and depression. He has also lost his job and is unlikely to be able to resume work. His MRI is a full house of poor prognostic factors; high lesion load, Gd-enhancing lesions, posterior fossa and spinal cord lesions, black holes on T1 imaging and some early brain atrophy.
What did we do? We have put both these patients on natalizumab as part of our #BrainAttack paradigm, i.e. to get on top of the MS disease activity before we even have their JCV serostatus back. If they turn out to be JCV positive we can derisk their PML risk, by switching their treatment or offering them extended interval dosing (EID).
All MSologists have patients who have had catastrophic relapses whilst waiting for a diagnostic workup and/or DMTs. We also know that MS activity tends to be clustered, i.e. one of the best predictors of a relapse is a recent relapse. Instead of putting patients with possible early symptomatic MS at risk from having to wait why don’t we to treat them all with natalizumab to protect their brains and spinal cords? This is analogous to treating stroke.
Why natalizumab? It is one of our most effective DMTs, it works very quickly, it is given as an IV infusion, hence there is no problem with adherence and is very safe for up to 12 months. It is also relatively safe in pregnancy. During this 12 month period, the neurologist and the patient can then decide what strategy they want to pursue in the long-term. This could be to continue natalizumab long-term or to switch to another DMT, or in the case of an alternative diagnosis the drug can be stopped.
At Barts-MS we want to promote the #BrainAttack strategy and to potentially do a trial. Please note that if you adopt the #BrainAttack paradigm you need to commit to at least 6 months, and potentially 12 months, of natalizumab treatment, to prevent patients from developing anti-natalizumab or anti-drug antibodies. We rely on the continued administration of natalizumab to trigger high-zone tolerance and to switch off NAB development. We learnt about this when natalizumab was initially pulled from the market in the US after the initial PML scare. Those patients have 1, 2, 3 or 4 infusions were much more likely to become persistently NAB-positive and if this occurs they can never be treated with natalizumab again.
Please note that another issue with these two MSers is that they were both foreigners who grew up outside the UK and simply did not know how to navigate the NHS systems. I think everyone who lives in the UK knows how to navigate the NHS and to be more demanding. I am sure if these MSers had been native to the UK they would have found a way to expedite their appointments. This is no excuse. The tragedy for me is that both these MSers have acquired significant disabilities as a result of NHS systems. I now going to explore the possibility of setting-up an urgent DMT assessment clinic to try an avoid this from happening again.