Case study: a patronizing neurologist
When a neurologist thinks alemtuzumab is too risky the question needs to be asked ‘too risky for whom; the neurologist or the patient?’.
Case study
Do I have a small window of opportunity to influence the trajectory of my MS and to reduce my chance of SPMS in the future?
Overview
52-year-old female. No co-morbidities. No previous symptoms of MS. Currently fit and healthy, non-smoker, not on any other medication except HRT (started after one of your newsletters!). I do a lot of walking and cycling and am starting to run again (having stopped after the onset of MS).
Summary of MS onset
Jan 2021: Numb right hand came on over 48 hours, followed by an altered sensation of the skin in the right arm with nerve pain in the arm at night.
All resolved with the exception of my thumb which remains numb but still seems to be improving, and occasional tightness in my hand if I am tired.
Feb 2021: L’hermittes with vibrations in my right leg when I walked. All of this has been resolved. MRI of the cervical and thoracic spine showed one C-spine lesion in a place likely to cause this problem (and most likely my numb hand problem).
March 2021: MRI of the brain showed multiple non-enhancing lesions described by the radiologist as a ‘moderate’ disease burden. A non-MS neurologist told me it was most likely MS, that it had been there for a number of years and that I have brain atrophy (no mention how bad it was). I then saw an MS neurologist who disagreed and said that it is not possible to know when the lesions originated and wouldn’t diagnose MS as it was a single episode. MS neurologist refused to prescribe any drugs to reduce the chance of conversion to MS (NHS England guidelines used as a justification).
April 2021: Electrical sensations down my left-hand side. Occasional nerve pain on LHS but manageable and has improved with time. MS neurologist officially diagnosed MS and classed this as another relapse.
May 2021: Appointment with the neurologist to discuss DMT. I request to be treated with alemtuzumab (having looked at the data and understand the risks associated with it), my neurologist won’t discuss it due to risk (raises cardiovascular risk as his reason) and is adamant that he is not willing to prescribe it. I raise concerns about poor prognostic factors, (multiple brain lesions and brain atrophy as mentioned by the non-MS neurologist) and he disagrees with that and says that there are good prognostic factors (being female and attacks being sensory, also I think my neuro exam was normal).
June 2021: Onset of dizziness when walking and burning in the LHS of face, ear and eye, feeling weak and very ill, fatigue, and brain fog (I stopped working for a couple of weeks). The dizziness comes back when I am tired but otherwise, this seems to have resolved.
July and Aug 2021: three infusions of Natalizumab
Current situation: I have had 3 infusions of natalizumab, and the plan is to continue with this. Since starting natalizumab I have improved greatly, no new relapses, feeling well again, life has returned to normal, and any problems that currently remain are minor and manageable. So far natalizumab seems to be working well for me. I believe I made the right decision at the time to go onto natalizumab ASAP, I was relapsing every 8 weeks, feeling extremely ill, so needed treatment fast and was clearly not going to get alemtuzumab.
But my dilemma: At 52 do you think I have a short window of opportunity to influence the trajectory of my MS and reduce the chance of SPMS?
Do you think I should be trying to switch onto alemtuzumab or stay on natalizumab for as long as possible if it is proving to be effective? In addition, maximise lifestyle factors and consider clinical trials for add-on therapies (although I would do this anyway).
Are you seeing much better long-term outcomes with alemtuzumab compared to natalizumab with your patients? For me it’s tempting to carry on with natalizumab as I feel well now and that it is working so far, however, there is no knowing how long I can remain on it; I don’t want to have regrets in the future!
Technicalities: If you think it is worth switching, I assume I would want to do this ASAP because if I became stable on natalizumab for over a year I wouldn’t fit the licensing/NICE criteria for alemtuzumab?
I am currently JC– but if I become high JC+ I may need to come off natalizumab I assume at that point I would not qualify for an IRT if I have no active disease?
If you think it is worth moving to alemtuzumab do you have advice on how to go about it? I don’t believe a second opinion would persuade my neurologist to prescribe alemtuzumab so I would need to switch teams or hospitals. Just wondering how this works within the NHS?
Prof G’s Opinion
Based on your history and MRI findings the diagnosis of MS seems reasonable. I would say that based on your relapse rate and MRI findings you would be in a poor prognostic category (age, relapse rate, reasonably high lesion load, brain volume loss, spinal cord lesions and brainstem symptoms).
Your disease activity would put you in the rapidly evolving severe activity bracket, i.e. two disabling attacks in a 12 month period with MRI evidence of disease activity (increased T2 lesion load).
Based on this it seems reasonable that you were offered a high-efficacy DMT first-line. However, I disagree with your consultant neurologist’s opinion that you are not eligible for alemtuzumab based on your age and cardiovascular risk. In the CARE-MS1 and CARE-MS2, age cut-offs were 50 and 55 years respectively. At 52 you are not too old for alemtuzumab.
Why did he say you have an increased cardiovascular risk? Did he calculate your Q-risk 3 score? If so what is it? Did he recommend a statin, low-dose aspirin, antihypertensives, diet, exercise, etc.? It is one thing telling you that you have a high cardiovascular risk, but it borders on negligence to do nothing about it.
It is clear that natalizumab is very effective in rendering pwMS NEIDA (no evident inflammatory disease activity), but it is not as good as alemtuzumab or AHSCT at switching off smouldering MS, i.e. progression independent of relapses and slowing down brain volume loss into the normal range for age. In addition, the recovery of function is well described with natalizumab, but it is not quite at the same level on average as with alemtuzumab or AHSCT. In my tiering system of DMTs natalizumab is high efficacy and alemtuzumab and AHSCT are very high efficacy.
So yes, I would support your decision to switch from natalizumab to alemtuzumab. I have done this quite frequently in the past. Provided you sign-up to monitoring and understand the risks of alemtuzumab I see no reason why you should not be treated with alemtuzumab.
I am not sure if you are aware that if you are eligible for NICE-approved DMTs such as alemtuzumab the NHS, i.e. your consultant neurologist, has a legal obligation to offer it to you. Maybe you should make him aware of legislation that created NICE. The reason for this legislation was to prevent post-code prescribing which is what you have unfortunately been subjected to. Having to move MS centres to access alemtuzumab is exactly the reason why NICE was set up. Saying this you need to have a good and trusting relationship with your neurologist. If your relationship has broken down you have the option of asking to be managed by someone else in the Department or to be referred to another MS centre. The option of requesting and having a second opinion is enshrined in the NHS charter.
The attitude that the neurologist thinks alemtuzumab is too risky to be used as an MS treatment is very patronizing. The question that needs to be asked is ‘too risky for whom; the neurologist or the patient?’. We live in an era where the patient has as much access to information as HCPs. Why should patients not be involved in the decision-making about their treatment?
Whether or not alemtuzumab will prevent you from becoming secondary progressive in the future is a moot point. I would however make the point that you are less likely to become secondary progressive with alemtuzumab treatment than with natalizumab.; this is supported by a recent MS-Base real-world study (see Brown et al. JAMA. 2019 Jan 15;321(2):175-187.)
If you go onto fail natalizumab, i.e. have a relapse or new lesions on MRI, you would also be eligible for AHSCT under our London AHSCT guidelines and you would eligible for the StarMS trial. In the latter, you would be randomised to AHSCT or Alemtuzumab. I would urge you to consider participating in this trial.
I hope this helps.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.
Great article and interesting that most 'subjects' are pursuing the Alemtuzumab or HSCT route. On these, what is the theory behind halting the progression to SPMS and are there any studies that have tested this over a long period? is the data for HSCT different from Alemtuzumab on this particular disease marker?
I'm surprised to read that you consider NICE guidelines to be legal obligations! What about the times when it says you can't prescribe? As professionals do we not retain our right to treat according to our opinion and conscience, referring on to another specialist if need be? I do not think that a NICE determination compels me to produce a prescription.