Medicine and neurology are an art and not a science, which explains why one neurologist or MS centre may say one thing and a second or third neurologist will say something else. I am acutely aware this causes confusion and is very frustrating for many people with MS.
“The practice of medicine is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head.” William Osler
I recently saw a patient for a second opinion who has been on ocrelizumab for over two years. She had previously been on dimethyl fumarate (DMF, Tecfidera) and had disease activity on DMF, which had prompted the switch to ocrelizumab. She has done well on ocrelizumab being relapse and MRI activity free (NEIDA), but since COVID-19 has highlighted safety issues around long-term anti-CD20 therapy, she is not happy about staying on ocrelizumab long-term. She had asked her local neurologist if she can switch to an IRT (immune reconstitution therapy) but was told as her MS is inactive she is not eligible and therefore she can’t switch. Do you agree with this?
I didn’t agree and we have offered her a switch to cladribine or alemtuzumab, by applying eligibility criteria for these two DMTs retrospectively, i.e. if she was eligible for cladribine or alemtuzumab when she was started on ocrelizumab she is now eligible for a switch from ocrelizumab to cladribine or alemtuzumab. She, however, is not eligible for AHSCT in London as she had not failed two DMTs, including a high efficacy DMT, prior to starting ocrelizumab.
The retrospective application of eligibility criteria, as used in this case, is not a universally accepted principle. I am interested to know if you agree with this principle?
Several issues that arise with this case are due to the fact that we don’t have a good evidence base on switching from ocrelizumab to an IRT. Do we wait for B-cell reconstitution before the switch? Is there a greater risk of persistent long-term B-cell depletion from an IRT post-ocrelizumab? If she chooses alemtuzumab do we switch immediately, while she is still B-cell depleted, hoping to reduce her risks of secondary autoimmunity? Will alemtuzumab have the same impact on brain volume loss and disability improvement post-ocrelizumab? It is for these reasons that we ask all of our patients to sign consent for the switch, in which we state we don’t have good safety and efficacy data on using an IRT after ocrelizumab and that the patient has to agree to the monitoring requirements associated with the relevant IRT they choose.
On the other side of the coin if enough pwMS switch from an anti-CD20 to an IRT we will collect enough real-life data to get a feel for what happens to these people long-term and whether or not any safety concerns emerge.
I think the guiding principle, in this case, and other cases like it, is being flexible and accommodating of the patient’s requirements throughout the course of their disease, but at the same time being mindful of the NHS England’s guidelines.
The following cartoon tries to explain the philosophy behind applying eligibility criteria retrospectively. Please be aware that in Europe and the UK there are four levels of MS disease activity that are used when deciding, which DMT a patient is eligible for. I would recommend reading my previous Newsletter ‘Are you eligible for an MS disease-modifying therapy?’ (6-Nov-2021) for specific information on this topic.
MS Disease activity classification
Inactive MS - not eligible for DMTs
Active MS - eligible for so-called platform therapies (interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate and ponesimod) and ocrelizumab or ofatumumab.
Highly active MS - eligible for all therapies except natalizumab. Please note in England fingolimod can only be used second-line.
Rapidly-evolving severe MS - eligible for all DMTs
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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.
The retrospectoscope