Summary
Knowing what type of MS you have and whether or not your MS is active or inactive will allow you to ask your MSologist questions about the kinds of MS treatment you are eligible for.
Questions to ask yourself before starting a DMT
What type of MS do I have?
What prognostic group do I fall into?
What is the risk of not being treated with a disease-modifying therapy (DMT)?
Am I eligible for treatment with a DMT?
What is the difference between a maintenance/escalation DMT and an IRT (immune reconstitution therapy)?
Do I understand the difference between short-term intermittent and long-term continuous immunosuppression?
Do I understand the concept of treat-2-target?
What are the attributes of the specific DMTs?
How can I derisk or reduce my chances of getting certain adverse events on specific DMTs?
Type of MS
You should be able to classify yourself as having either relapsing or non-relapsing progressive MS.
85-90% of pwMS start with so-called relapse onset MS, i.e. they have a definite attack that is usually followed by a period of recovery that can be complete or incomplete. When you have only one attack you may be labelled as having a clinically isolated syndrome (CIS). This means that you don't fulfil the current diagnostic criteria for having full-blown MS, but you are at risk of developing further attacks and hence MS in the future. Once you have more attacks, either clinically in the form of relapse or subclinically with new lesions on MRI, then you are usually diagnosed as having MS.
After a variable period of time, people with relapse-onset MS may notice worsening neurological function without improvement. When this occurs it is called secondary progressive MS (SPMS). Please note that SPMS can occur with or without superimposed relapses.
A small number of pwMS (10-15%) will present with worsening neurological function without a prior history of relapses. This type of MS is called primary progressive MS (PPMS). Interestingly, a number of people with PPMS go onto have relapses and these people have been referred to as having progressive-relapsing MS (PRMS).
Rarely someone may present with worsening neurological function, similar to PPMS, but have a prior history of just one relapse. This is referred to as single-attack progressive MS, but most MSologists classify these patients as having SPMS.
When we refer to people with relapsing MS the term captures all pwMS who are still having relapses, i.e. within the last 2 years, and includes people with RRMS, R-SPMS and PRMS. In comparison, non-relapsing progressive MS refers to SPMS and PPMS. These latter two groups of pwMS should have no history of recent relapses, i.e. in the last 2 years. To make things confusing non-relapsing progressive MS used to be referred to as chronic progressive MS (see below).
Why is this important? Different DMTs are licensed for different types of MS and many treatment guidelines specifically state the type of MS a particular drug can be used for. However, to be honest with you what is important is to know if your MS is active or inactive. Active MS responds to anti-inflammatory treatments and inactive MS is less responsive to currently licensed DMTs.
Is MS one or more diseases?
In the past MS was one disease, i.e. you either had MS or you did not have MS. The stages of MS were referred to as early relapsing MS or chronic progressive MS, but MS was still one disease.
However, when disease-modifying therapies were developed MS was split into multiple sub-types. The splitting of MS into multiple diseases was driven by commercial considerations and allowed interferon-beta to be licensed under the orphan-drug act in the United States. To be classed as an orphan disease there had to be less than 200,000 people diagnosed with the disease in the US. By dividing MS into relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and later clinically-isolated syndromes (CIS) ensured that each category had fewer than 200,000 people.
Since then progressive-relapsing (PRMS) and radiologically-isolated syndrome (RIS) categories have also been added as potential subtypes. These classifications tend to be arbitrary and overlap with each other and there is no biological basis to support MS as being more than one biological disease.
From a treatment perspective, it is more important to know if your disease is active. This means there is evidence of ongoing inflammation in the brain and spinal cord. If you are having relapses, or are developing new lesions on MRI, or you have raised neurofilament light levels (NFL) in your cerebrospinal fluid (CSF) or blood your MS is active.
Most people will accept that you have to have had a relapse in the last 2 years and/or have had MRI evidence of activity in the last 12 months and/or raised CSF NFL levels measured in the last 6 months to be called active.
Please note these definitions of activity are quite arbitrary and tend to have been set by the entry criteria for clinical trials of disease-modifying therapies, as a result, they tend to be incorporated into clinical guidelines. The general consensus is that if your MS is active you are likely to respond to anti-inflammatory therapies.
The term progressive MS is entrenched in the field and refers to the stage of MS when your disability gets worse independent of relapses and possibly focal inflammatory lesions. I say possibly because our current MRI scans don't report out the presence of new or enlarging microscopic lesions but only those that are larger than ~3-4 mm in size. NFL measurements in either the CSF or blood have the advantage of being additive and integrating inflammatory activity. In my experience about 1 in 10 patients who are called inactive based on clinical and MRI activity are active when analysing CSF NFL levels. The problem with the last category of MS activity that is based on raised neurofilament levels is that many MSologists, regulators and payers won’t accept this definition of MS disease activity as the tests for NFL levels is currently not widely available.
So arming yourself with the type of MS you have and whether or not your disease is active will allow you to ask your MSologist questions about the kinds of treatment you are eligible for.
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.
What can a neuro offer a patient with SPMS without relapses? There must be many patients in this position, but no licensed therapies. Can a neuro prescribe off-label treatments eg Simvastatin (which is in trial as a potential neuro-protective agent) or Metformin (which is in trial as a potential remyelination agent)?
So helpful, thank you.