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The consequences of not treating MS
Are there valid reasons not to treat MS with a disease-modifying therapy? What are the consequences of not treating MS? Is watchful waiting justified?
Many of my patients ask me what would happen to them if they didn’t go onto a DMT and how effective are DMTs at preventing these outcomes. In this Newsletter I try and address question 5 in my list of questions you need to ask yourself before starting a DMT.
Other questions to ask yourself before starting a DMT
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?
Risks of no DMT
If you are an individual with MS, predicting what will happen to you is difficult. However, lots of studies monitoring groups of pwMS show patterns in relation to the progression of the disease and its outcome, with various data sets being consistent.
Given sufficient time, pwMS who are not treated will become disabled. Most people focus on physical disability, but MS causes many hidden problems, such as cognitive impairment, anxiety and depression. The following set of infographics captures the headline results of what MS does to pwMS.
It is important to note that these outcomes are from the pre-DMT era and don't apply to populations of pwMS treated with DMTs. New real-life data indicates that DMTs, particularly high-efficacy DMTs, are preventing many of these problems. By not being on a DMT, if you have active MS, you are at risk of acquiring damage from focal inflammatory lesions. Early in the disease course, you may not be aware of this damage because of the remarkable capacity of the nervous system to compensate for damage. However, once the compensatory mechanisms have been exhausted, further damage results in overt disability. It is important to think about DMTs as being preventive treatments, i.e. the aim of the treatments is to delay, and hopefully prevent future disability.
Are there any reasons for not being treated with a DMT?
A large number of pwMS will not be on a DMT, for many reasons, including:
They may have inactive MS and hence will not be eligible for a DMT. Please be aware that there is no standard definition of what active MS is. To me, active MS is recent evidence of focal inflammatory disease activity defined as (a) clinical relapse(s) in the last 2 years or (b) MRI activity in the last 12 months (new or enlarging T2 lesions or T1 Gd-enhancing lesions) or (c) a raised CSF neurofilament light chain level in the last 12 months. Worsening disability without focal inflammatory disease activity is not active disease. Worsening disability in MS can be due to damage caused by past inflammation or the effects of premature ageing; anti-inflammatory DMTs can't address this problem. We need different types of DMTs to address these mechanisms, for example, neuroprotective and/or remyelination therapies and anti-ageing therapies.
In many situations, some neurologists think some pwMS will end up having benign disease and are only prepared to start treatment when these patients develop disability. I abhor this practice and is one of the reasons I spend so much of my time disseminating knowledge and getting involved with politics. Watchful waiting in terms of treating MS is not supported by data. It is clear that the early and more effectively you treat MS the better the outcome. The only situation I could condone watchful waiting is when the diagnosis of MS is in question. Sometimes in neurology time is the best diagnostician and if the person has MS it will declare itself with further disease activity which would be the trigger to start DMTs.
Trying to fall pregnant, pregnancy or breastfeeding are common reasons to interrupt or stop DMTs. Please note that most neurologists now have DMT options to treat MS during pregnancy so this is becoming a less common reason to not be on a DMT.
Some pwMS are not prepared to take the risks associated with DMTs.
Some pwMS don't believe in having their MS treated. It is not uncommon for some pwMS to want to try alternative medicines and turn down traditional DMTs. If you are one of these people I would recommend you continue to interact with your MS team and have regular monitoring (clinical, MRI, patient-related outcome measure or PROMS and possibly CSF) of your MS so that if these alternative strategies don't work you keep the option open of being treated with a 'traditional DMT'. A lot of alternative treatment strategies for MS are not incompatible with DMTs and hence should be viewed as being complementary. Understanding the difference between complementary and alternative treatments is important. Complementary treatment strategies are part of the holistic management of MS.
I some parts of the world MS DMTs not covered by a national health service or medical insurance scheme and some pwMS simply can't afford DMTs. Even in rich countries, some pwMS are disenfranchised and don’t have access to treatment, e.g. illegal immigrants, refugees and asylum seekers waiting for their applications to be processed. I recently received an email from a Syrian woman ask for me to help her sister who is currently living in a refugee camp in Turkey.
Progressive or more advanced MS
In most countries, neurologists don't initiate treatment in pwMS with more advanced MS. The latter is based on a lack of evidence of the effectiveness of DMTs in this population. Please note that we are increasingly offering pwMS with more advanced MS with active disease ocrelizumab (PPMS), siponimod (SPMS) or off-label therapies on a compassionate basis.
Some healthcare systems and some neurologists are reluctant to start DMTs in pwMS who are over a certain age. Again this is based on a lack of evidence of the effectiveness of DMTs in this population. I personally don't agree with this. This is why we need to do clinical trials in older populations of pwMS.
Many people have other medical problems which the treatment thereof take precedent over the treatment of MS. For example, a recent patient of mine was diagnosed with stage four bowel cancer. After her surgery, she had to start an intensive period of chemotherapy during which we stopped her DMT.
I am sure this list is not extensive, so if you have any other reasons to add why someone is not on a DMT please let me know and I will add them to the list.
I am encouraging readers to subscribe to the MS-Selfie Newsletter. The subscriptions will give you access to the case studies and the archive of these case studies. Please note all other newsletters, such as this one, are free. The money from subscriptions will be used to administer, transfer and curate the contents of the Newsletter onto a companion MS-Selfie microsite. The objective is to create an MS self-help guide.
The MS-Selfie case study from the 23rd of September is about a patient on ocrelizumab, who asked me whether or not she should delay her next dose of ocrelizumab to have the COVID-19 booster vaccine. She also wanted advice about which COVID-19 vaccine she should have for her booster.
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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.