Please note that I am so conflicted when it comes to giving advice about DMTs that you need to take what I say and think with a ‘pinch of salt’; including the contents of this post.
Meaning: To take something with a “grain of salt” or “pinch of salt” is an English language idiom that means to view something with scepticism or not to interpret something literally.
The endless churn or cycling of DMTs is creating problems for MSologists and their patients alike. I am increasingly seeing patients who have been on six or more DMTs. Why? Many switching decisions are related to tolerance issues, unacceptable adverse events, family planning and breakthrough disease activity. However, some churn sadly is due to unrealistic expectations, over- or under-stretched healthcare systems or simply fashion.
Let’s deal with unrealistic expectations. If you are on DMT x and you are NEDA 1&2, i.e. no relapses or new focal MRI activity, but are still getting worse many patients are being switched in the hope that a different DMT will get on top of smouldering MS. The reality is that we have no data on the efficacy of DMTs in this situation; in fact, we have data from more advanced MS trials that anti-inflammatory DMTs don’t actually make much difference to the pathology driving this stage of the disease. This is why we are pushing so hard for combination therapy trials and the oncologising of MS to create the infrastructure to run multiple, parallel, add-on trials to address smouldering MS.
Overstretched healthcare systems are incentivising their HCPs to switch patients onto treatments that are less of a burden to the healthcare system, i.e. less monitoring and less hassle for the neurologists and nurse specialists. I have seen this with many patients who are relatively low risk of PML on natalizumab who have been switched off natalizumab to another DMT without having the relative risks, nor the strategies we can use to lower the risk of PML explained to them. In addition, some of the switch therapies, in particular anti-CD20 therapies, come with undefined long-term risks of their own. One of the patients I saw in this situation wants to go back onto natalizumab as she does not feel ‘as well’ on an anti-CD20 as she did on natalizumab. She is complaining that her brain fog has returned. If she had had things explained to her I suspect she would not have switched-off natalizumab.
Switching as a result of under-stretched healthcare systems is the switching of patients onto treatments to increase clinical activity and hence profits. This is more common in fee-for-service healthcare systems but also occurs in the NHS. In short, if you want to maximise your income it is better to have patients on treatments that you can charge extra for, i.e. infusions, monitoring visits, etc. Neurologists are no different from other people; if you create a perverse incentive for doing something we neurologists respond to it, it is human nature.
Fashion refers to the trend that patients often want to be on the newest and coolest DMT. The trend for the latest, brightest and most expensive DMT is often driven by social media influencers; pwMS who promote officially or unofficially DMTs. Switching therapies based on these criteria is not ideal, but some neurologists give-in to their patient’s demands and switch treatments for no apparent treatment benefit. If you are doing well on one treatment moving to another DMT is no guarantee that you are necessarily going to do better on the new drug. In fact, the new treatment may be associated with adverse events and long-term complications that have yet to emerge (known-unknowns on unknown-unknowns).
When I push the early-diagnosis, early-treatment, high-efficacy-first-line, flipping-the-pyramid philosophy of treating MS, I know that some patients will be harmed for the benefit of the overall population of pwMS. The counter-argument is to maximise the safety of the individual by using a slower-escalation strategy. This strategy, however, comes at a cost for the overall population; i.e. a less favourable group outcome. The path between these two extremes is a narrow one and full of obstacles or cognitive biases that in my opinion get in the way of doing what is best for pwMS. What we can do as neurologists, regardless of what treatment philosophy we subscribe to, is to avoid unnecessary DMT churn.
Marangi et al. Changing therapeutic strategies and persistence to disease-modifying treatments in a population of multiple sclerosis patients from Veneto region, Italy. Mult Scler Relat Disord. 2020 Feb 10;41:102004.
BACKGROUND: The availability of new disease-modifying treatments (DMTs) in the last years has changed the therapeutic strategies used in Multiple Sclerosis (MS). We aimed to describe trend in DMTs utilization and persistence to treatment in a large sample of patients attending 10 MS centres from four provinces of Veneto, Italy.
METHODS: Demographic, clinical and DMTs information of patients regularly followed from January 2011 to August 2018 were recorded and analysed. Persistence at 12, 24 months and at last follow-up was assessed by Kaplan Meier survival analysis. Multivariable Cox- proportional hazard model was used to identify predictors of persistence.
RESULTS: Of 3025 MS patients 65.7% were in treatment al last follow-up. Dimethylfumarate (DMF) was the most prescribed single drug among first-line and fingolimod among second-line DMTs. In the cohort of 1391 cases starting any DMT since 2011 12.9% stopped within 6 months, 24% within 12 and 40.3% within 24 months. Disease duration > 5 years at therapy start was predictive of greater risk of discontinuation, while age and sex were not. DMF use was predictive of higher persistence at 12 and 24 months, but not at last follow-up when azathioprine and glatiramer acetate showed the highest persistence compared to other DMTs. Side effects represented the main reason of discontinuation.
CONCLUSION: The use of the new oral DMTs greatly increased since their approval but persistence in the long-term is not better than with old drugs. The treatment choice is still a challenge both for patients and their doctors.