Watchful Waiting

Barts-MS rose-tinted-odometer  ★ ★ ★ ★ ★

I have tried to include all the necessary information on MS DMT treatment decision-making into one easy to use and understand infographic. This infographic explains that when you see a patient with MS you have to decide if they have inactive MS or active MS. If they are active you have to decide how active their MS is (active vs. highly-active vs. rapidly-evolving severe MS). 

You then have to decide on the best treatment approach, i.e. the conventional step-care approach, rapid escalation or flipping the pyramid. To achieve this you need to profile patients into whether or not they have a good, intermediate or poor prognostic profile. Finally, you choose a treatment target, i.e. NEDA-2, NEDA-3, NED-4 or -5, or beyond. 

When I prepared this slide I had a debate with myself about whether or not I should leave off the ‘watchful waiting’ approach, but decided that there may be a place for it for people with inactive MS with a very good prognostic profile. And to be honest with you I have several patients in my own practice who for whatever reason we have adopted a watchful waiting approach. 

The good news is that there is a group of patients who do well with watchful waiting. In this Austrian study below, they looked at the outcome of a group of patients who in partnership with their HCPs had decided against DMTs. This group displayed features, which significantly differed from other patients; they tended to have a higher age at MS onset, were more likely to present with sensory symptoms, have a complete remission of symptoms and have a lower burden of disease on MRI. 

Importantly, watchful waiting in this group of patients seemed to work in that the decision not to start treatment was associated with a lower risk for conversion to secondary progressive MS. 

Interestingly, the group of patients who did not start a DMT against the advice of their HCP did much worse and had a 20% higher risk of converting to SPMS.

The moral of this story is that shared-decision making works and that patients should listen to what their HCPs think. Or HCPs should develop their communication skills explaining why DMTs are beneficial to some, but not all, pwMS. 

Bsteh et al. To treat or not to treat: Sequential individualized treatment evaluation in relapsing multiple sclerosis. Mult Scler Relat Disord. 2019 Dec 23;39:101908.

BACKGROUND: The frequency and long-term prognosis of relapsing multiple sclerosis (RMS) never receiving disease-modifying treatment (DMT) is unclear.

METHODS: We included 1186 RMS patients with a mean of 17.4 years follow-up and divided them into patients treated with any DMT (DMT) and patients untreated by shared (USD) or patient-autonomous decision (UAD).

RESULTS: The USD group displayed features, which significantly differed from the two other groups: higher age at onset, mainly sensory onset symptoms, complete remission of onset symptoms, less T2 and contrast-enhancing T1 lesions on initial brain MRI. In a multivariate cox regression, USD was associated with lower risk for secondary progression (SPMS) conversion (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.55-0.97, p = 0.011) compared to DMT, while UAD was associated with an increased SPMS conversion risk only in the “McDonald era” (HR 1.19, CI 1.02-1.58, p = 0.028).

CONCLUSION: Apart from the doubtless substantial improvement of the overall prognosis of RMS by DMT, it seems likely that not every patient necessarily needs immediate or even “hard and early” treatment. A “watchful waiting” approach with continuous clinical evaluation might be instead a viable option in RMS patients with favorable prognostic features at onset.

CoI: multiple

The next generation

Training the next generation of MSologists is one of my priorities.

I helped arrange and teach on the Pan-London Calman Specialist Registrar (SpR) teaching day yesterday. It was great to see so many young trainee neurologists attending; thank you. And to the speakers for giving up their time to teach and inspire the next generation of neurologists to become MSologists; thank you.

I hope you all enjoyed the day the following is the programme.

Neuro-Calman-MS-programme-16th-Jan-2019-gg3

I was impressed by the level of engagement of the audience. I was particularly happy with an insight from one of the trainees who suggested we should be managing MS they way rheumatologists manage RA; i.e. early and aggressively. This was music to my ears. I have been pushing the treat-2-target RA paradigm for MS for several years now. The only difference is that our treatment targets have gradually become more ambitious as we have moved from NEDA-1 (relapses) to NEDA-3 (MRI activity) to preventing end-organ damage as measured with MRI (normalising the rate of brain volume loss or NEDA-4) and normalising CSF and blood neurofilament levels (NEDA-5) and beyond. What I mean by beyond is that our ultimate aim is to cure people of having MS and to allow them to get to old age with as much brain as possible. Is this too ambitious?

The following is my presentation from yesterday that can be downloaded from my slideshare site.

At the end of my session, we got into a lively debate about whether or not everyone with MS needs to be treated. Obviously not, based on my presentation only people with active MS are eligible for treatment. Those who have inactive MS cannot be treated under current NHS England guidelines and if they remain inactive they will hopefully end-up having benign MS. Surely the aim of our treatments is to convert everyone with MS into having inactive MS that will hopefully turn out to be benign MS after 25-30 years of follow-up. What we did not cover in this mini-debate is what is active MS? Should it include smouldering MS?

If any of the trainees are reading this post can I please recommend that you read the following posts I have recently done and to bookmark my MS-Selfie site that is still under development.

Posts of potential interest:

  1. Why do MSers get worse despite being NEDA?
  2. Can we cure MS?
  3. Sequential therapies
  4. MS-relatedd fatigue
  5. Food Coma
  6. What the eye doesn’t see?
  7. MMR: to test or not to test?
  8. Radiologically isolated syndrome
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