Watchful Waiting

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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

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

24 comments

  • Me being a pain in the rear end yet again: T2T we get. But NEDA4! Let alone NEDA5!

    This is like me running 5k one day and “targetting” ironman.

    I think hope is a scarce commodity that should be mamaged very carefully.

    • If you want to target NEDA-4 you need to flip the pyramid. The ability to normalise brain volume loss is not a job for the lower efficacy DMTs.

  • But watchful waiting should be proactive with regular MRI monitoring. A lot of neurologist send you away and expect you to come back on your own accord when you have new symptoms. This is passive watchful waiting and not to be recommended.

  • Always on the money, prof G. As a junior registrar deeply interested in MS, I found the infographic to be an excellent aide, together with the paper in which it was included originally. It really helps to follow some sort of guide in DMT choosing, at least in principle and especially when you are moving your first steps in patient management, all the more so as I fully and unapologetically share your vision on how to approach MS. Reading this blog every day is helping immensely. Thank you for your work!

  • Re
    To achieve this you need to profile patients into whether or not they have a good, intermediate or poor prognostic profile.

    How is this done? At diagnosis, what suggests good prognosis? And vice versa?

    Are you suggesting inactive PPMS is good prognosis and therefore not worth treating? I don’t think you are…. please explain further?

    Seems to me that ticking the boxes for highly active, rapidly evolving MS is lucky as you are offered the most effective treatments.

    Regulators love neat little boxes.

    MS is one disease not 1a, 1b, 1c, 2a, 2b, 3a, 3b

  • Missing here are two, important, factors: the patient’s lifestyle and his or her ability to accept risk. The method of administration of the DMT, for example, may be very important to someone with a full-time job or who is incapable of self-injecting. Risk tolerance may vary by age, comorbities or lifestyle.

    These should be a part of the patient-neuro treatment discussion.

  • Thanks, Prof G, this is very informative!
    What are your thoughts on watchful waiting for CIS patients? Do you use the same approach and prognostic criteria?

  • Interesting family history of MS not on here as a factor. I would think a strong family history of severe or terminal ms would be a point towards poorer prognostic indicator as well.

    Also I see age of diagnosis but not age of estimated onset? Some people are diagnosed at their first symptom, others have had symptoms ignored for years before finally taken seriously. Surely this should be taken into account when thinking about prognosis as well?

  • “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. ”

    What could be the reason for this?

      • I also think so. I would have hoped that such a statement would not have gotten past the reviewers and presented as a finding in the results and abstract.

        “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”

        I was surprised to see this statement echoed on this blog without a footnote or remark…

        “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.”

        Unfortunately, this is how fake news starts. I can already imagine the next headline: “Science reports: Forgoing DMT’s prevents conversion to SPMS”

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