Is it time to slay the Gambler's dilemma?

At a teaching session last week I presented several slides showing that at a population level rapid escalation (vertical switching) or flipping the pyramid (high-efficacy first-line) are really the only two treatment options we should be using to maximise life-long brain health of people with MS (pwMS). I also have little doubt that flipping the pyramid will also prove to be better than rapid escalation; there is some early data to support this and at least two clinical trials ongoing to address this.

The study below shows vertical switching  (low/moderate to high efficacy switching) is superior to horizontal switching (between low/moderate efficacy DMTs). 

The issue we debated on the teaching course is that as neurologists we don't treat populations, but individuals with MS and hence patient choice should always trump data like this. I explained to the audience that they must be careful not to share their patient's biases, i.e. the gambler's dilemma.  A gambler never goes into a casino to lose money. However, the gambler knows that on average he/she will lose money. The cognitive bias here is that they will be the lucky one that will win. Someone with MS is never going to have bad MS, they are always going to be the one that ends up with no problems in the future, therefore, they don't need more effective treatments. This is wrong. Given sufficient time MS causes disability in the majority of people with MS. Time is brain and brain lost is never regained. Therefore the practices of watchful waiting (a British medical tradition) and slow stepwise escalation comes at a cost to individuals and populations of individuals with MS. 

Can I suggest to counteract these cognitive biases you play a little game and imagine how you would treat yourself if you had MS? 

The treatment targets in MS have evolved from simply reducing the frequency of relapses (NEDA-0), to becoming relapse-free (NEDA-1) to having no measurable disease activity (NEDA-3), to preventing end-organ damage (NEDA4 and NEDA-5) to finally maximising brain health to allow our patients with MS so that they can age normally. In the future, we will want to cure our patients with MS before any meaningful damage is done to their brains and spinal cords, and we will want to prevent MS in people at risk of getting MS. To achieve these latter targets we need a much more proactive treatment approach and we also need to manage MS holistically, which includes actively managing comorbidities and focusing on wellness and lifestyle factors.

Is it time to slay the Gambler's dilemma? 

You can download these slides via the new ProfG's SlideShare site that I now control myself. Please feel free to use the slides. 

Chalmer et al. Treatment escalation leads to fewer relapses compared with switching to another moderately effective therapy. J Neurol. 2018 Dec 4. doi: 10.1007/s00415-018-9126-y.

BACKGROUND: Patients with multiple sclerosis who experience disease breakthrough often switch disease-modifying therapy (DMT).

OBJECTIVE: To compare treatment effectiveness of switch to highly effective DMT (heDMT) with switch to moderately effective DMT (meDMT) for patients who switch due to disease breakthrough defined as at least one relapse within 12 months of their treatment switch.

METHODS: We retrieved data from The Danish Multiple Sclerosis Registry on all relapsing-remitting MS patients with expanded disability status scale (EDSS) less than 6 who experienced disease breakthrough. We used propensity score matching to compare annualized relapse rates (ARRs), time to first confirmed relapse, time to first confirmed EDSS worsening and time to first confirmed EDSS improvement.

RESULTS: Each matched group comprised 404 patients. Median follow-up time was 3.2 years [interquartile range (IQR) 1.7-5.8]. ARRs were 0.22 (0.19-0.27) with heDMT and 0.32 (IQR 0.28-0.37) with meDMT; relapse rate ratio was 0.70 (95% CI 0.56-0.86; p = 0.001). Escalation to heDMT reduced the hazard of reaching a first relapse (HR 0.65; 95% CI 0.53-0.80; p < 0.001). We found no evidence of delayed disability worsening (HR 0.83; 95% CI 0.62-1.10; p = 0.20) and weak evidence of disability improvement (HR 1.33; 95% CI 1.00-1.76; p = 0.05) with heDMT.

CONCLUSION: Switching to heDMT is associated with reduced ARR and delay of first relapse compared with switching to meDMT. Patients on DMT who experience relapses should escalate therapy to heDMT.

CoI: multiple