Dynamic scoring system aids decision to switch MS therapies early

A newly developed dynamic scoring system has been developed and validated to support the decision of switching at an early stage from first-line to second-line MS therapies. Based on 5-year relapse-free survival, it was concluded that at least one-third of relapsing-remitting MS (RRMS) patients might benefit from an earlier switch [1].

Early identification of suboptimal response could prevent irreversible disability progression by timely switching from a first-line to a more potent second-line disease-modifying therapy (DMT) [2]. With this in mind, Dr Camille Sabathé (French Institute of Health and Medical Research, France) and colleagues developed a dynamic scoring system to aid the early decision of switching therapies. They had at their disposal a French cohort of 12,823 adult RRMS patients who had started a first-line treatment between 2008 and 2018. Patients who switched to a second-line treatment because of inefficacy were compared with patients remaining on first-line treatment, by use of a 1:1 emulated clinical trial (ECT) based on time-dependent propensity scores. The main outcome measure was time to first relapse after matching.

The cohort was divided at random into a learning sample (n=8,549) and a validation sample (n=4,274). To compute the propensity scores and to match patients, in a first ECT (n=2,028) a frailty Cox model was set up that could predict the time to relapse in the patients who switched (n=1,014) versus those who did not (n=1,014). The switch benefit was found to be higher for patients who:

• were younger at disease onset;
• had a low Expanded Disability Status Scale (EDSS) score (≤5) at first-line treatment initiation;
• had ≥1 relapse under first-line treatment;
• had ≥1 gadolinium-enhancing T1 lesion on MRI under first-line treatment.

Based on these outcomes, the individual hazard ratio (iHR) of relapse in case of switch versus waiting was established. Patients with iHR ≤0.69 significantly benefited from a switch, patients with iHR >0.69 did not. This scoring system was then applied on a first validation ECT of 348 patients with iHR ≤0.69. Five-year relapse-free survival was 0.14 (95% CI 0.09–0.22) in non-switchers and 0.40 (95% CI 0.32–0.51) in switchers. In a second validation ECT of 518 patients with iHR >0.69, 5-year relapse-free survival was 0.37 (95% CI 0.30–0.46) and 0.44 (95% CI 0.37–0.52), respectively, a non-significant difference.

1. Sabathé C, et al. Improving the decision to switch from first to second-line therapy in MS: a dynamic scoring system. OP035, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Ziemssen T, et al. Mult Scler Relat Disord. 2015;4(5):460–469.

 

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Posted on 9 December 202125 March 2024