Dynamic scoring system aids decision to switch MS-therapies early

A newly developed dynamic scoring system can be used to support the decision whether or not to switch at an early stage from first- to second-line therapy.

Early identification of suboptimal response could prevent irreversible disability progression

The number of available disease-modifying treatments (DMTs) for the treatment of relapsing-remitting MS (RRMS) still increases. Early identification of suboptimal response could prevent irreversible disability progression by timely switching from a first-line to a more potent second-line DMT. With this in mind, a French group of researchers developed a dynamic scoring system to aid the early decision of switching therapies.

They had to 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 (PS). The main outcome measure was time to first relapse after matching.

The cohort was divided at random into a learning sample (n=8549) and a validation sample (n=4274). To compute the PS and to match patients, in a first ECT (n=2028) a frailty Cox model was set up that could predict the time to relapse in the patients who switched (n=1014) versus those who did not (n=1014).

iHR of relapse in case of switch versus waiting was established

The validation of the scoring system was performed by two additional ECTs from independent patients. In this ECT, the switch benefit was higher for patients who:

• Were younger at disease onset
• Had a low EDSS (≤5) at first-line treatment initiation
• Had ≥1 relapse under first-line treatment
• Had ≥1 Gd-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, with a cut-off value of 0.69. Patients with iHR ≤0.69 significantly benefited from a switch, patients with iHR >0.69 did not. This dynamic 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 (0.32—0.51) in switchers. In a second validation ECT of 518 patients with iHR >0.69, five-year relapse-free survival was 0.37 (0.30—0.46) and 0.44 (0.37—0.52), respectively, a non-significant difference.