Prognostic Value of the Magnims Score for Assessment of Disease Modifying Therapy in Patients with Relapsing Multiple Sclerosis Treated with Ponesimod

Background: For patients (pts) with multiple sclerosis (MS), it is crucial for clinicians to understand long-term prognosis after beginning a new disease-modifying therapy (DMT) to decide whether treatment is working as intended. The Magnetic Resonance Imaging in MS (MAGNIMS) score uses the number of new or enlarging T2 lesions and relapses over one year to predict risk of disease worsening. Existing validation studies have shown the validity of the tool for several DMTs, but not in pts receiving ponesimod (PON).

Objectives: To assess the value of the MAGNIMS score in assessing potential suboptimal treatment response and prognostic effect on disability status in a large phase 3 clinical trial.

Methods: Patients with relapsing MS treated with PON 20 mg or teriflunomide (TER) 14 mg in the phase 3 OPTIMUM study were classified according to MAGNIMS score at week 60 (0, 1, or 2, with higher scores indicating worse clinical outcomes). The proportions of pts in each treatment arm were compared. Cox regression analysis was used to assess whether MAGNIMS score at week 60 could differentiate the risks of times to 12- and 24-week confirmed disability accumulation (CDA) at week 108 by pooling the two treatment arms.

Results: In analyzing the individual treatment arms, significantly more PON pts had a MAGNIMS score of 0 at week 60 relative to TER (57% vs 46%; odds ratio [OR] 1.56; p<0.001), while significantly fewer pts were classified as 2 in the PON arm (13% vs 20%; OR=0.59; p=0.002). To validate the prognostic effect of the MAGNIMS score, 1061 pts were pooled (n=533 for PON, n=528 for TER) and assigned a score, with 51%, 32%, and 17% pts scored as 0, 1, and 2, respectively. The risk of both 12- and 24-week CDA at 108 weeks were significantly different between the MAGNIMS score groups. For 12-week CDA, the hazard ratios (HRs) were 1.97 (p=0.002) for 1 vs 0 and 3.48 (p<0.001) for 2 vs 0, indicating that pts with a higher MAGNIMS score at week 60 had a higher risk of experiencing a 12-week CDA. For 24-week CDA, the HRs were similar, 1.99 (p=0.007) for 1 vs 0 and 4.14 (p<0.001), respectively for 2 vs 0.

Conclusions: These results further validate the potential of the MAGNIMS score to predict the long-term risk of disability worsening and its clinical value in early detection of pts with a suboptimal response to a newly initiated DMT. Treatment with PON resulted in more pts classified with a favorable MAGNIMS score at week 60 than TER, but long-term effects on CDA needs to be further confirmed in future research.