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Effect of baseline age on efficacy and safety of Siponimod in patients with active secondary progressive multiple sclerosis


Siponimod ( Mayzent ) is a selective sphingosine 1-phosphate receptor ( S1P1 and S1P5 ) modulator, approved in the USA for treatment of relapsing forms of multiple sclerosis ( MS ), including clinically isolated syndrome, relapsing-remitting multiple sclerosis and active secondary progressive multiple sclerosis ( SPMS ).

In the phase 3 EXPAND registration trial in SPMS, Siponimod has significantly reduced risk of 3 month ( primary endpoint ) and 6 month confirmed disability progression ( CDP ) by 21% and 26%, respectively.

The objective of a study was to assess efficacy and safety of Siponimod in patients with active SPMS in subgroups of patients aged less than 45 and greater than or equal to 45 years ( median value ) at baseline.

Post hoc analyses were performed in subgroups of patients with active SPMS, defined as a relapse in the 2 years before screening and/or greater than or equal to 1 T1 gadolinium-enhancing lesion at baseline, randomized to Siponimod 2 mg daily or placebo.

Efficacy endpoints included: time to 3 and 6 month CDP ( as per Expanded Disability Status Scale scores ).
Adverse events, serious adverse events, and adverse events leading to treatment discontinuation were also assessed.

There were 779 patients with active SPMS: 306 patients aged less than 45 years ( Siponimod, n=213; placebo, n=93 ) and 473 patients aged greater than or equal to 45 years ( Siponimod, n=303; placebo, n=170 ).

In those less than 45 years, Siponimod has reduced risk of 3 month CDP by 31.9% compared with placebo ( Siponimod, n=57 [ 26.8% ]; placebo, n=35 [ 37.6% ]; hazard ratio [ HR ], [ 95% confidence interval ( CI ) ]: 0.68, [ 0.45, 1.04 ]; p=0.0734 ), and reduced 6 month CDP risk by 39.5% ( Siponimod, n=44 [ 20.7% ]; placebo, n=30 [ 32.3% ]; HR, [ 95% CI ]: 0.61, [ 0.38, 0.96 ]; p=0.0339 ).

In the subgroup of patients greater than or equal to 45 years, Siponimod has reduced the risk of 3 month and 6 month CDP by 31.5% and 33.1%, respectively, versus placebo ( 3 month: Siponimod, n=72 [ 23.8% ]; placebo, n=56 [ 32.9% ]; HR, [ 95% CI ]: 0.69, [ 0.48, 0.97 ]; p=0.0340; 6 month: Siponimod, n=55 [ 18.2% ]; placebo, n=44 [ 25.9% ]; HR, [ 95% CI ]: 0.67, [ 0.45, 1.0 ]; p=0.0471 ).

Siponimod was generally well tolerated in both subgroups. Rates of any adverse effects were similar for Siponimod and placebo in patients less than 45 years ( 82.6% vs 82.8% ), and slightly higher for Siponimod in those greater than or equal to 45 years ( 89.8% vs 75.9% ).
Rates of adverse effects and adverse effects leading to discontinuation were similar between groups.

In conclusion, in EXPAND, Siponimod has provided similar clinical effects in reducing CDP risk in patients aged less than 45 years and greater than or equal to 45 years with active secondary progressive multiple sclerosis. ( Xagena )

Source: ACTRIMS ( Americas Committee for Treatment and Research in Multiple Sclerosis ) Forum 2020

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