PARIS—Siponimod significantly reduces MRI activity and slows brain volume loss in patients with secondary progressive multiple sclerosis (MS), according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Effects are observable at month 12 and sustained at month 24. “These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with secondary progressive MS,” said Robert Fox, MD, a researcher at the Mellen Center for Treatment and Research in MS in the Cleveland Clinic, and colleagues.
Robert Fox, MD
The EXPAND study demonstrated the benefits of siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, on confirmed disability progression. Dr. Fox and colleagues examined these data to evaluate the effect of siponimod versus placebo on predefined MRI outcomes in patients with secondary progressive MS.
The researchers randomized patients 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter. Radiologists at a central reading center analyzed the scans. Key MRI outcomes included T2 lesion volume, number of new or enlarging T2 lesions, number of gadolinium-enhancing lesions, and brain volume loss assessed by percent brain volume change.
The full analysis set comprised patients who received one or more doses of study drug as per original randomization. The per-protocol analysis set consisted of all full-analysis-set patients without major protocol deviations and included efficacy data only up to discontinuation of double-blinded treatment.
The investigators randomized 1,651 patients. A total of 1,099 patients received siponimod (2 mg), and 546 received placebo. Dr. Fox and colleagues observed treatment benefits in favor of siponimod for all key outcomes and analysis sets investigated. Post-baseline MRI data were available for more than 80% of participants.
At month 12, the adjusted mean differences in the change in T2 lesion volume from baseline versus placebo were −613 mm3 in the full analysis set and −634 mm3 in the per protocol analysis set. At month 24, the differences were −778 mm3 in the full analysis set and −830 mm3 in the per protocol analysis set.
At month 12, the adjusted mean differences in percent brain volume change were 0.175 in the full analysis set and 0.221 in the per protocol analysis set. At month 24, the differences were 0.128 in the full analysis set and 0.277 in the per protocol analysis set.
Siponimod reduced the average T1 gadolinium-enhancing lesion count over months 12 and 24 by 86.6% in the full analysis set and 91.1% in the per protocol analysis set. Siponimod reduced the average count of new or enlarging T2 lesions by 80.6% in the full analysis set and 85.3% in the per protocol analysis set.
This study was funded by Novartis Pharma, which is headquartered in Basel, Switzerland.