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In the phase 3 EXPAND study, siponimod reduced the risk of 3-month confirmed disability progression by 21% compared with placebo and slowed the rate of brain volume loss over 12 and 24 months in people with SPMS [258]

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3 The risk factors for methotrexate AEs include higher doses (3.5 g/m 2 ), rapid infusions, preexisting kidney impairment, older age (aged 50 years), and the concurrent use of medications that are nephrotoxic or that impair methotrexate clearance (eg, proton pump inhibitors, aminoglycosides, nonsteroidal anti-inflammatory drugs, penicillin and penicillin derivatives, amphotericin, probenecid)

Scientific Reports 6(1):30010

In addition, the formulation failed to increase plasma concentrations compared to standard vitamin C [28]