Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis

Abstract

Background Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. Methods We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. Results Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. Conclusion Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

“…Also, 3% of the patients exposed to siponimod experienced bradyarrhythmia (including sinus node dysfunction) compared to 0.4% of those who received placebo 107 . There is paucity of real‐world evidence on siponimod regarding its safety profile; a recent publication by Regner‐Nelke et al showed that although that the second cause of adverse events in this cohort was cardiovascular (mainly hypertension), they did not describe bradycardia or cardiac conduction abnormalities 108 …”

“…107 There is paucity of realworld evidence on siponimod regarding its safety profile; a recent publication by Regner-Nelke et al showed that although that the second cause of adverse events in this cohort was cardiovascular (mainly hypertension), they did not describe bradycardia or cardiac conduction abnormalities. 108 Three types of S1P receptors can be found in the heart: S1P1, S1P2 and S1P3. 109 Stimulating these receptors in myocytes and nodal sinus is thought to produce bradycardia and decreased contractility.…”

Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme

“…Again, while this does not directly correlate with treatment cessation, because it is possible that these participants ceased to use MSGo while continuing siponimod treatment, they are not dissimilar to the cessation rate of 31% observed amongst pwSPMS treated with siponimod in Germany over an 18-month period. 17 The exploration of relative onboarding time and adherence rates was limited by the lack of participant numbers in some sub-groups, most notably the fingolimod switch group. Utilising dose self-reporting data in the real world may provide an estimate of true adherence, but in this case, it was hampered by a high proportion of opt-outs for reminders during maintenance.…”

“…19 Similarly, real-world data from a German cohort of 227 pwSPMS treated with siponimod report a mean age of 53.4 years, but a slightly lower female preponderance (56%). 17 In a German registry-based study designed to examine the characteristics of pwSPMS, 70% were female, the mean age at visit was 57.6 years and only 5% had previously been treated with fingolimod. 20 This is further reinforced in registry data showing an average age for SPMS conversion of 51.7 to 57.9 years depending on the classification method used.…”

Title: The need for a closer monitoring of novel drugs in MS: a Siponimod retrospective cohort study (Realhes Study)

“…Our ndings are consistent with reports across Europe of higher rates of lymphopenia and discontinuations due to AEs, in patients initially prescribed siponimod. 13,14 This has raised concerns given their clinical implications for the clinical management, including the increased risk of relapsed associated with dose reductions and dose discontinuations.…”