Gaining First Insights on Secondary Progressive Multiple Sclerosis Patients Treated With Siponimod in Clinical Routine: Protocol of the Noninterventional Study AMASIA
Bibliographic record
Abstract
BACKGROUND: A high proportion of patients with relapsing remitting multiple sclerosis convert to secondary progressive multiple sclerosis (SPMS) characterized by irreversibly progressing disability and cognitive decline. Siponimod (Mayzent), a selective sphingosine-1-phosphate receptor modulator, was recently approved by the European Medicines Agency for the treatment of adult SPMS patients with active disease, as evidenced by relapses or magnetic resonance imaging features of ongoing inflammatory activity. Approval by the Food and Drug Administration covers a broader range of indications, comprising clinically isolated syndrome, relapsing remitting multiple sclerosis, and active SPMS. However, treatment effects of siponimod have not been assessed in a structured setting in clinical routine so far. OBJECTIVE: The objectives of AMASIA (impAct of Mayzent [siponimod] on secondAry progressive multiple Sclerosis patients in a long-term non-Interventional study in GermAny), a prospective noninterventional study, are to assess the long-term effectiveness and safety of siponimod in clinical routine and to evaluate the impact of disease burden on quality of life and socioeconomic conditions. Here, we report the study design of AMASIA. METHODS: Treatment effects of siponimod will be evaluated in 1500 SPMS patients during a 3-year observational phase. According to the genetic polymorphism of CYP2C9, the initial dose will be titrated to the maintenance dose of 1 mg (CYP2C9*1*3 and *2*3) or 2 mg (all other polymorphisms of CYP2C9 except *3*3, which is contraindicated) taken orally once daily. Primary endpoint is the 6-month confirmed disability progression, as assessed by a functional composite endpoint comprising the Expanded Disability Status Scale and symbol digit modalities test to take appropriate account of cognitive changes and increase sensitivity. Further measures including multiple sclerosis activity data; assessments of functional domains; questionnaires addressing the patients', physicians', and relatives' perspectives of disability progression; cognitive worsening; quality of life; and socioeconomic aspects will be documented using the multiple sclerosis documentation system MSDS3D. RESULTS: AMASIA is being conducted between February 2020 and February 2025 in up to 250 neurological centers in Germany. CONCLUSIONS: AMASIA will complement the pivotal phase III-derived efficacy and safety profile of siponimod with real-world data and will further evaluate several individual treatment aspects such as quality of life and socioeconomic conditions of patients and caregivers. It might help to establish siponimod as a promising option for the treatment of SPMS patients in clinical routine. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19598.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.009 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.004 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.019 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".