Teriflunomide

證據等級: L5

預測適應症: 1 個

Teriflunomide: From No Registered Indication in Finland to Relapsing-Remitting Multiple Sclerosis

One-Sentence Summary

Teriflunomide (DrugBank DB08880) is not currently marketed in Finland, so no original approved indication is on record in the local regulatory database. The TxGNN model predicts it may be effective for Relapsing-Remitting Multiple Sclerosis (RRMS), with 28 clinical trials and 19 publications currently supporting this direction — notably, this is also teriflunomide's well-established indication in other markets (marketed elsewhere as Aubagio), so the model is largely recovering a known, extensively validated indication rather than proposing a novel one.

Quick Overview

Item	Content
Original Indication	Not available — no license or approved-indication record exists in Finland
Predicted New Indication	Relapsing-Remitting Multiple Sclerosis
TxGNN Prediction Score	99.24%
Evidence Level	L1
Finland Market Status	✗ Not Marketed (未上市)
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

The structured original_moa field for this drug is a data gap. However, the literature evidence in this pack does describe teriflunomide's mechanism: it is a selective, reversible inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which blocks de novo pyrimidine synthesis and reduces proliferation of activated T and B lymphocytes (PMID 31098896). This immunomodulatory mechanism is directly relevant to autoimmune, T/B-cell–mediated demyelinating disease such as MS.

Unlike a typical repurposing candidate, there is no distinct "original indication" to compare against here — the evidence pack shows zero Finland licenses and an empty original_indications field, meaning teriflunomide has simply never been registered in this market. Outside Finland, however, teriflunomide is a well-established, guideline-recommended first-line oral disease-modifying therapy for RRMS, a fact strongly corroborated by the trial and literature evidence below (including the pivotal TEMSO and TENERE Phase 3 trials, and its use as the active comparator in at least five subsequent Phase 3 trials against newer MS agents).

Because of this, the practical interpretation of this "candidate" is less a scientific discovery and more a market-registration gap: the mechanistic and clinical case for RRMS is already mature and extensively documented; what is missing is Finland-specific regulatory and safety documentation (see Data Gaps below), not proof of mechanistic plausibility.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00134563	Phase 3	Completed	1,088	Pivotal placebo-controlled RCT (TEMSO): teriflunomide reduced relapse frequency and delayed disability accumulation in relapsing MS
NCT00883337	Phase 3	Completed	324	TENERE: rater-blinded comparison of teriflunomide vs interferon beta-1a on time to treatment failure, relapse rate, fatigue and safety
NCT00803049	Phase 3	Completed	742	Long-term extension of EFC6049 documenting long-term safety/tolerability and durability of efficacy on disability and MRI outcomes
NCT04788615	Phase 3	Completed	185	Compared ofatumumab vs first-line DMT (including teriflunomide) in newly diagnosed relapsing MS
NCT07189325	Phase 3	Not yet recruiting	250	Non-inferiority trial of anti-CD20 maintenance vs de-escalation strategy in RRMS
NCT06663189	Phase 3	Not yet recruiting	200	TWINS: randomized withdrawal of DMTs (including teriflunomide) in inactive RRMS patients ≥55
NCT00273364	Phase 2	Completed	110	Hematopoietic stem cell therapy vs alternate approved therapy in inflammatory MS failing treatment
NCT00228163	Phase 2	Completed	147	Extension study assessing long-term safety and efficacy of teriflunomide in relapsing MS
NCT04129736	Phase 4	Completed	12	Determined teriflunomide serum and CSF concentrations at the 14 mg daily dose
NCT03464448	N/A	Completed	30	Mechanistic study of regulatory B lymphocytes as mediators of teriflunomide's therapeutic effect

Literature Evidence

PMID	Year	Type	Journal	Key Findings
32757523	2020	RCT	NEJM	ASCLEPIOS: ofatumumab vs teriflunomide head-to-head comparison in relapsing MS
40202623	2025	RCT	NEJM	Tolebrutinib (BTK inhibitor) vs teriflunomide in relapsing MS
36001711	2022	RCT	NEJM	Ublituximab vs teriflunomide in relapsing MS
39307151	2024	RCT	Lancet Neurology	evolutionRMS1/2: evobrutinib vs teriflunomide active-comparator Phase 3 trials
33779698	2021	RCT	JAMA Neurology	OPTIMUM: ponesimod vs teriflunomide in relapsing MS
37691530	2023	RCT (OLE)	Multiple Sclerosis Journal	ALITHIOS open-label extension: 4-year ofatumumab vs teriflunomide efficacy/safety
33620411	2021	Review	JAMA	Overview of MS diagnosis and treatment, including disease-modifying therapies
38174776	2024	Systematic Review	Cochrane Database Syst Rev	Network meta-analysis of immunomodulators/immunosuppressants for RRMS
31098896	2019	Review	Drugs	Comprehensive review of teriflunomide's mechanism, efficacy and safety in RRMS
37382446	2023	Review	Expert Rev Neurotherapeutics	Teriflunomide as first-line oral therapy in pediatric relapsing-remitting MS

Finland Market Information

Teriflunomide is not currently marketed in Finland — the evidence pack records 0 authorizations and no license entries. No Finland-specific product, dosage form, or approved-indication text is available.

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug-interaction data are all unavailable in the current evidence pack — the DDI query returned no records.)

Conclusion and Next Steps

Decision: Hold

Rationale: Efficacy evidence is exceptionally strong (L1) — two completed pivotal Phase 3 RCTs (TEMSO, TENERE) plus a long-term Phase 3 extension and five further Phase 3 head-to-head trials establish teriflunomide as a validated first-line RRMS therapy elsewhere. However, this candidate cannot advance to safety evaluation: the TFDA/Fimea package insert (warnings and contraindications) is a Blocking data gap, DDI data are absent, and the drug has zero current authorizations or market history in Finland.

To proceed, the following is needed:

TFDA/Fimea package insert — warnings and contraindications (Blocking gap, required before S1 safety review)
Structured DrugBank MOA record (High priority gap)
A drug-drug interaction dataset (current query returned no results)
Confirmation of Finland/EU regulatory pathway and timeline for market authorization
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.