Long-term Disability Outcomes in Teriflunomide-Treated Patients in TEMSO and TOWER: An Analysis Utilizing the Topographical Model of MS (P6.374)
Notice bibliographique
Résumé
Objective: To assess long-term disability outcomes and influence of relapses in a pooled analysis of the TEMSO/TOWER core and extension studies. Background: In both phase 3 clinical trials (TEMSO, NCT00134563; TOWER, NCT00751881), teriflunomide significantly reduced the risk of disability worsening confirmed for ≥12 weeks in patients with relapsing forms of MS. Design/Methods: Disability worsening was assessed using the Expanded Disability Status Scale (EDSS) and individual Functional System (FS) scores in patients treated with teriflunomide 14mg in the TEMSO and TOWER core and extension studies (TEMSO extension, NCT00803049). In this analysis, EDSS and FS scores were categorized based on change over 1 year as stable/improved (stable: change from baseline of ±0.5 [EDSS] or 0 [EDSS and FS] points; improved: ≥1-point reduction from baseline) or worsened (≥1-point increase from baseline). Scores were also categorized according to prior relapses. Results: A high proportion of patients had stable/improved EDSS scores (73.6%) over 5 years of treatment with teriflunomide 14mg. Individual FS scores also remained stable over 5 years. Mean EDSS scores were higher in patients who experienced relapse vs those who did not (Year 5: with relapse, 2.70; without relapse, 2.43). Consistent with these observations, scores were also higher in patients experiencing relapse in 5 of 7 reported FS (Year 5: with relapse, without relapse: Brainstem: 0.61, 0.54; Bowel and Bladder: 0.67, 0.63; Cerebellar: 1.07, 0.92; Pyramidal: 1.60, 1.38; Sensory: 1.10, 1.00). Conclusions: Long-term disability (measured by EDSS) remained stable in the majority of teriflunomide-treated patients over the combined study period, with a tendency for scores to be higher in patients experiencing relapse. Disability outcomes measured by FS scores were consistent with EDSS outcomes observed in the clinical development program. Data will be discussed utilizing principles of the topographical model of MS to analyze how the admixture of relapse and progression yields disability accumulation in this population. Study Supported by: Sanofi. Disclosure: Dr. Krieger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with acorda, bayer, biogen, emd serono, genentech, genzyme, mallinckrodt, medday, novartis, teva, and tg therapeutics. Dr. Freedman has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen, Canada Innovation, Chugai, Clene Nanomedicine, EMD Canada, Hoffman-La Roche, Merck Serono, Novartis, Opexa, Sanofi Aventis, Sanofi Genzyme, and Teva. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Accordant Health Services (Caremark), Adama, BiogenIdec, Celgene, Genzyme/Sanofi, Mallinckrodt, Mapi-Pharma, Novartis, Roche/Genentech. Dr. Truffinet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Truffinet has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Thangavelu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Thangavelu has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Mandel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi, with ownership interest. Dr. Mandel has received compensation for serving on the Board of Directors of Employee of Sanofi, with ownership interest. Dr. Lublin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and advisory boards: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; F. Hoffmann-La Roche/Genentech; MedImmune; Receptos/Celgene; Forward Pharma; Akros; TG Therapeutics; Abbvie; Rege. Dr. Lublin has received personal compensation in an editorial capacity for Co-Chief Editor of Multiple Sclerosis and Related Disorders. Dr. Lublin has received research support from Research funding from: Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; Transparency Life Sciences; NIH; NMSS.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,007 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,008 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».