Long-term Disability Outcomes in Teriflunomide-Treated Patients in TEMSO and TOWER: An Analysis Utilizing the Topographical Model of MS (P6.374)
Bibliographic record
Abstract
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.
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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 | 0.007 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.008 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".