The Efficacy of Alemtuzumab Is Maintained in Patients Who Develop Thyroid Adverse Events (P7.272)
Bibliographic record
Abstract
OBJECTIVE: To determine whether thyroid adverse events (AEs) impact alemtuzumab efficacy. BACKGROUND: Alemtuzumab showed superior efficacy over high-dose subcutaneous interferon beta-1a and manageable safety in relapsing-remitting multiple sclerosis (RRMS) patients in phase 3 CARE-MS studies; efficacy was sustained for 4 years in the extension study. Alemtuzumab’s consistent safety profile includes an identified risk of predominantly non-serious autoimmune thyroid disorders. DESIGN/METHODS: In the 2-year core studies, RRMS patients who were treatment-naive (CARE-MS I; NCT00530348) or relapsed on prior therapy (CARE-MS II; NCT00548405) received alemtuzumab 12 mg/day intravenous on 5 consecutive days at baseline and 3 consecutive days 12 months later, with as-needed alemtuzumab retreatment in the ongoing extension (NCT00930553). Sustained accumulation of disability (SAD) was defined as 蠅1-point Expanded Disability Status Scale score increase confirmed for 蠅6 months (蠅1.5-point if baseline score=0). Thyroid function testing was performed at baseline and quarterly using a comprehensive monitoring program. RESULTS: In core studies, 811 patients were treated with alemtuzumab; 742 (CARE-MS I, n=349; CARE-MS II, n=393) entered the extension. Over 4 years, 37.5[percnt] (CARE-MS I) and 34.7[percnt] (CARE-MS II) of patients experienced 蠅1 thyroid AE. Annualized relapse rates were similar between patients with vs without thyroid AEs (CARE-MS I: 0.15 vs 0.16, p=0.76; CARE-MS II: 0.22 vs 0.23, p=0.86). Patients experiencing thyroid AEs had a similar risk of relapse vs patients without thyroid AEs (CARE-MS I: hazard ratio [HR] 1.20, p=0.30; CARE-MS II: HR 1.00, p=0.97). Risk of SAD was similar between patients with vs without thyroid AEs (CARE-MS I: HR 1.38, p=0.21; CARE-MS II: HR 0.98, p=0.92). CONCLUSIONS: The occurrence of thyroid AEs did not increase the risk of relapse or SAD after alemtuzumab; the efficacy of alemtuzumab was maintained. These findings support the favorable benefit-risk profile of alemtuzumab in RRMS patients. Study Supported by: Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".