Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) are demyelinated multiple sclerosis (MS) lesions with ongoing microglia/macrophage activity, resulting in irreversible neuronal damage and axonal loss. Evobrutinib is a highly selective, covalent, CNS-penetrant, Bruton tyrosine kinase inhibitor. This post hoc analysis evaluated the effect of evobrutinib on slowly expanding lesion (SEL) volume, an MRI marker of CALs, assessed baseline-week 48 in a phase 2, double-blind, randomized trial (NCT02975349) in relapsing MS (RMS). METHODS: ) over time. SELs were identified by MRI and assessed by the Jacobian determinant of the nonlinear deformation from baseline to week 48. SEL volume analysis, stratified by baseline T2 lesion volume tertiles, was based on week 48/end-of-treatment status (completers/non-completers). Treatment effect was analyzed using the stratified Hodges-Lehmann estimate of shift in distribution and stratified Wilcoxon rank-sum test. Comparisons of evobrutinib and DMF vs placebo/evobrutinib 25 mg QD were made. Subgroup analyses used pooled treatment groups (evobrutinib high dose [75 mg QD/BID] vs low dose [placebo/evobrutinib 25 mg QD]). RESULTS: = 0.011). SEL volume was significantly reduced for evobrutinib high vs low dose within baseline Expanded Disability Status Scale ≥3.5 and longer disease duration (≥8.5 years) subgroups. DISCUSSION: Evobrutinib reduced SEL volume in a dose-dependent manner in RMS, with a significant reduction with evobrutinib 75 mg BID. This is evident that evobrutinib affects brain lesions associated with chronic inflammation and tissue loss. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT02975349. Submitted to ClinicalTrials.gov on November 29, 2016. First patient enrolled: March 7, 2017. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that evobrutinib reduces the volume of SELs assessed on MRI comparing baseline with week 48, in patients with RMS.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".