Clinical and mechanistic effects of cladribine in relapsing multiple sclerosis: 2-year results from the MAGNIFY-MS Study
Bibliographic record
Abstract
Background: Cladribine, an oral prodrug, penetrates the blood-brain barrier, impacting biomarkers of disease progression within the central nervous system. Objectives: Describe disease activity in cladribine tablets (CladT)-treated people with highly active relapsing multiple sclerosis (pwRMS) using clinical outcomes and biomarkers. Design: MAGNIFY-MS was an open-label, single-arm, phase IV trial with four sub-studies. Participants were grouped by previous treatment (Tx); Tx-naïve versus Tx-experienced; those with previous exposure to second-line therapies were excluded. This analysis describes cerebrospinal fluid (CSF) and optical coherence tomography (OCT) sub-studies. CSF sub-study participants were stratified by the number of oligoclonal bands (OCBs) at baseline (≥2/≥4). Methods: Logistic regression analysis is reported for no evidence of disease activity (NEDA)-3 and no evidence of progression or active disease (NEPAD) at Year (Y)1 and Y2, and annualized relapse rate (ARR) at Y2. Changes in intrathecal (OCBs, kappa free light chain [KFLC], immunoglobulin [Ig]G and IgM indices), OCT measures, and neuroaxonal degeneration (neurofilament light chain [NfL]) biomarkers are reported at baseline, month (M)12, and M24. Results: = 17), 76.5% had OCB reduction or disappearance at least once in the study. KFLC and IgG indices were reduced at M24 versus baseline. Sustained reductions were observed in median NfL, while IgG and IgM remained within normal ranges for most participants. Mean OCT measurements showed no retinal nerve fiber thinning. Conclusion: For CladT-treated pwRMS, disease activity and biomarkers of intrathecal inflammation and neuroaxonal damage were reduced versus baseline. Trial registration: ClinicalTrials.gov identifier, NCT03364036. Date registered: June 12, 2017. Date first patient enrolled: May 28, 2018. https://clinicaltrials.gov/study/NCT03364036. Extension study ClinicalTrials.gov Identifier: NCT04783935. Date registered: March 05, 2021. Date first patient enrolled: March 10, 2021. https://clinicaltrials.gov/study/NCT04783935.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".