Lymphocyte Dynamics During and After Fingolimod Therapy: Long-Term Data from the INFORMS Trial (P5.294)
Bibliographic record
Abstract
OBJECTIVE: To evaluate the long-term effect of fingolimod on peripheral lymphocyte counts in patients with multiple sclerosis (MS). BACKGROUND: A reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy. The INFORMS study, conducted in patients with primary progressive MS (PPMS), is the longest controlled trial of fingolimod (≥3 years) to date and provides an opportunity to evaluate the long-term effects of fingolimod on lymphocyte count dynamics. METHODS: INFORMS was an international, double-blind trial that randomized patients to fingolimod 0.5 mg (n=336) or placebo (n=487). Inclusion criteria included: a PPMS clinical diagnosis; disease duration 2-10 years; and objective evidence of disability progression within 2 years. Lymphocyte counts were measured at each study visit. Study drug was interrupted for patients with confirmed on-study lymphocyte counts <0.2X109/L. RESULTS: Within 1 month of fingolimod 0.5mg initiation, mean (SD) lymphocyte counts were reduced to 29[percnt] of baseline values (baseline: 1.79X109/L [0.54]; Month 1: 0.52X109/L [0.28]; n=318). Mean counts remained stable with fingolimod 0.5 mg at 26-29[percnt] of baseline values for all time-points up to 4 years (Month 48: 0.49X109/L [0.28]; n=59). Following fingolimod discontinuation, mean lymphocyte counts returned to 76[percnt] of baseline values at 3 months (1.39X109/L [0.62]; n=74) and 86[percnt] at 6 months (1.70X109/L [0.59]; n=35). Placebo-treated patients experienced no marked change in mean lymphocyte counts with values of 96-102[percnt] of baseline levels up to 4 years. The incidence of infection and infestation was comparable between the fingolimod 0.5mg and placebo groups, in line with previous studies in relapsing MS. CONCLUSIONS: Fingolimod induced a rapid reduction in lymphocyte counts that subsequently remained stable and did not increase the overall incidence of infections and infestations relative to placebo for up to 5 years treatment. Lymphocyte counts returned towards normal within 3-6 months of fingolimod discontinuation. Study Supported by Novartis Pharma AG
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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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".