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Record W2803950719 · doi:10.1136/jnnp-2018-anzan.65

066 Impact of long-term teriflunomide treatment on lymphocyte counts and infections in pooled temso and tower studies

2018· article· en· W2803950719 on OpenAlexaff
Richard Macdonell, Myriam Bénamor, Philippe Truffinet, Karthinathan Thangavelu, Matt Mandel, Mark S. Freedman

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2018
Typearticle
Languageen
FieldMedicine
TopicHematological disorders and diagnostics
Canadian institutionsOttawa HospitalUniversity of Ottawa
Fundersnot available
KeywordsTeriflunomideMedicinePlaceboLymphocyteInternal medicineGastroenterologyPooled analysisAdverse effectImmunologyConfidence intervalMultiple sclerosisPathology

Abstract

fetched live from OpenAlex

Introduction In TEMSO ( NCT00134563 ) and TOWER ( NCT00751881 ), teriflunomide was associated with early reductions in mean lymphocyte counts, which remained within the normal range. Here, we analyse long-term effects of teriflunomide on lymphocyte counts and infections in pooled TEMSO/TOWER core and extension data (TEMSO extension, NCT00803049 ). Methods Pooled data from core studies are reported for patients receiving placebo or teriflunomide 14 mg. In the extensions, placebo-treated patients received active treatment; results from pooled core and extension studies are reported for the teriflunomide 14 mg group. Lymphocyte counts were obtained every 2 weeks until Week 24, and every 6 weeks thereafter. Lymphopenia was identified from 2 consecutive lymphocyte counts below LLN and graded by Common Terminology Criteria for Adverse Events. Results In the core studies, placebo/teriflunomide-treated patients rarely experienced Grade 1 (0.7%/2.1%) or 2 (0.5%/1.4%) lymphopenia. Infections were reported in placebo-treated (40.0%/75.0%) and teriflunomide-treated (73.3%/20.0%) patients with Grade 1 or 2 lymphopenia, respectively. No patients with Grade 1 lymphopenia and 1 placebo-treated patient with Grade 2 lymphopenia developed a serious infection. In the combined core and extension studies, teriflunomide-treated patients (n=1354) experienced few Grade 1 (3.0%) or 2 (2.4%) lymphopenias; infections were reported in 25/40 (62.5%) and 19/33 (57.6%) patients, respectively, vs 718/1281 (56.0%) patients without lymphopenia. Serious infections occurred in patients without lymphopenia (47 patients [3.7%]) and in those with Grade 1 (1 [2.5%]) or Grade 2 (3 [9.1%]) lymphopenia. No Grade 3/4 lymphopenias were recorded. Despite the overall low rate of lymphopenia, occurrence and severity of lymphopenia will also be reported in subgroups of Asian and white patients. Conclusion In long-term TEMSO and TOWER trials, low-grade lymphopenia was uncommon, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia, consistent with an immunomodulatory mechanism of action of teriflunomide with limited impact on protective immunity.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.347

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.030
GPT teacher head0.353
Teacher spread0.323 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2018
Admission routes1
Has abstractyes

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