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S760 Persistence of Tofacitinib Treatment in Patients With Ulcerative Colitis Who Entered the Open-Label, Long-Term Extension Study, OCTAVE OPEN in Remission or With a Clinical Response

2021· article· en· W4213158448 on OpenAlexaff
Remo Panaccione, María T. Abreu, Irina Lazariciu, Rajiv Mundayat, Nervin Lawendy, Leonardo Salese, John Woolcott, Bruce E. Sands, María Chaparro

Bibliographic record

VenueThe American Journal of Gastroenterology · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsTofacitinibMedicineDiscontinuationTolerabilityInternal medicineOpen labelJanus kinase inhibitorUlcerative colitisOctave (electronics)GastroenterologyClinical trialAdverse effectDiseaseRheumatoid arthritis

Abstract

fetched live from OpenAlex

Introduction: Drug survival in open-label, long-term extension (OLE) studies may provide important information on the long-term efficacy and tolerability of a therapy. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Efficacy and safety were demonstrated in three Phase 3, randomized, PBO-controlled studies in patients (pts) with moderate to severe UC. A Phase 3, OLE study (OCTAVE Open, NCT01470612) included pts from OCTAVE Induction 1 & 2 and OCTAVE Sustain. Methods: Data on the persistence of tofacitinib treatment in the OLE study for pts who had a clinical response at Week (Wk) 52 of treatment with tofacitinib 5 or 10 mg BID, or PBO, in OCTAVE Sustain were evaluated. Data were analyzed for all responder pts and by remission status: responders who were also in remission (remitters; assigned to tofacitinib 5 mg BID per OLE study protocol), and responders who were not in remission (responders/non-remitters) at OLE baseline (assigned to tofacitinib 10 mg BID per OLE study protocol) (Figure 1). Duration of treatment in the OLE study varied by pt. Results: At baseline of the OLE study, there were 280 pts with a clinical response (all responders) which included 164 remitters and 116 responders/non-remitters who were treated for a maximum of 7 years in the OLE study (Table 1). Of these, 118 (42.1%) pts discontinued the OLE study (68/164 [41.5%] among remitters and 50/116 [43.1%] among responders/non-remitters) with a median time to discontinuation of 291 wks. Overall, the estimated 2- and 5-year tofacitinib persistence rates in the all-responder population were 73.9% and 54.5%, respectively. These rates were numerically higher in remitters (76.8% and 56.9%, respectively) vs responders/non-remitters (69.8% and 50.0%, respectively). During the OLE study, 43 (26.2%) remitters increased tofacitinib dose from 5 to 10 mg BID, and 15 (12.9%) responders/non-remitters decreased tofacitinib dose from 10 to 5 mg BID. Conclusion: With up to 7 years of follow-up, treatment persistence to tofacitinib was highest amongst pts who were responders/remitters compared with responders/non-remitters and the majority of pts continued to be on treatment at 5 years. Analyses are post hoc and limited by sample size. Further research will help to understand the reasons for continuation or discontinuation of tofacitinib treatment in pts with UC.Figure 1.: Mean change from baseline in A) abdominal pain and B) stool frequency through Week 12.Table 1.: Pregnancy outcomes following maternal exposure to CZP. [a] All CZP-exposed pregnancies in women with CID, including those with CD; [b] Multiple births are counted as separate outcomes, so the total number of outcomes is higher than the total number of patients/pregnancies; [c] Reported using the total number of patients/pregnancies as the denominator; [d] Delivery before 37 weeks’ gestation. CD: Crohn’s disease; CID: chronic inflammatory disease; CZP: certolizumab pegol; SD: standard deviation.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.038
GPT teacher head0.336
Teacher spread0.298 · 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 source (direct Gemma or distilled Codex), 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
Published2021
Admission routes1
Has abstractyes

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