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Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

2020· article· en· W3096902844 on OpenAlexaff
Roy Fleischmann, Ricardo Blanco, Stephen Hall, G. T. D. Thomson, Filip Van den Bosch, Cristiano A. F. Zerbini, Louis Bessette, J. J. Enejosa, Yihan Li, Yanna Song, Ryan DeMasi, In‐Ho Song

Bibliographic record

VenueAnnals of the Rheumatic Diseases · 2020
Typearticle
Languageen
FieldMedicine
TopicRheumatoid Arthritis Research and Therapies
Canadian institutionsUniversité LavalCentre hospitalier de l'Université LavalResearch Manitoba
FundersRegeneron PharmaceuticalsGenentechCelgeneGilead SciencesAbbVieSanofiAmgenPfizerEli Lilly and CompanyBristol-Myers SquibbGlaxoSmithKline
KeywordsMedicineAdalimumabRheumatoid arthritisAdverse effectInternal medicinePlacebo

Abstract

fetched live from OpenAlex

OBJECTIVES: To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy. METHODS: SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts ('non-responders') and at week 26 based on Clinical Disease Activity Index (CDAI) >10 ('incomplete-responders') without washout. RESULTS: A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups. CONCLUSIONS: These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

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)0.003
metaresearch head score (Gemma)0.002
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.020
GPT teacher head0.270
Teacher spread0.250 · 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".

Quick stats

Citations29
Published2020
Admission routes1
Has abstractyes

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