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Record W4391165493 · doi:10.1093/ecco-jcc/jjad212.1211

P1081 Pharmacokinetics and immunogenicity of the ustekinumab biosimilar candidate ABP 654 in patients with moderate-to-severe plaque psoriasis

2024· article· en· W4391165493 on OpenAlexaff
Vincent Chow, Daniel T. Mytych, Andrew Blauvelt, Kim Papp, C. Barragán, Paul S. Yamauchi, Jeffrey Crowley, Janet Franklin

Bibliographic record

VenueJournal of Crohn s and Colitis · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicBiosimilars and Bioanalytical Methods
Canadian institutionsProbity Medical Research
Fundersnot available
KeywordsUstekinumabBiosimilarPlaque psoriasisMedicineImmunogenicityPharmacokineticsPsoriasisDermatologyInternal medicinePharmacologyImmunologyAdalimumabImmune systemDisease

Abstract

fetched live from OpenAlex

Abstract Background ABP 654 is being developed as a biosimilar candidate to ustekinumab reference product (RP), a biologic agent used in the treatment of certain chronic, immune-mediated, inflammatory diseases. Previously, we reported no clinically meaningful differences in efficacy or safety between ABP 654 and ustekinumab RP in a 52-week randomised, double-blinded, active-controlled study in patients with moderate-to-severe plaque psoriasis. Here, we describe the pharmacokinetics (PK) and anti-drug antibody (ADA) results from the same study. Methods A total of 563 patients were randomised in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a subcutaneous dose of 45 mg (baseline body weight [BW] ≤ 100 kg) or 90 mg (baseline BW > 100 kg) (Fig. 1). Serum samples for PK and ADA evaluations were collected at various timepoints. Concentrations of ABP 654 and ustekinumab RP were measured using an electrochemiluminescent (ECL) assay based on the Meso Scale Discovery platform. All ADA samples were tested in a validated binding, acid-dissociation ECL assay. Samples testing positive for binding antibodies were evaluated for neutralising ADA in a validated ECL-based affinity capture elution assay. Results From baseline to Week 52, the geometric least-squares (LS) means of trough serum concentrations were similar between the ABP 654 and ustekinumab RP groups. In addition, the geometric LS means of serum concentrations were similar post Week 28 for patients (ABP 654, n=25 and ustekinumab RP, n=34) who received dose intensification. Of patients with a post-baseline ADA result through Week 28, 52 (18.6%) patients in the ABP 654 group and 104 (37.1%) patients in the ustekinumab RP group tested positive for binding ADAs. Of these, 24 (8.6%) patients in the ABP 654 group and 50 (17.9%) patients in the ustekinumab RP group tested positive for neutralising ADAs. For dose intensification patients with a post-baseline result post Week 28, no patients in the ABP 654 group tested positive for binding or neutralising ADAs, and 2 (5.9%) patients in the ustekinumab RP group tested positive for binding and neutralising ADAs. Conclusion Throughout the study, serum trough concentrations remained comparable between ABP 654 and ustekinumab RP. While the percentages of binding and neutralising ADAs were numerically lower for the ABP 654 group compared with the ustekinumab RP group through Week 28 (and in patients who received dose intensification), the available clinical efficacy, safety, and PK data suggest that these differences were not clinically impactful. Overall, the results support a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.586
Threshold uncertainty score0.319

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 head0.009
GPT teacher head0.251
Teacher spread0.243 · 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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Citations2
Published2024
Admission routes1
Has abstractyes

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