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217. Long-Term (104-Week) Efficacy and Safety Profile of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results from a Phase III, Randomized, Controlled Trial and Open-Label Extension (PALACE 1)

2015· article· en· W2278042283 on OpenAlexaff
Adewale Adebajo, Dafna D. Gladman, Arthur Kavanaugh, Philip J. Mease, Juan J. Gómez‐Reino, Stephen Hall, Éric Lespessailles, Georg Schett, K. Shah, ChiaChi Hu, J. Wollenhaupt

Bibliographic record

VenueLara D. Veeken · 2015
Typearticle
Languageen
FieldMedicine
TopicPharmaceutical studies and practices
Canadian institutionsToronto Western Hospital
Fundersnot available
KeywordsApremilastMedicineOpen labelPsoriatic arthritisRandomized controlled trialInternal medicineDermatologyArthritisPharmacology

Abstract

fetched live from OpenAlex

Background: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, helps regulate immune responses in PsA. PALACE 1 compared the efficacy/safety of APR with placebo in patients with active PsA despite prior conventional DMARDs and/or biologics. We report the efficacy/safety of APR treatment over 104 weeks. Methods: Patients were randomized (1:1:1) to placebo, APR 20 mg b.i.d. (APR20), or APR 30 mg b.i.d. (APR30) stratified by baseline DMARD use (yes/no). Patients whose swollen/tender joint counts (SJC/TJC) had not improved ≥20% at week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if initially randomized to placebo, or continued on their initial APR dose. At week 24, all remaining placebo patients were re-randomized (1:1) to APR20 or APR30. Double-blind APR treatment continued to week 52; patients could continue APR up to 4 additional years. Results: 504 randomized patients received ≥1 dose of study medication (placebo n = 168; APR20 n = 168; APR30 n = 168). At week 52, modified ACR20 response was achieved by 63.0% and 54.6% of patients continually treated with APR20 or APR30 from baseline, respectively. Approximately 80% (285/344) of randomized patients completing Week 52 were still receiving APR at the data cutoff during their second year of APR exposure. Patients receiving APR from baseline demonstrated sustained improvements at Week 104 in modified ACR20/ACR50/ACR70 response [61.3%/29.8%/16.0% (APR20) and 66.3%/35.6%/19.8% (APR30)]; median percentage change in SJC/TJC [−88.9%/−80.5% (APR20) and −87.5%/−76.7% (APR30)]; mean change in HAQ-DI [−0.33 (APR20) and −0.43 (APR30)]; mean change in DAS28 [CRP; −1.61 mg/l (APR20) and −1.83 mg/l (APR30)]; achievement of DAS28 (CRP) <2.6 mg/l [35.1% (APR20) and 38.6% (APR30)]; and PASI-50/PASI-75 response [53.7%/36.6% (APR20) and 54.7%/30.2% (APR30)]. No new safety concerns were observed with treatment through week 104. During weeks >52 to ≤104, adverse events (AEs) occurring in ≥5% of APR-exposed patients were nasopharyngitis and upper respiratory tract infection; most AEs were mild/moderate in severity with no long-term increase in AE incidence and severity. Diarrhoea and nausea occurred at lower rates in weeks >52 to ≤104 (1.7% and 1.2%, respectively) than in weeks 0 to ≤52 (15.3% and 12.4%, respectively). Serious AEs occurred in 6.4% (APR20) and 4.7% (APR30) over weeks >52 to ≤104. Fewer discontinuations due to AEs occurred during weeks >52 to ≤104 (1.5%) than weeks 0 to ≤52 (8.2%).

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)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.021
Threshold uncertainty score0.830

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
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 head0.055
GPT teacher head0.353
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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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

Citations13
Published2015
Admission routes1
Has abstractyes

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