260 Low incidence of both new-onset and flares of uveitis in secukinumab-treated patients with ankylosing spondylitis: clinical trial and post-marketing safety analysis
Notice bibliographique
Résumé
Background: Uveitis, a common extra-articular manifestation of spondyloarthritis, has an estimated prevalence in patients with ankylosing spondylitis (AS) of approximately 33.2%, which increases with disease duration and positive human leukocyte antigen B27 (HLA-B27) status. The exposure-adjusted incidence rate (EAIR) of uveitis (combined new-onset and flares) reported in AS patients treated with tumour necrosis factor inhibitors is 2.6-3.5 per 100 patient-years. Objectives: To assess the incidence of uveitis in secukinumab (SEC)-treated AS patients in long-term pooled clinical data from three Phase 3 trials (MEASURE 1-3 [NCT01358175, NCT01649375, NCT02008916]) and from post-marketing analyses. Methods: Analyses included pooled patient-level data from all patients in MEASURE 1 who received any dose (≥1) of SEC up to the last patient attending week 156 study visit, and up to visit week 156 in MEASURE 2 and visit week 104 in MEASURE 3 for each patient, respectively. Uveitis cases were reported by the principal investigator, and not confirmed by an ophthalmologist. Post-marketing data were from the most recent periodic safety surveillance report. The incidence of uveitis is reported as EAIR per 100 patient-years of SEC exposure. Results: In the Phase 3 AS clinical trials, 135 (17%) patients reported pre-existing (but not active or ongoing) uveitis at baseline (BL) and 589 (74.2%) patients were HLA-B27-positive. The EAIR for uveitis was 1.4 per 100 patient-years over the entire treatment period (n = 794). Among all cases of uveitis (n = 26), 14 (54%) were flares in patients with a history of uveitis at BL (Table 1). The EAIR of uveitis in the post-marketing data (based on cumulative SEC exposure of 96,054 patient-years) was 0.03 per 100 patient-years. Conclusion: In SEC-treated patients with active AS, a low incidence of uveitis was observed, including new-onset cases and flares, in both clinical trials and post-marketing analyses. Safety analysis for uveitis with SEC in AS Data is displayed as n (%), unless otherwise stated; Rates are for uveitis MedDRA preferred term; Data from the PSUR, dated 10th August 2017 - includes all indications; Estimated based on cumulative worldwide sales volume and the average maintenance dose. AS, ankylosing spondylitis; CI, confidence interval; EAIR, exposure-adjusted incidence rate; MedDRA, Medical Dictionary for Regulatory Activities; PSUR, periodic safety update report; SEC, secukinumab. Disclosures: H. Marzo-Ortega: Consultancies; H.M. consulted for: AbbVie, Celgene, Janssen, Novartis and UCB. Member of speakers’ bureau; H. M. participated in speaker bureaus for: AbbVie, Celgene, Janssen and UCB. Grants/research support; H. M. received grant/research support from: Janssen and Pfizer. A. Deodhar: Consultancies; A. D. consulted for: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A. D. received grant/research support from: AbbVie, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. C. Miceli-Richard: Consultancies; C. M. consulted for: Abbott/AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer and Wyeth. Member of speakers’ bureau; C. M. participated in speaker bureaus for: Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough and Wyeth. Grants/research support; C. M. received grant/research support from: Merck, Pfizer, Roche, UCB and Wyeth. X. Baraliakos: Consultancies; X. B. consulted for: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer and UCB. Member of speakers’ bureau; X. B. participated in speaker bureau for: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer and UCB. Grants/research support; X. B. received grant/research support from: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer and UCB. D.D. Gladman: Consultancies; D. G. consulted for: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; D. G. received grant/research support from: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. R. Martin: Shareholder/stock ownership; R. M. is a shareholder at Novartis. Other; R. M. is an employee of Novartis. J. Safi: Shareholder/stock ownership; J. S. is a shareholder and at Novartis. Other; J. S. is an employee of Novartis. B. Porter: Shareholder/stock ownership; B. P. is a shareholder at Novartis. Other; B. P. is an employee of Novartis. A. Shete: Shareholder/stock ownership; A. S. is a shareholder at Novartis. Other; A. S. is an employee of Novartis.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,016 | 0,015 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,004 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».