P135 Efficacy and safety of upadacitinib in TNFi inadequate responders with rheumatoid arthritis from three Phase 3 clinical trials
Notice bibliographique
Résumé
Abstract Background/Aims For patients with RA who are refractory to biologic disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy. In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients. Objectives To describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR). Methods A post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND, -CHOICE, and -COMPARE. For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28-CRP, Clinical Disease Activity Index, and Simple Disease Activity Index, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021. Results 568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; CV risk factors were common among this refractory population. ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND and CHOICE bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups. Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 PY of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND and CHOICE bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events and venous thromboembolism, and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY. Conclusion In this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program. Disclosure R. Fleischmann: Consultancies; Consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer Inc, and UCB. Grants/research support; Grant/research support from AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and. L. Bessette: Consultancies; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. S. Hall: Consultancies; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. J. Sparks: Consultancies; Consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. M. Jain: Consultancies; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. Grants/research support; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. A. Kakehasi: Consultancies; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Member of speakers’ bureau; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Grants/research support; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Y. Song: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. S. Meerwein: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. R. DeMasi: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. J. Suboticki: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. A. Rubbert-Roth: Consultancies; AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur.
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 | 0,011 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,007 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».