O32 Impact of patient baseline characteristics on SLE Responder Index-4 (SRI[4]) responses to deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor in the phase 2 PAISLEY trial in systemic lupus erythematosus
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Résumé
<h3>Objective</h3> Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with moderate to severe plaque psoriasis. Deucravacitinib inhibits TYK2-mediated signaling of cytokines, such as type 1 interferons, involved in systemic lupus erythematosus (SLE). In the 48-week, double-blind, phase 2 PAISLEY trial in patients with active SLE (NCT03252587), all primary and secondary endpoints were met at the 3 mg twice-daily (BID) deucravacitinib dose, including SLE Responder Index-4 (SRI[4]) response rates vs placebo at weeks 32 (primary endpoint) and 48. Week 32 response rates were 34.4% vs 58.2%, 49.5%, and 44.9% with placebo vs deucravacitinib 3 mg BID, 6 mg BID, and 12 mg once daily (QD), respectively. This exploratory analysis assessed the efficacy of deucravacitinib according to patient baseline characteristics. <h3>Methods</h3> In the PAISLEY trial, patients with active SLE were randomized 1:1:1:1 to receive placebo (n=90) or deucravacitinib 3 mg BID (n=91), 6 mg BID (n=93), or 12 mg QD (n=89). SRI(4) response rates at week 32 in the phase 2 PAISLEY trial were evaluated according to select baseline demographics and disease characteristics. Point estimates for response rates with asymptotic CIs were calculated for each treatment arm within each subgroup. All analyses were descriptive. <h3>Results</h3> SRI(4) response rates in most analyzed subgroups were consistent with the observed response rates in the overall population and favored the 3 mg BID deucravacitinib dose. SRI(4) response rates in subgroups defined by race, baseline SLEDAI-2K and glucocorticoid dose, and years since initial diagnosis are provided below (figure 1). Of these, Black/African American race, other race, baseline SLEDAI-2K of <10, baseline glucocorticoid dose of ≥10 mg/day, and 3–6 and ≥6 years since diagnosis showed the greatest difference in SRI(4) responses for those receiving deucravacitinib vs placebo. <h3>Conclusion</h3> Deucravacitinib was associated with improved SRI(4) response rates at week 32 across race, SLEDAI-2K, glucocorticoid dose, and years since diagnosis at baseline subgroups. Data interpretation for some subgroups was limited by low patient numbers. These findings support the efficacy of deucravacitinib in the treatment of patients with active SLE, regardless of patient baseline characteristics. <h3>Acknowledgements</h3> We thank the patients and their families who made this study possible, as well as the clinical teams who participated. This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Angela R. Eder, PhD, of SciMentum, Inc, a Nucleus Group Holdings, Inc, company, and funded by Bristol Myers Squibb. <h3>COI Disclosures</h3> <b>EM:</b> Research support: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, and UCB; Consultancy: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Novartis, and Servier <b>CA:</b> Grant support: AstraZeneca and Bristol Myers Squibb; Advisor or review panel: AstraZeneca, Aurinia, Bristol Myers Squibb, GSK, and Kezar; Speaker/honoraria: AstraZeneca and Aurinia <b>LGP:</b> Consultancy: Aurinia and Bristol Myers Squibb <b>AC:</b> Research support: AstraZeneca and GSK; Consultancy/Speaker: AstraZeneca and GSK; Consultancy: Bristol Myers Squibb, Otsuka, and Roche <b>SP, CH, TW, and SB:</b> Employees and shareholders: Bristol Myers Squibb <b>RK:</b> Employee of Syneos Health, providing statistical services to Bristol Myers Squibb <b>RvV:</b> Research support: Bristol Myers Squibb, GSK, and Eli Lilly; Research support, consultancy, and speaker: UCB; Support for educational programs, consultancy, and speaker: Pfizer; Support for educational programs: Roche; Consultancy and speaker: AbbVie, Galapagos, and Janssen; Consultancy: AstraZeneca, Biogen, Biotest, Celgene, Gilead, and Servier
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,002 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 découle