076 Assessment of pain improvement in rheumatoid arthritis patients treated with baricitinib, who were inadequate responders to methotrexate and tumor necrosis factor inhibitors
Notice bibliographique
Résumé
Background: During the development programme, baricitinib (BARI) demonstrated greater and faster pain relief relative to placebo (PBO) and active comparator in different RA populations. Here, we summarise the findings from two recent post hoc analyses focused on the effect of BARI on pain in two clinically relevant patient populations: methotrexate-inadequate responders (MTX-IR; RA-BEAM) and tumor necrosis factor inhibitor-inadequate responders (TNFi-IR; RA-BEACON). Methods: In both clinical trials (RA-BEAM and RA-BEACON), pain was assessed with a visual analog scale (VAS, 0-100 mm) at each study visit. In RA-BEAM, 1,305 patients on stable background MTX were randomized 3:3:2 to PBO, BARI 4-mg, or adalimumab (ADA) 40-mg. The likelihood of achieving ⩾30%, ⩾50%, and ⩾70% pain VAS improvement through Week 24 and the median time when 50% of patients achieved these pain improvement thresholds was assessed with Cox proportional hazard models and the cumulative incidence estimate. Analyses were not adjusted for multiplicity. In RA-BEACON, 527 patients were randomised to placebo (n = 176), BARI 2-mg (n = 174), or 4-mg (n = 177) once daily for 24 weeks. Approximately 40% of patients had received >1 TNF inhibitor and a quarter of patients had received ⩾3 bDMARDs, representing patients with highly refractory disease. The proportion of patients achieving ⩾30%, ⩾50%, and ⩾70% pain relief at Week-12 was compared between BARI 2-mg or 4-mg and PBO using logistic models. Missing pain values were imputed using modified last observation-carried-forward. Results: In the MTX-IR population, BARI-treated patients were more likely to achieve at least 30%, 50%, and 70% pain improvement than PBO and ADA with HR of 1.7, 1.9 and 2.5, respectively (p < 0.001) compared to PBO, and 1.1 (p = 0.145), 1.2 (p = 0.032) and 1.3 (p = 0.003) compared to ADA. The median time for 50% of patients to achieve at least 30%, 50%, and 70% pain improvement, respectively, was 1.9, 4.0 and 12.4 weeks for BARI, 2.0, 7.9 and 20.0 weeks for ADA, and 4.6, 14.0 and >24 weeks for PBO. In the TNFi-IR population, at Week-12, significantly more patients achieved ⩾30%, ⩾50%, and ⩾70% pain relief with BARI 2-mg or 4-mg vs PBO (p < 0.05, for all comparisons). Consistent improvements were observed regardless of baseline pain. Regardless of treatment history, patients receiving BARI 2-mg or 4-mg were more likely to reach all pain relief thresholds than placebo. Conclusion: In both MTX-IR and TNFi-IR populations, BARI demonstrated greater pain improvement than comparators at Weeks 24 and 12, respectively. Disclosures: P.C. Taylor: Grants/research support; Celgene, Eli lilly and company, Galapagos, UBC. Consultant for: AbbVie, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Pfizer, UCB, Biogen, Sandoz, Novartis, Gilead and Janssen. R. Fleischmann: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Celltrion, GSK, Janssen, Eli Lilly and company, Novartis, Pfizer, Samsung, Sanofi-Aventis, tahio. Grants/research support; AbbVie, Amgen, AstraZeneca, Bristol-Myers squibb, Celgene, Centrexion, Genetech, GlaxosmithKline, Janssen, Eli Lilly and company, Merck, Pfizer, Regeneron, Roche, Sanofi, Aventis, UCB. T. Takeuchi: Grants/research support; AbbVie, Asahi Kasei Medical, Astellas Pharma, AstraZeneca, BMS, Chugai Pharma, Daiichi Sankyo, Eisai, Lilly, Janssen, Mitsubishi Tanabe Pharma, Nipponkayaku, Novartis, Pfizer Japan, Takeda, Taiho, Tai. J. Pope: Consultancies; AbbVie, Amgen, Bayer, BMS, Celtrion, Lilly, Merck, Novartis, Pfizer, Roche, UCB. Grants/research support; Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, M.C. Genovese: Grants/research support; Eli Lilly and Company, Abbvie. B. Zhu: Other; Employee of Eli Lilly and Company. C. Gaich: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. X. Zhang: Other; Employee of Eli Lilly and Company. C. Dickson: Other; Employee at Eli Lilly and Company. A. Quebe: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. F. De Leonardis: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. A. Cardoso: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. I. Kouris: Other; Employee of Eli Lilly and Company. P. Durez: Consultancies; Lilly, BMS, Merck, Pfizer, Sanofi, Janssen. Honoraria; Lilly, BMS, Merck, Pfizer, Sanofi, Janssen.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».