P277 Ixekizumab shows a distinct pattern of pain improvement beyond measurable inflammation as assessed by MRI, CRP or BASDAI questions 5 and 6 in patients with ankylosing spondylitis
Notice bibliographique
Résumé
Abstract Background/Aims Efficacy of ixekizumab (IXE) in patients (pts) with ankylosing spondylitis (AS) at week (W) 16 in the absence of elevated inflammation as measured by CRP and MRI Spondyloarthritis Research Consortium of Canada (SPARCC) has been previously reported. In this analysis, we evaluated the improvement in pain with IXE based on longitudinal status of objective measures of inflammation by MRI, CRP value, and BASDAI 5/6 over 16W. Methods The Phase III COAST-V (NCT02696785) 52W, multi-center, randomized, double-blind, placebo (PBO)-controlled study examined the efficacy of IXE in pts with active AS. Adalimumab (ADA) was used as an active reference arm for the first 16W. Pts assigned to ADA went through a wash-out period of 6W prior to getting their first dose of IXE. Change in spinal pain at night (SP-N) and Short Form 36 Health Survey Questionnaire (SF-36) Bodily Pain were measured during study visits and analyzed while controlling for inflammation status using MRI, CRP levels and mean of BASDAI 5/6 (Q5: Duration, Q6: Intensity of morning stiffness). Observed data analyses are presented for each group stratified by treatment arm. Initial analysis: ‘controlled inflammation’ is defined as MRI SPARCC SI joint <4 and MRI SPARCC Spine <3 at W16, CRP <5mg/L at every visit W4-16, or BASDAI 5/6 improvement of ≥ 2 points W12 and W16. Second analysis: control is defined as CRP <5 mg/L at every week between W4-16 and MRI SPARCC SI joint <4 at W16 and MRI SPARCC Spine <3 at W16. Results When inflammation is controlled per MRI, pts treated (tx) with IXEQ4W (-3.9 p<0.001) and ADA (-2.8 p=0.02) experienced significant reduction in SP-N vs PBO (-1.6) at W16; further improvements were experienced in pts rerandomized to IXE by W52. When inflammation was not controlled per MRI, IXEQ4W (-3.5 p<0.01) and ADA (-3.1 p=0.02) experienced significant reduction in SP-N at W16; all IXE tx pts had further reductions at W52. When inflammation was controlled per MRI+CRP, IXEQ4W (-3.8 p=0.2) and ADA (-3.1 p=0.4) had reduction in SP-N at W16 vs PBO (-2.4); all IXE groups had further improvements at W52. When inflammation was not controlled as measured by MRI+CRP, IXEQ4W (-3.7 p<0.001) had significant reduction in SP-N vs PBO (-1.7), whereas improvement with ADA (-2.6 p=0.06) was not significant; all IXE tx pts had further reduction by W52. For SF-36 bodily pain, improvements were observed with IXE and ADA at W16 and W52, whether inflammation was controlled or not controlled per MRI, CRP, MRI+CRP, or BASDAI 5/6. Conclusion This analysis adds support to the hypothesis that IXE improves pain in pts with and without measurable inflammation. Disclosure N. Maney: None. K. de Vlam: Consultancies; Celgene, Eli Lilly and Company, Galapagos NV, Novartis, Pfizer, and UCB Pharma. Grants/research support; Celgene. P.G. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma. P.J. Mease: Member of speakers’ bureau; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. P. Rahman: Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. V. Krishnan: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. D. Marcelino Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. S. Park: Shareholder/stock ownership; Eli Lilly and Company. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. W. Maksymowych: Grants/research support; AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Galapagos NV, Janssen, Novartis, Pfizer, and UCB Pharma; and is the Chief Medical Officer of CARE Arthritis Ltd.
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 | 0,001 | 0,001 |
| 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 | 0,001 |
| 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 ».