E064 The relationship between lipid profile changes and inflammation across the Phase 3 sarilumab rheumatoid arthritis (RA) development programme
Notice bibliographique
Résumé
Background: Serum lipids may be reduced in the setting of chronic inflammation associated with active RA, and they may increase following an effective response to RA therapy, which may be associated with decreased cardiovascular risk, an effect known as the lipid paradox. Sarilumab, an IL-6R blocker approved for the treatment of RA, showed superiority to placebo and adalimumab in RA Phase 3 trials. In this post hoc analysis, we investigated the relationship between lipid levels and markers of inflammation in these trials. Methods: Fasting total (TC), high- (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides, lipoprotein (a) (Lp(a)), and apolipoproteins (Apo) A and B were evaluated in two placebo-controlled studies of sarilumab (150 mg and 200 mg q2w) +csDMARDs in patients with inadequate response (IR) to methotrexate (MOBILITY; NCT01061736) or IR/intolerance to tumour necrosis factor inhibitors (TARGET; NCT01709578) and in a monotherapy study of sarilumab vs adalimumab (MONARCH; NCT02332590). Spearman and Pearson correlations compared relationships between lipid levels and inflammatory markers (C-reactive protein [CRP] and serum amyloid A [SAA, MOBILITY only]). Results: Safety profile of sarilumab has been previously reported; there was no increased risk of major adverse cardiac events with sarilumab. In 52-week MOBILITY and 24-week TARGET, both sarilumab doses led to increases in TC, HDL-C, LDL-C, and triglyceride levels vs placebo (as early as Week 2), and these increases were maintained. In MONARCH, compared to adalimumab, sarilumab treatment led to a greater increase from baseline in TC (16.3 vs 1.4 mg/dL), HDL-C (1.4 vs -0.2), LDL-C (10.5 vs 0.5), and triglycerides (26.6 vs 5.7) and a greater decrease in Lp(a) (-41% vs -2.8%). Changes from baseline in TC/HDL-C ratio for sarilumab 200 mg vs placebo were 0.41 vs 0.01 (MOBILITY Week 52), 0.32 vs -0.06 (TARGET Week 24) and for sarilumab vs adalimumab were 0.22 vs 0.02 (MONARCH Week 24). Sarilumab reduced CRP and SAA (MOBILITY) vs placebo and adalimumab. Negative Spearman correlations (nominal P < 0.001 or P < 0.0001) between decreases from baseline in CRP and increases in lipid levels were seen with adalimumab (data not shown) and with sarilumab 200 mg for TC (-0.26 [MOBILITY Week 52] and -0.33 [TARGET Week 24]), HDL-C (-0.26 TARGET Week 24), LDL-C (-0.21 [MOBILITY Week 24] and -0.25 [TARGET Week 24]), and triglycerides (-0.21 [MOBILITY Week 52]). Conclusion: Sarilumab treatment resulted in increases in lipid parameters vs placebo or adalimumab and reductions in Lp(a). This was seen relatively quickly and stabilised after 4 weeks. Lipid elevation was associated with a reduction in inflammatory markers and was consistent with IL-6 blockade. Disclosures: C. Charles-Schoeman: Consultancies; Regeneron-Sanofi, Pfizer, Octapharma, Amgen, and Gilead. Grants/research support; Bristol-Myers Squibb, AbbVie, Octapharma, and Pfizer. G. St John: Corporate appointments; Regeneron Pharmaceuticals, Inc. Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. H. Leher: Corporate appointments; Regeneron Pharmaceuticals, Inc. Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. T. Kimura: Corporate appointments; Regeneron Pharmaceuticals, Inc. Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. H. van Hoogstraten: Corporate appointments; Sanofi Genzyme. Shareholder/stock ownership; Sanofi Genzyme. M. Nurmohamed: Honoraria; AbbVie, Pfizer, Merck, Roche, BMS, UCB, Sanofi, Eli Lilly, Celgene, and Janssen. Grants/research support; AbbVie, Pfizer, Merck, Roche, BMS, UCB, Sanofi, Eli Lilly, Celgene, and Janssen. M.A. González-Gay: Consultancies; AbbVie, Roche, Sanofi, Eli Lilly, and Novartis. Grants/research support; AbbVie, Roche, Sanofi, Eli Lilly, and Novartis. E. Wilson: Corporate appointments; Sanofi Genzyme. Shareholder/stock ownership; Sanofi Genzyme. E.C. Keystone: Consultancies; AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, P. Honoraria; Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, and Sanofi-Aventis.
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 | 0,008 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,016 | 0,002 |
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 ».