DOP059 Lack of significance of treatment-emergent anti-drug antibodies on efficacy of mirikizumab in patients with moderately-to-severely active Crohn’s Disease: Results from the VIVID-1 study
Notice bibliographique
Résumé
Abstract Background Results from the phase 3 VIVID-1 study, NCT03926130, showed efficacy of mirikizumab (miri), a p19-directed antibody against IL-23, in patients with moderately-to-severely active Crohn’s disease (CD). VIVID-1 co-primary and gated endpoints, including comparison with ustekinumab (uste), are already reported1, 2. Immunogenicity is recognised as a leading contributor of loss of response to biologic therapies for approved treatments in inflammatory bowel disease3. Patients treated with miri were tested for anti-drug antibodies (ADA) in VIVID-1. We present results showing the immunogenicity effect on miri-treated patients. Methods Patients were randomised 6:3:2 to miri (N=579), uste (N=287), or placebo (N=199) in VIVID-1. Miri was administered intravenously at week (W) 0, W4 and W8 (induction), then subcutaneously every 4 weeks from W12 to W52 (maintenance). A validated acid-dissociation drug resistant assay was developed for the measurement of ADA in multiple patient samples throughout the study. Patients in the primary analysis set who were randomised to miri at baseline and had a non-missing baseline ADA result and at least 1 non-missing postbaseline ADA result were used in the analyses. The potential impact of ADA and ADA titer on efficacy outcomes was assessed using the co-primary efficacy endpoints of VIVID-12. These endpoints were assessed according to the presence or absence of treatment emergent (TE) ADA and by titer groupings. Results were analysed separately for low- and high-titer TE ADA based on a cutoff of 1:160, considering high-titer TE ADA may be more associated with clinical outcomes4. Results Of 571 participants in the analysis population, 12.6% (n=72) were TE ADA-positive. The majority (66.7%, n=48) of TE ADA-positive patients had ADA titers of <1:160. Figure shows that similar proportions of TE ADA-positive and TE ADA-negative patients achieved composite clinical remission and endoscopic improvement after 52 weeks of continuous treatment. Similarly, the subgroup of patients with high-titer TE ADA ≥1:160 achieved comparable rates of composite clinical remission and endoscopic improvement as TE ADA-negative patients. No overall clinically meaningful differences were observed based on TE ADA positivity. Conclusion The results from this study show that the overall immunogenicity of miri is low. TE ADA did not adversely impact the clinical efficacy of miri for patients with moderately-to-severely active CD. This was also true in the subgroup of patients with high-titer TE ADA. References 1.Jairath V, Sands BE, Bossuyt P, et al. OP35 Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn’s disease: Results from the phase 3 VIVID 1 study. J Crohns Colitis 2024;18Supplement_1:i62–i64. 2.Ferrante M, Danese S, Chen M, et al. OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 study. J Crohns Colitis 2024;18Supplement_1:i7-i9. 3.Vermeire S, Gils A, Accossato P, et al. Immunogenicity of biologics in inflammatory bowel disease. Ther Adv Gastroenterol. 2018;11:1–13. 4.Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum. 1997;40(9):1601-11.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,002 | 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 ».