263 Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in patients with psoriatic arthritis and ankylosing spondylitis during a 52week treatment period
Notice bibliographique
Résumé
Background: Secukinumab (SEC), a fully human monoclonal antibody (mAb) that selectively targets interleukin-17A, is highly efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). mAb therapies may be associated with immunogenicity (IG) and production of anti-drug antibodies (ADAs) that may cause adverse events (AEs), and affect drug pharmacokinetics (PK) and clinical response. Objectives: To assess the IG of SEC in PsA and AS patients treated with SEC for up to 52 weeks. Methods: IG in patients with PsA (FUTURE 1-3 studies, n = 1414) and AS (MEASURE 1-4 studies, n = 1163) exposed to SEC was evaluated at baseline (BL) and at weeks 12, 16 (AS only), 24 and 52. Treatment emergent (TE)-ADA were defined as a positive ADA signal in ≥ 1 post-treatment sample in patients negative at BL. TE-ADA positive samples were analysed for drug-neutralising potential, SEC impact on PK, IG-related AEs and TE-ADA impact on efficacy through week 52. Results: Of 1414 treated PsA and 1163 treated AS patients with samples for IG evaluation, 5 (0.35%) and 8 (0.68%), respectively, developed TE-ADAs over 52 weeks (Table 1). All but 1 PsA pt were biologic-naive; 2/5 PsA and 1/8 AS patients received concomitant methotrexate, 2/8 AS patients received concomitant sulfasalazine. Associations between TE-ADAs and SEC dose, frequency or mode of administration were not observed. Other than 1 PsA pt, all TE-ADAs were non-neutralising and none were associated with any IG-related AE. All TE-ADAs were associated with normal PK and none were associated with loss of SEC efficacy over 52 weeks. Conclusion: SEC treatment was associated with a low incidence of IG in PsA and AS patients, as shown by TE-ADA detection in only 0.35% PsA patients and 0.68% AS patients over 52 weeks in a database of > 2500 patients, which is consistent with the low incidence of IG (0.4%) seen with SEC in patients with plaque psoriasis. Overview of pts with TE-ADAa Only positive ADA results at the respective study week are shown; Impact on efficacy is defined as: PsA, failure to achieve >20% reduction, compared to BL, in both tender and swollen joint counts; AS, failure to achieve ASAS20, after previously achieving such improvement for at least two consecutive visits prior to the first detection of ADA; Normal PK: concentrations in ADA-positive pts within observed range for all pts without ADA. ADA, anti-drug antibodies; AE, adverse event; AS, ankylosing spondylitis; ASAS, Assessment of Spondyloarthritis International Society; BL, baseline; IG, immunogenicity; Neut-Ab, neutralising antibodies; N, no; PBO, placebo; PK, pharmacokinetics; PsA, psoriatic arthritis; SEC, secukinumab; TE, treatment emergent; Wk, week; Y, yes. Disclosures: I.B. McInnes: Consultancies; I. M. consulted for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. Member of speakers’ bureau; I. M. participated in a speakers’ bureau with: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. Grants/research support; I. M. received grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. A. Deodhar: Consultancies; A. D. consulted for: Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A. D. received grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. D. Gladman: Grants/research support; D. G. received grant/research support from: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. M. Ren: Other; M. R. is an employee of Novartis. S. Spindeldreher: Shareholder/stock ownership; S. S. is a shareholder at Novartis. Other; S. S. is an employee of Novartis. L. Pricop: Shareholder/stock ownership; L. P. is a shareholder at Novartis. Other; L. P. is an employee of Novartis. B. Porter: Shareholder/stock ownership; B. P. is a shareholder at Novartis. Other; B. P. is an employee of Novartis. J. Safi: Shareholder/stock ownership; J. S. is a shareholder at Novartis. Other; J. S. is an employee of Novartis. A. Shete: Shareholder/stock ownership; A. S. is a shareholder at Novartis. Other; A. S. is an employee of Novartis. G. Bruin: Shareholder/stock ownership; G. B. is a shareholder at Novartis. Other; G. B. is an employee of Novartis.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| 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 | 0,000 | 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 ».