Titre
Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Gabay, C.
Auteure/Auteur
Fautrel, B.
Auteure/Auteur
Rech, J.
Auteure/Auteur
Spertini, F.
Auteure/Auteur
Feist, E.
Auteure/Auteur
Kötter, I.
Auteure/Auteur
Hachulla, E.
Auteure/Auteur
Morel, J.
Auteure/Auteur
Schaeverbeke, T.
Auteure/Auteur
Hamidou, M.A.
Auteure/Auteur
Martin, T.
Auteure/Auteur
Hellmich, B.
Auteure/Auteur
Lamprecht, P.
Auteure/Auteur
Schulze-Koops, H.
Auteure/Auteur
Courvoisier, D.S.
Auteure/Auteur
Sleight, A.
Auteure/Auteur
Schiffrin, E.J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1468-2060
Statut éditorial
Publié
Date de publication
2018-06
Volume
77
Numéro
6
Première page
840
Dernière page/numéro d’article
847
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.
In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study.
Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria.
Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.
NCT02398435.
In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study.
Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria.
Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.
NCT02398435.
Sujets
PID Serval
serval:BIB_C1D4A65C579D
PMID
Open Access
Oui
Date de création
2018-03-08T16:51:58.437Z
Date de création dans IRIS
2025-05-20T22:45:34Z
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Nom
29472362_BIB_C1D4A65C579D.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc/4.0
Taille
716.09 KB
Format
Adobe PDF
PID Serval
serval:BIB_C1D4A65C579D.P001
URN
urn:nbn:ch:serval-BIB_C1D4A65C579D7
Somme de contrôle
(MD5):e2abbd106b82c633401346845d9a6fc4