Title :

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.

Author(s) :

Gabay, Cem [Auteur]
Fautrel, Bruno [Auteur]
Université Pierre et Marie Curie - Paris 6 [UPMC]
Rech, Jurgen [Auteur]
Spertini, Francois [Auteur]
Feist, Eugen [Auteur]
Kotter, Ina [Auteur]
Hachulla, Eric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Morel, Jacques [Auteur]
Schaeverbeke, Thierry [Auteur]
Hamidou, Mohamed [Auteur]
Université de Nantes [UN]
Martin, Thierry [Auteur]
Laboratoire de Génie des Procédés et Matériaux - EA 4038 [LGPM]
Hellmich, Bernhard [Auteur]
Lamprecht, Peter [Auteur]
Schulze-Koops, Hendrik [Auteur]
Courvoisier Delphine, Sophie [Auteur]
Sleight, Andrew [Auteur]
Schiffrin Eduardo, Jorge [Auteur]

Journal title :

Annals of the Rheumatic Diseases

Abbreviated title :

Ann. Rheum. Dis.

Volume number :

77

Pages :

840-847

Publication date :

2018-05-10

ISSN :

1468-2060

Keyword(s) :

adult onset still''s disease
inflammation
juvenile idiopathic arthritis

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Objectives : 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 ...
Show more >Objectives : 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. Methods : 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. Results : 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. Conclusions : 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Immunity, inflammation and fibrsis in auto and allo-reactivity

Submission date :

2019-03-01T14:46:26Z
2024-01-25T09:39:26Z