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.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_C1D4A65C579D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Annals of the rheumatic diseases
Author(s)
Gabay C., Fautrel B., Rech J., Spertini F., Feist E., Kötter I., Hachulla E., Morel J., Schaeverbeke T., Hamidou M.A., Martin T., Hellmich B., Lamprecht P., Schulze-Koops H., Courvoisier D.S., Sleight A., Schiffrin E.J.
ISSN
1468-2060 (Electronic)
ISSN-L
0003-4967
Publication state
Published
Issued date
06/2018
Peer-reviewed
Oui
Volume
77
Number
6
Pages
840-847
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Adult, Antirheumatic Agents/administration & dosage, Antirheumatic Agents/adverse effects, Antirheumatic Agents/therapeutic use, Biomarkers/blood, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Injections, Subcutaneous, Intercellular Signaling Peptides and Proteins/administration & dosage, Intercellular Signaling Peptides and Proteins/adverse effects, Intercellular Signaling Peptides and Proteins/therapeutic use, Interleukin-18/blood, Middle Aged, Severity of Illness Index, Still's Disease, Adult-Onset/drug therapy, Still's Disease, Adult-Onset/immunology, Treatment Outcome, Young Adult, adult onset still’s disease, inflammation, juvenile idiopathic arthritis
Pubmed
Web of science
Open Access
Yes
Create date
08/03/2018 18:51
Last modification date
20/08/2019 16:36
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