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Ann Rheum Dis. 2018 Jun;77(6):840-847. doi: 10.1136/annrheumdis-2017-212608. Epub 2018 Feb 22.

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 information

1
Department of Internal Medicine Specialties, Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
2
UPMC, Pierre Louis Institute of Epidemiology and Public Health, GRC 08, Paris, France.
3
Department of Rheumatology, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
4
Department of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany.
5
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
6
Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
7
Department of Rheumatology and Clinical Immunology, Berlin Institute of Health, Berlin, Germany.
8
Department of Internal Medicine/Rheumatology, Nephrology and Immunology, Asklepios Klinikum, Hamburg, Germany.
9
Department of Internal Medicine, University of Lille, Lille, France.
10
Department of Rheumatology, University and CHU of Montpellier, Montpellier, France.
11
Department of Rheumatology, FHU Acronim, CHU of Bordeaux, Bordeaux, France.
12
Department of Internal Medicine, CHU Nantes, Nantes, France.
13
Faculté de Médecine, Université de Nantes, INSERM UMR 1064, Nantes, France.
14
Department of Clinical Immunology and Internal Medicine, CHU of Strasbourg, Strasbourg, France.
15
Department of Internal Medicine, Rheumatology and Immunology, Medius Klinik Kirchheim, Kirchheim unter Teck, Germany.
16
Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
17
Department of Internal Medicine IV, Division of Rheumatology and Clinical Immunology, Ludwig-Maximilians-University, Munich, Germany.
18
AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland.

Abstract

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.

TRIAL REGISTRATION NUMBER:

NCT02398435.

KEYWORDS:

adult onset still’s disease; inflammation; juvenile idiopathic arthritis

Conflict of interest statement

Competing interests: CG has received grants and personal fees from AB2 Bio Ltd, grants and personal fees from Roche and Pfizer, and personal fees from Merck Sharp & Dohme (MSD), Novartis, Sanofi and AbbVie; BF has received grants from AbbVie, MSD, Pfizer and Roche, and personal fees from AbbVie, Biogen, Bristol-Myers Squibb (BMS), Celgene, Janssen, Lilly, MSD, MEDAC, Nordic, Pfizer, Roche, Swedish Orphan Biovitrum AB (publ) (Sobi), Novartis and Union Chimique Belge (UCB); FS has received grants from AB2 Bio Ltd; EF has received financial and non-financial support from AB2 Bio Ltd; IK has received personal fees from AbbVie, Actelion, BMS, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche and Sobi; TS has received grants and personal fees from Pfizer and Roche, and personal fees from AbbVie, Biogen, BMS, Lilly, MSD, Novartis, Sanofi and UCB; BH has received personal fees from AbbVie, BMS, Novartis, Roche, Pfizer, Celgene and MSD; PL has received non-financial support from AB2 Bio Ltd; DSC has received grants from AB2 Bio Ltd and personal fees from Pfizer, BMS and Janssen; AS and EJS are employees of AB2 Bio Ltd.

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