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.
- Gabay C Department of Internal Medicine Specialties, Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
- Fautrel B UPMC, Pierre Louis Institute of Epidemiology and Public Health, GRC 08, Paris, France.
- Rech J Department of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany.
- Spertini F Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Feist E Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
- Kötter I Department of Internal Medicine/Rheumatology, Nephrology and Immunology, Asklepios Klinikum, Hamburg, Germany.
- Hachulla E Department of Internal Medicine, University of Lille, Lille, France.
- Morel J Department of Rheumatology, University and CHU of Montpellier, Montpellier, France.
- Schaeverbeke T Department of Rheumatology, FHU Acronim, CHU of Bordeaux, Bordeaux, France.
- Hamidou MA Department of Internal Medicine, CHU Nantes, Nantes, France.
- Martin T Department of Clinical Immunology and Internal Medicine, CHU of Strasbourg, Strasbourg, France.
- Hellmich B Department of Internal Medicine, Rheumatology and Immunology, Medius Klinik Kirchheim, Kirchheim unter Teck, Germany.
- Lamprecht P Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
- Schulze-Koops H Department of Internal Medicine IV, Division of Rheumatology and Clinical Immunology, Ludwig-Maximilians-University, Munich, Germany.
- Courvoisier DS Department of Internal Medicine Specialties, Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
- Sleight A AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland.
- Schiffrin EJ AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland.
- 2018-02-24
Published in:
- Annals of the rheumatic diseases. - 2018
adult onset still’s disease
inflammation
juvenile idiopathic arthritis
Adult
Antirheumatic Agents
Biomarkers
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Injections, Subcutaneous
Intercellular Signaling Peptides and Proteins
Interleukin-18
Middle Aged
Severity of Illness Index
Still's Disease, Adult-Onset
Treatment Outcome
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1136/annrheumdis-2017-212608
- PMID 29472362
- Persistent URL
- https://sonar.ch/global/documents/170901
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