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
| Autor: | Peter Lamprecht, Thierry Schaeverbeke, Hendrik Schulze-Koops, Eugen Feist, Jürgen Rech, Bernhard Hellmich, Eduardo Schiffrin, Delphine S. Courvoisier, Jacques Morel, Thierry Martin, Eric Hachulla, Bruno Fautrel, Andrew Sleight, Cem Gabay, Ina Kötter, Mohamed Hamidou, François Spertini |
|---|---|
| Přispěvatelé: | Department of Pathology and Immunology [Geneva, Switzerland] (Clinical Pathology Division), University of Geneva [Switzerland]-Geneva University Hospitals - HUG [Switzerland], Division of Rheumatology [Geneva, Switzerland], Geneva University Hospital, Geneva-Department of Internal Medicine [Genève], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Division of Immunology and Allergy [Lausanne, Suisse], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Department of Internal Medicine II, University of Tübingen, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Degauque, Nicolas, Université de Genève = University of Geneva (UNIGE)-Geneva University Hospitals - HUG [Switzerland], Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen |
| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty [SDV.IMM] Life Sciences [q-bio]/Immunology Injections Subcutaneous Immunology Disease Severity of Illness Index Drug Administration Schedule General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences 0302 clinical medicine Team4 Rheumatology Prednisone Internal medicine medicine Clinical endpoint Humans Immunology and Allergy CRTI Adverse effect ComputingMilieux_MISCELLANEOUS ddc:616 030203 arthritis & rheumatology Dose-Response Relationship Drug biology business.industry C-reactive protein Interleukin-18 Interleukin Middle Aged Antirheumatic Agents/administration & dosage Antirheumatic Agents/adverse effects Antirheumatic Agents/therapeutic use Biomarkers/blood Female Intercellular Signaling Peptides and Proteins/administration & dosage Intercellular Signaling Peptides and Proteins/adverse effects Intercellular Signaling Peptides and Proteins/therapeutic use Interleukin-18/blood Still's Disease Adult-Onset/drug therapy Still's Disease Adult-Onset/immunology Treatment Outcome adult onset still’s disease inflammation juvenile idiopathic arthritis 3. Good health Clinical trial Institutional repository 030104 developmental biology Antirheumatic Agents biology.protein Intercellular Signaling Peptides and Proteins [SDV.IMM]Life Sciences [q-bio]/Immunology business Still's Disease Adult-Onset Biomarkers medicine.drug |
| Zdroj: | Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases, BMJ Publishing Group, 2018, 13, pp.annrheumdis--2017--212608. ⟨10.1136/annrheumdis-2017-212608⟩ Annals of the Rheumatic Diseases, Vol. 77, No 6 (2018) pp. 840-847 Annals of the Rheumatic Diseases, 2018, 13, pp.annrheumdis--2017--212608. ⟨10.1136/annrheumdis-2017-212608⟩ Annals of the rheumatic diseases, vol. 77, no. 6, pp. 840-847 |
| ISSN: | 1468-2060 0003-4967 0239-8435 |
| DOI: | 10.1136/annrheumdis-2017-212608 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|