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  • 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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Clinical and epidemiological research
Extended report
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
  1. Cem Gabay1,
  2. Bruno Fautrel2,3,
  3. Jürgen Rech4,
  4. François Spertini5,
  5. Eugen Feist6,7,
  6. Ina Kötter8,
  7. Eric Hachulla9,
  8. Jacques Morel10,
  9. Thierry Schaeverbeke11,
  10. Mohamed A Hamidou12,13,
  11. Thierry Martin14,
  12. Bernhard Hellmich15,
  13. Peter Lamprecht16,
  14. Hendrik Schulze-Koops17,
  15. Delphine Sophie Courvoisier1,
  16. Andrew Sleight18,
  17. Eduardo Jorge Schiffrin18
  1. 1 Department of Internal Medicine Specialties, Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland
  2. 2 UPMC, Pierre Louis Institute of Epidemiology and Public Health, GRC 08, Paris, France
  3. 3 Department of Rheumatology, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France
  4. 4 Department of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany
  5. 5 Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  6. 6 Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
  7. 7 Department of Rheumatology and Clinical Immunology, Berlin Institute of Health, Berlin, Germany
  8. 8 Department of Internal Medicine/Rheumatology, Nephrology and Immunology, Asklepios Klinikum, Hamburg, Germany
  9. 9 Department of Internal Medicine, University of Lille, Lille, France
  10. 10 Department of Rheumatology, University and CHU of Montpellier, Montpellier, France
  11. 11 Department of Rheumatology, FHU Acronim, CHU of Bordeaux, Bordeaux, France
  12. 12 Department of Internal Medicine, CHU Nantes, Nantes, France
  13. 13 Faculté de Médecine, Université de Nantes, INSERM UMR 1064, Nantes, France
  14. 14 Department of Clinical Immunology and Internal Medicine, CHU of Strasbourg, Strasbourg, France
  15. 15 Department of Internal Medicine, Rheumatology and Immunology, Medius Klinik Kirchheim, Kirchheim unter Teck, Germany
  16. 16 Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
  17. 17 Department of Internal Medicine IV, Division of Rheumatology and Clinical Immunology, Ludwig-Maximilians-University, Munich, Germany
  18. 18 AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland
  1. Correspondence to Professor Cem Gabay, Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva 1205, Switzerland; cem.gabay{at}hcuge.ch

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.

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

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2017-212608

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors CG, BF, JR, JM, AS and EJS contributed to the conception and design of this study. CG, BF, JR, FS, EF, IK, EH, JM, TS, MAH, TM, BH, PL and HSK recruited patients into the study and participated in data collection. CG, FS, EH, DSC, AS and EJS contributed to the data analysis. All authors contributed to data interpretation, critically reviewed the article for important intellectual content and approved the final draft for submission.

    • Funding This study was sponsored by AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland.

    • 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.

    • Ethics approval The study was approved by each centre’s institutional review board or ethics committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Further data on SF12 can be shared upon request to the sponsor of the study.

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