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FRI0582 Open-label, multicenter, dose-escalating phase ii clinical trial on the safety and efficacy of tadekinig alpha in adult onset still's disease
  1. C Gabay1,
  2. B Fautrel2,
  3. J Rech3,
  4. F Spertini4,
  5. E Feist5,
  6. I Koetter6,
  7. E Hachulla7,
  8. J Morel8,
  9. T Schaeverbeke9,
  10. MA Hamidou10,
  11. T Martin11,
  12. B Hellmich12,
  13. P Lamprecht13,
  14. H Schultze-Koops14,
  15. A Sleight15,
  16. E Schiffrin15
  1. 1Rheumatology, University Hospitals of Geneva, Geneva, Switzerland
  2. 2Rheumatology, Pitié Salpetrière University Hospital, Paris, France
  3. 3Department of Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany
  4. 4Division of Immunology and Allergy, CHUV, Lausanne, Switzerland
  5. 5Rheumatology, Charité Universitatsmedizin, Berlin
  6. 6Asklepios Klinikum, Hamburg, Germany
  7. 7CHRU de Lille - Hopital Claude Huriez, Lille
  8. 8Department of Rheumatology, University and CHU of Montpellier, Montpellier
  9. 9Rheumatology, Hopital Pellegrin, Bordeaux
  10. 10CHU de Nantes, Nantes
  11. 11University Hospital of Strasbourg, Strasbourg, France
  12. 12Klinik fur Innere Medizin, Rheumatologie und immunologie, Medius Klinik, Kirchheim unter Teck
  13. 13Rheumatology, University of Lübeck, Lübeck
  14. 14Medizinische Klinik und Poliklinik IV, LMU, Muenchen, Germany
  15. 15Ab2 Bio, Lausanne, Switzerland

Abstract

Background Adult Onset Still's Disease (AOSD) is a severe systemic autoinflammatory disease. Elevated interleukin (IL)-18 levels correlate with AOSD disease activity, suggesting a central role

Objectives To examine the safety and efficacy of IL-18 blockade in AOSD with the administration of Tadekinig alpha, a recombinant human IL-18 binding protein

Methods Patients (Pts) with AOSD according to Yamaguchi criteria were included if they had been previously treated for at least one month with corticosteroids (CS). The pts received either 80 mg (group 1) or 160 mg (group 2) Tadekinig alpha sc three times weekly for 12 weeks. Oral CS and/or conventional DMARDs were allowed at stable dose in combination with Tadekinig alpha. After 3 wks, group 1 pts qualified as non responders (CRP levels did not decrease by ≥50% from baseline values or absence of temperature normalization) could be up-dosed to 160 mg for an additional 12 weeks. The primary endpoint was safety and secondary endpoints included early signs of efficacy

Results 23 pts were included (10 and 13 in group 1 and group 2, respectively). 6 pts of group 1 were up-dosed to 160 mg. Baseline characteristics and safety and efficacy results are described in Table 1. Most adverse events (AEs) (47) were considered as mild or moderate. Three serious AEs (SAE) were reported including two that were considered not related to the study drug and one possibly related according to the investigator (toxic optic neuropathy). Four premature discontinuations were related to AEs, including 3 cases of injection site reactions and 1 SAE. Systemic response as defined by ≥70% decrease of serum C-reactive protein (CRP) or normalization of CRP and ferritin levels was obtained in 2/10 and 6/13 pts of groups 1 and 2, respectively in the ITT analysis, and in 2/9 and 6/9 pts of groups 1 and 2, respectively, in the PP analysis.

Table 1.

Baseline characteristics and safety and efficacy results

Conclusions IL-18 blockade by Tadekinig alpha has an acceptable safety profile and is efficacious, in particular at the 160 mg dosage, in patients with refractory AOSD

Disclosure of Interest C. Gabay Grant/research support from: AB2 Bio, Roche, Pfizer, Consultant for: AB2 Bio, Roche, Pfizer, MSD, BMS, AbbVie, Sanofi, B. Fautrel: None declared, J. Rech: None declared, F. Spertini: None declared, E. Feist: None declared, I. Koetter: None declared, E. Hachulla: None declared, J. Morel: None declared, T. Schaeverbeke: None declared, M. Hamidou: None declared, T. Martin: None declared, B. Hellmich: None declared, P. Lamprecht: None declared, H. Schultze-Koops: None declared, A. Sleight Employee of: Ab2 Bio, E. Schiffrin Employee of: Ab2 Bio

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