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Canakinumab for Treatment of Adult-Onset Still’s Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial
  1. Claudia Kedor1,
  2. Joachim Listing2,
  3. Jan Zernicke1,
  4. Anja Weiß2,
  5. Frank Behrens3,
  6. Norbert Blank4,
  7. Joerg Christoph Henes5,
  8. Joern Kekow6,
  9. Andrea Rubbert-Roth7,
  10. Hendrik Schulze-Koops8,
  11. Eva Seipelt9,
  12. Christof Specker10,
  13. Eugen Feist1
  1. 1 Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
  2. 2 Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany
  3. 3 CIRI/Rheumatology and Fraunhofer TMP, Goethe-University, Frankfurt, Germany
  4. 4 Internal Medicine 5, University of Heidelberg, Heidelberg, Germany
  5. 5 Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmology), University Hospital Tuebingen, Tuebingen, Germany
  6. 6 Clinic of Rheumatology and Orthopaedics, Otto-von-Guericke University Magdeburg, Vogelsang-Gommern, Germany
  7. 7 Division of Rheumatology, Cantonal Hospital St Gallen, St Gallen, Switzerland
  8. 8 Department of Rheumatology, University of Munich, Munich, Germany
  9. 9 Abteilung Rheumatologie und Klinische Immunologie, Immanuel Krankenhaus Berlin, Standort Berlin-Buch, Berlin, Germany
  10. 10 Klinik für Rheumatologie und Klinische Immunologie, KEM Kliniken Essen-Mitte, Essen, Germany
  1. Correspondence to Claudia Kedor, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin 10117, Germany; claudia.kedor{at}charite.de

Abstract

Background Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).

Objective To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.

Methods Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).

Results At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.

Conclusion Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

  • adult onset still's disease
  • arthritis
  • disease activity
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors CK did literature research, designed the study, recruited patients, collected data, advised on data analysis, interpreted the data, and wrote and revised the report. JL advised on study design, planned the randomisation, and analysed and interpreted the data. JZ designed the study, recruited patients, collected data and revised the report. AW performed the randomisation and revised the report. FB recruited patients, collected data, advised on data analysis, advised interpreting data, and revised the report. NB recruited patients, collected data, advised on data analysis, advised interpreting data and revised the report. JCH recruited patients, collected data, advised on data analysis, advised on interpreting data and revised the report. JK recruited patients, collected data, advised on data analysis, advised on interpreting data and revised the report. AR-R recruited patients, collected data and revised the report. HS-K recruited patients, collected data, advised on data analysis, advised on interpreting data and revised the report. ES recruited patients, collected data and revised the report. CS recruited patients, collected data, advised on data analysis, advised on interpreting data and revised the report. EF did literature research, designed the study, recruited patients, collected data, advised on data analysis, interpreted the data, and wrote and revised the report.

  • Funding This was an investigator-initiated trial sponsored by Novartis Pharma GmbH.

  • Competing interests CK has received personal advisory board and congress fees from Novartis, Pfizer, Roche and Sobi. FB has received grants from Abbvie, Pfizer, Roche, Chugai and Janssen, and consultant, speaker or advisory board fees from Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme and Lilly; Boehringer; and Sandoz. NB has received grants from Novartis and Sobi, and personal fees from Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim and Roche. JCH has received grants from Novartis, Roche and Celgene, and advisory board and speaker fees from Novartis, Roche, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim and Celgene. AR-R has received speaker fees from UCB, and advisory board and speaker fees from Novartis, Roche, Lilly, Pfizer, Abbvie, BMS, Janssen, Sanofi and Celgene. CS has received personal fees from Abbvie, Boehringer-Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB and Toshiba. EF has received advisory board and speaker fees from Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD and Sanofi.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was conducted according to the ethical principles of the Declaration of Helsinki. The study protocol and all amendments were reviewed by the Independent Ethics Commission of the State of Berlin (Ethik-Kommission des Landes Berlin) and independent ethics committees for each centre (EudraCT number 2011-001027-20, protocol number CACZ885GDE01T, ethics number 11/0561–ZS EK 11).

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

  • Data availability statement All data relevant to the study are included in the manuscript or available in supplemental

    material. Complete data and raw data/datasets are saved in the Institution Server and are available upon request.

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