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Clinical and epidemiological research
Extended report
Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study
  1. Marco Gattorno1,
  2. Laura Obici2,
  3. Marco Cattalini3,
  4. Vincent Tormey4,
  5. Ken Abrams5,
  6. Nicole Davis5,
  7. Antonio Speziale6,
  8. Suraj G Bhansali5,
  9. Alberto Martini1,7,
  10. Helen J Lachmann8
  1. 1UO Pediatria 2, Reumatologia, Eurofever project, G Gaslini Institute, Genoa, Italy
  2. 2Amyloidosis Research and Treatment Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  3. 3Pediatric Clinic, University of Brescia and Spedali Civili, Brescia, Italy
  4. 4Galway University Hospitals, Galway, Ireland
  5. 5Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA
  6. 6Novartis Pharma AG, Basel, Switzerland
  7. 7Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal-Fetal Medicine (DINOGMI), University of Genoa, Genoa, Italy
  8. 8Division of Medicine, National Amyloidosis Center, University College London Medical School, London, UK
  1. Correspondence to Dr Marco Gattorno, UO Pediatria 2, Istituto G. Gaslini, Via G. Gaslini 5, Genova 16147, Italy; marcogattorno{at}ospedale-gaslini.ge.it

Abstract

Objective To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1β antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor-associated periodic syndrome (TRAPS).

Methods Twenty patients (aged 7–78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those ≤40 kg) in this open-label, proof-of-concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score ≤1) and full or partial serological remission.

Results Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data.

Conclusions Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment.

Trial registration number NCT01242813; Results.

  • Cytokines
  • Fever Syndromes
  • TNF-alpha
  • Treatment

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-2015-209031

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    Footnotes

    • Handling editor Tore K Kvien

    • Funding This study was sponsored and funded by Novartis.

    • Competing interests KA: employee of Novartis Pharmaceuticals Corporation. SB: employee of Novartis Pharmaceuticals Corporation. MC: received speaker fees and served as a consultant for Novartis and SOBI. ND: employee of Novartis Pharmaceuticals Corporation. MG: received speaker fees and served as a consultant for Novartis and SOBI, and has received unrestricted grants for the Eurofever Registry from Novartis and SOBI. HL: received speaker fees and served as a consultant for Novartis and SOBI. AM: received speaker fees and served as a consultant for Novartis. LO: received speaker fees and served as a consultant for Novartis. AS: employee of Novartis Pharma AG.

    • 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 committee (IEC) or institutional review board (IRB) for each centre: Clinical Research Ethics Committee, Merlin Park Hospital, Galway, Ireland; National Research Ethics Service, Southampton & South West Hampshire REC(B), Berkshire, UK; Comitato Di Bioetica Dell’ IRCCS Istituto Giannina Gaslini Di Genova, Genova, Italy; Comitato Di Bioetica Della Fondazione IRCCS Policlinico San Matteo Di Pavia, Pavia, Italy; Comitato Etico Azienda ospedaliera Spedali Civili Di Brescia, Brescia, Italy; Comitato Etico Dell'ASL 1 Di Agrigento, Agrigento, Italy.

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

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