Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study.
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 Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months.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 All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days).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.


BACKGROUND
NCT01242813; Results.
UO Pediatria 2, Reumatologia, Eurofever project, G Gaslini Institute, Genoa, Italy.
Marco
M
Gattorno
Amyloidosis Research and Treatment Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Laura
L
Obici
Pediatric Clinic, University of Brescia and Spedali Civili, Brescia, Italy.
Marco
M
Cattalini
Galway University Hospitals, Galway, Ireland.
Vincent
V
Tormey
Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.
Ken
K
Abrams
Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.
Nicole
N
Davis
Novartis Pharma AG, Basel, Switzerland.
Antonio
A
Speziale
Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.
Suraj G
SG
Bhansali
UO Pediatria 2, Reumatologia, Eurofever project, G Gaslini Institute, Genoa, Italy.|Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal-Fetal Medicine (DINOGMI), University of Genoa, Genoa, Italy.
Alberto
A
Martini
Division of Medicine, National Amyloidosis Center, University College London Medical School, London, UK.
Helen J
HJ
Lachmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002908:Chronic Disease; D004334:Drug Administration Schedule; D010505:Familial Mediterranean Fever / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; C541220:canakinumab
Cytokines; Fever Syndromes; TNF-alpha; Treatment