Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results)

Tomoyuki Imagawa, Ryuta Nishikomori, Hidetoshi Takada, Saoko Takeshita, Neha Patel, Dennis Kim, Karine Lheritier, Toshio Heike, Toshiro Hara, Shumpei Yokota

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS. Methods In this open-label study, 19 Japanese CAPS patients aged =2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight = 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24. Results A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study. Conclusion Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.

Original languageEnglish
Pages (from-to)302-309
Number of pages8
JournalClinical and Experimental Rheumatology
Volume31
Issue number2
Publication statusPublished - 2013

Fingerprint

Cryopyrin-Associated Periodic Syndromes
Phenotype
Safety
Interleukin-1
canakinumab
Aseptic Meningitis
Recurrence
Optic Neuritis
Sensorineural Hearing Loss
Exanthema
Fever

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results). / Imagawa, Tomoyuki; Nishikomori, Ryuta; Takada, Hidetoshi; Takeshita, Saoko; Patel, Neha; Kim, Dennis; Lheritier, Karine; Heike, Toshio; Hara, Toshiro; Yokota, Shumpei.

In: Clinical and Experimental Rheumatology, Vol. 31, No. 2, 2013, p. 302-309.

Research output: Contribution to journalArticle

Imagawa, T, Nishikomori, R, Takada, H, Takeshita, S, Patel, N, Kim, D, Lheritier, K, Heike, T, Hara, T & Yokota, S 2013, 'Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results)', Clinical and Experimental Rheumatology, vol. 31, no. 2, pp. 302-309.
Imagawa, Tomoyuki ; Nishikomori, Ryuta ; Takada, Hidetoshi ; Takeshita, Saoko ; Patel, Neha ; Kim, Dennis ; Lheritier, Karine ; Heike, Toshio ; Hara, Toshiro ; Yokota, Shumpei. / Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results). In: Clinical and Experimental Rheumatology. 2013 ; Vol. 31, No. 2. pp. 302-309.
@article{1f878719c9e74d469d78c9face300008,
title = "Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results)",
abstract = "Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS. Methods In this open-label study, 19 Japanese CAPS patients aged =2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight = 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24. Results A complete response was achieved in 18 (94.7{\%}) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8{\%}) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5{\%} at baseline versus 31.6{\%} at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study. Conclusion Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.",
author = "Tomoyuki Imagawa and Ryuta Nishikomori and Hidetoshi Takada and Saoko Takeshita and Neha Patel and Dennis Kim and Karine Lheritier and Toshio Heike and Toshiro Hara and Shumpei Yokota",
year = "2013",
language = "English",
volume = "31",
pages = "302--309",
journal = "Clinical and Experimental Rheumatology",
issn = "0392-856X",
publisher = "Clinical and Experimental Rheumatology S.A.S.",
number = "2",

}

TY - JOUR

T1 - Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first open-label, phase-3 pivotal study (24-week results)

AU - Imagawa, Tomoyuki

AU - Nishikomori, Ryuta

AU - Takada, Hidetoshi

AU - Takeshita, Saoko

AU - Patel, Neha

AU - Kim, Dennis

AU - Lheritier, Karine

AU - Heike, Toshio

AU - Hara, Toshiro

AU - Yokota, Shumpei

PY - 2013

Y1 - 2013

N2 - Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS. Methods In this open-label study, 19 Japanese CAPS patients aged =2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight = 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24. Results A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study. Conclusion Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.

AB - Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary auto-inflammatory disease, is associated with mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1 β) release. CAPS generally occurs in early childhood with most patients presenting with periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss and optic neuritis. Canakinumab, a fully human anti-IL-1β monoclonal antibody which binds selectively to IL-1β, has demonstrated good efficacy with CAPS. This is the first study to evaluate the safety and efficacy of canakinumab in Japanese patients with CAPS. Methods In this open-label study, 19 Japanese CAPS patients aged =2 years received canakinumab either 150 mg s.c. or 2 mg/kg for patients with a body weight = 40 kg every 8 weeks for 24 weeks. The primary objective was to assess the proportion of patients who were free of relapse at week 24. Results A complete response was achieved in 18 (94.7%) patients with some requiring a dose and/or a frequency adjustment to attain full clinical response. The majority of patients (14/18; 77.8%) were in remission, i.e. free of relapse at week 24. Auto-inflammatory disease activity as assessed by physician's global assessment declined from baseline to end of the study (score of absent in 10.5% at baseline versus 31.6% at end of the study). Two patients had serious adverse events (SAEs), which resolved with standard treatment. One patient reported a mild injection-site reaction. No malignancies or deaths were reported during the study. Conclusion Canakinumab 150 mg s.c. every 8 weeks was well-tolerated, highly efficacious and offered a convenient dosing regimen for treating Japanese patients with CAPS.

UR - http://www.scopus.com/inward/record.url?scp=84875796225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875796225&partnerID=8YFLogxK

M3 - Article

VL - 31

SP - 302

EP - 309

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

SN - 0392-856X

IS - 2

ER -