Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey

Takayuki Miyamoto¹, Kazushi Izawa¹, Sho Masui¹, Atsue Yamazaki¹, Yuichi Yamasaki², Tadashi Matsubayashi³, Mayuka Shiraki⁴, Hidenori Ohnishi⁴, Junko Yasumura⁵, Tomohiro Kawabe⁶, Takako Miyamae⁶, Tomoyo Matsubara⁷, Naoya Arakawa⁸, Takashi Ishige⁸, Takumi Takizawa⁸, Asami Shimbo⁹, Masaki Shimizu⁹, Naoki Kimura⁹, Yuichi Maeda¹⁰, Yuta Maruyama¹¹, Tomonari Shigemura¹¹, Junichi Furuta¹², Satoshi Sato¹³, Hiroshi Tanaka¹⁴, Miharu Izumikawa¹⁵, Masahiro Yamamura¹⁶, Toshio Hasegawa¹⁷, Hiroshi Kaneko¹⁸, Yasuo Nakagishi¹⁹, Naoko Nakano²⁰, Yasunori Iida²¹, Tamaki Nakamura²¹, Hiroyuki Wakiguchi²¹, Takayuki Hoshina²², Toshinao Kawai²³, Kosaku Murakami¹, Shuji Akizuki¹, Akio Morinobu¹, Koichiro Ohmura²⁴, Katsuhide Eguchi²⁵, Motoshi Sonoda²⁵, Masataka Ishimura²⁵, Kenji Furuno²⁶, Momoko Kashiwado²⁷, Masaaki Mori²⁸, Kimito Kawahata²⁷, Koremasa Hayama²⁹, Kumiko Shimoyama³⁰, Natsuko Sasaki²², Taisuke Ito³⁰, Hiroaki Umebayashi³¹, Tae Omori³², Seiko Nakamichi³³, Tomotsune Dohmoto³⁴, Yasuyuki Hasegawa³⁴, Hisashi Kawashima³⁵, Shojiro Watanabe³⁶, Yuichiro Taguchi³⁷, Haruna Nakaseko³⁸, Naomi Iwata³⁸, Hiroki Kohno⁶, Taiki Ando¹⁷, Yasuhiko Ito³⁹, Yuko Kataoka⁴⁰, Takako Saeki⁴¹, Utako Kaneko⁴², Ayako Murase⁴³, Seira Hattori⁴³, Tomo Nozawa⁴³, Kenichi Nishimura⁴³, Reiji Nakano⁴⁴, Misa Watanabe⁴⁵, Masato Yashiro⁴⁶, Tomonori Nakamura⁴⁷, Toshihiko Komai⁴⁸, Kentaro Kato¹, Yoshitaka Honda¹, Eitaro Hiejima¹, Atsushi Yonezawa¹, Kazuhisa Bessho¹, Satoshi Okada⁵, Osamu Ohara⁴⁹, Junko Takita¹, Takahiro Yasumi¹, Ryuta Nishikomori⁵⁰; Japan CAPS Working Group

Collaborators, Affiliations

Collaborators

Japan CAPS Working Group:
Shigeaki Nonoyama, Kohsuke Imai, Shuichi Ito, Nobuo Kanazawa, Naotomo Kambe, Hidetoshi Takada, Takashi Yamazaki, Syuji Takei, Fumiko Ozaki, Tomoko Iehara, Tetsuo Kubota, Mitsuru Tsuge, Norimoto Kobayashi, Atsuo Taniguchi, Kiyoshi Kawakami, Kenji Nakagawa

Affiliations

¹ Kyoto University, Kyoto, Japan.
² Kagoshima University Hospital, Kagoshima, Japan.
³ Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
⁴ Gifu University, Gifu, Japan.
⁵ Hiroshima University, Hiroshima, Japan.
⁶ Tokyo Women's Medical University Hospital, Tokyo, Japan.
⁷ Dokkyo Medical University Saitama Medical Center, Saitama, Japan.
⁸ Gunma University, Maebashi, Japan.
⁹ Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰ Osaka University, Suita, Japan.
¹¹ Shinshu University, Matsumoto, Japan.
¹² University of Tsukuba, Tsukuba, Japan.
¹³ Saitama Children's Medical Center, Saitama, Japan.
¹⁴ Hirosaki University Hospital, Hirosaki, Japan.
¹⁵ Kagawa University, Kagawa, Japan.
¹⁶ Okayama Saiseikai General Hospital, Okayama, Japan.
¹⁷ Juntendo University, Tokyo, Japan.
¹⁸ National Center for Global Health and Medicine, Tokyo, Japan.
¹⁹ Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
²⁰ Ehime Prefectural Central Hospital, Matsuyama, Japan.
²¹ Yamaguchi University, Ube, Japan.
²² University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
²³ National Center for Child Health and Development, Tokyo, Japan.
²⁴ Kobe City Medical Center General Hospital, Kobe, Japan.
²⁵ Kyushu University, Fukuoka, Japan.
²⁶ Fukuoka Children's Hospital, Fukuoka, Japan.
²⁷ St. Marianna University School of Medicine, Kawasaki, Japan.
²⁸ Tokyo Medical and Dental University, Tokyo, Japan, and St. Marianna University School of Medicine, Kawasaki, Japan.
²⁹ Nihon University, Tokyo, Japan.
³⁰ Hamamatsu University School of Medicine, Hamamatsu, Japan.
³¹ Miyagi Children's Hospital, Sendai, Japan.
³² Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
³³ Nagasaki University, Nagasaki, Japan.
³⁴ Tottori Prefectural Central Hospital, Tottori, Japan.
³⁵ Tokyo Medical University, Tokyo, Japan.
³⁶ Ehime University, Matsuyama, Japan.
³⁷ Department of Rheumatology, Nagoya Ekisaikai Hospital, Nagoya, Japan.
³⁸ Aichi Children's Health and Medical Center, Obu, Japan.
³⁹ Nagoya City University West Medical Center, Nagoya, Japan.
⁴⁰ Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁴¹ Nagaoka Red Cross Hospital, Nagaoka, Japan.
⁴² Niigata University, Niigata, Japan.
⁴³ Yokohama City University, Yokohama, Japan.
⁴⁴ Shizuoka Children's Hospital, Shizuoka, Japan.
⁴⁵ Toho University, Tokyo, Japan.
⁴⁶ Okayama University Hospital, Okayama, Japan.
⁴⁷ Kagoshima University, Kagoshima, Japan.
⁴⁸ The University of Tokyo, Tokyo, Japan.
⁴⁹ Kazusa DNA Research Institute, Kisarazu, Japan.
⁵⁰ Kurume University, Kurume, Japan.

PMID: 38268504
DOI: 10.1002/art.42808

Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey

Takayuki Miyamoto et al. Arthritis Rheumatol. 2024 Jun.

. 2024 Jun;76(6):949-962.

doi: 10.1002/art.42808. Epub 2024 Mar 7.

Authors

Collaborators

Japan CAPS Working Group:
Shigeaki Nonoyama, Kohsuke Imai, Shuichi Ito, Nobuo Kanazawa, Naotomo Kambe, Hidetoshi Takada, Takashi Yamazaki, Syuji Takei, Fumiko Ozaki, Tomoko Iehara, Tetsuo Kubota, Mitsuru Tsuge, Norimoto Kobayashi, Atsuo Taniguchi, Kiyoshi Kawakami, Kenji Nakagawa

Affiliations

¹ Kyoto University, Kyoto, Japan.
² Kagoshima University Hospital, Kagoshima, Japan.
³ Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
⁴ Gifu University, Gifu, Japan.
⁵ Hiroshima University, Hiroshima, Japan.
⁶ Tokyo Women's Medical University Hospital, Tokyo, Japan.
⁷ Dokkyo Medical University Saitama Medical Center, Saitama, Japan.
⁸ Gunma University, Maebashi, Japan.
⁹ Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰ Osaka University, Suita, Japan.
¹¹ Shinshu University, Matsumoto, Japan.
¹² University of Tsukuba, Tsukuba, Japan.
¹³ Saitama Children's Medical Center, Saitama, Japan.
¹⁴ Hirosaki University Hospital, Hirosaki, Japan.
¹⁵ Kagawa University, Kagawa, Japan.
¹⁶ Okayama Saiseikai General Hospital, Okayama, Japan.
¹⁷ Juntendo University, Tokyo, Japan.
¹⁸ National Center for Global Health and Medicine, Tokyo, Japan.
¹⁹ Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
²⁰ Ehime Prefectural Central Hospital, Matsuyama, Japan.
²¹ Yamaguchi University, Ube, Japan.
²² University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
²³ National Center for Child Health and Development, Tokyo, Japan.
²⁴ Kobe City Medical Center General Hospital, Kobe, Japan.
²⁵ Kyushu University, Fukuoka, Japan.
²⁶ Fukuoka Children's Hospital, Fukuoka, Japan.
²⁷ St. Marianna University School of Medicine, Kawasaki, Japan.
²⁸ Tokyo Medical and Dental University, Tokyo, Japan, and St. Marianna University School of Medicine, Kawasaki, Japan.
²⁹ Nihon University, Tokyo, Japan.
³⁰ Hamamatsu University School of Medicine, Hamamatsu, Japan.
³¹ Miyagi Children's Hospital, Sendai, Japan.
³² Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
³³ Nagasaki University, Nagasaki, Japan.
³⁴ Tottori Prefectural Central Hospital, Tottori, Japan.
³⁵ Tokyo Medical University, Tokyo, Japan.
³⁶ Ehime University, Matsuyama, Japan.
³⁷ Department of Rheumatology, Nagoya Ekisaikai Hospital, Nagoya, Japan.
³⁸ Aichi Children's Health and Medical Center, Obu, Japan.
³⁹ Nagoya City University West Medical Center, Nagoya, Japan.
⁴⁰ Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁴¹ Nagaoka Red Cross Hospital, Nagaoka, Japan.
⁴² Niigata University, Niigata, Japan.
⁴³ Yokohama City University, Yokohama, Japan.
⁴⁴ Shizuoka Children's Hospital, Shizuoka, Japan.
⁴⁵ Toho University, Tokyo, Japan.
⁴⁶ Okayama University Hospital, Okayama, Japan.
⁴⁷ Kagoshima University, Kagoshima, Japan.
⁴⁸ The University of Tokyo, Tokyo, Japan.
⁴⁹ Kazusa DNA Research Institute, Kisarazu, Japan.
⁵⁰ Kurume University, Kurume, Japan.

PMID: 38268504
DOI: 10.1002/art.42808

Abstract

Objective: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab.

Methods: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed.

Results: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy.

Conclusion: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment.

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References

REFERENCES

1. Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin‐like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome. Nat Genet 2001;29:301–305.
1. Hoffman HM, Wanderer AA, Broide DH. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 2001;108:615–620.
1. Finetti M, Omenetti A, Federici S, et al. Chronic infantile neurological cutaneous and articular (CINCA) syndrome: a review. Orphanet J Rare Dis 2016;11:167.
1. Tran TA. Muckle–Wells syndrome: clinical perspectives. Open Access Rheumatol 2017;9:123–129.
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Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey

Collaborators

Affiliations

Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey

Authors

Collaborators

Affiliations

Abstract

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REFERENCES

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