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: Miyamoto Takayuki , Izawa Kazushi , Masui Sho , Yamazaki Atsue , Yamasaki Yuichi , Matsubayashi Tadashi , Shiraki Mayuka , Ohnishi Hidenori , Yasumura Junko , Kawabe Tomohiro , Miyamae Takako , Matsubara Tomoyo , Arakawa Naoya , Ishige Takashi , Takizawa Takumi , Shimbo Asami , Shimizu Masaki , Kimura Naoki , Maeda Yuichi , Maruyama Yuta , Shigemura Tomonari , Furuta Junichi , Sato Satoshi , Tanaka Hiroshi , Izumikawa Miharu , Yamamura Masahiro , Hasegawa Toshio , Kaneko Hiroshi , Nakagishi Yasuo , Nakano Naoko , Iida Yasunori , Nakamura Tamaki , Wakiguchi Hiroyuki , Hoshina Takayuki , Kawai Toshinao , Murakami Kosaku , Akizuki Shuji , Morinobu Akio , Ohmura Koichiro , Eguchi Katsuhide , Sonoda Motoshi , Ishimura Masataka , Furuno Kenji , Kashiwado Momoko , Mori Masaaki , Kawahata Kimito , Hayama Koremasa , Shimoyama Kumiko , Sasaki Natsuko , Ito Taisuke , Umebayashi Hiroaki , Omori Tae , Nakamichi Seiko , Dohmoto Tomotsune , Hasegawa Yasuyuki , Kawashima Hisashi , Watanabe Shojiro , Taguchi Yuichiro , Nakaseko Haruna , Iwata Naomi , Kohno Hiroki , Ando Taiki , Ito Yasuhiko , Kataoka Yuko , Saeki Takako , Kaneko Utako , Murase Ayako , Hattori Seira , Nozawa Tomo , Nishimura Kenichi , Nakano Reiji , Watanabe Misa , Yashiro Masato , Nakamura Tomonori , Komai Toshihiko , Kato Kentaro , Honda Yoshitaka , Hiejima Eitaro , Yonezawa Atsushi , Bessho Kazuhisa , Okada Satoshi , Ohara Osamu , Takita Junko , Yasumi Takahiro , Nishikomori Ryuta ,   the Japan CAPS Working Group
Published: January 2024

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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