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Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease

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Abstract

Background and Objectives

Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD.

Methods

We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score.

Results

Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group.

Conclusions

The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA.

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Acknowledgements

We thank the following current and ex-members of the Shizuoka Kawasaki Disease Study Group for their cooperation in carrying out the study. We also thank Takaaki Megro, MD, Shizuoka Children`s Hospital; Tutomu Kamimaki, MD, Shizuoka City Shimizu Hospital; Tomoko Kawasaki, MD, Seirei Numazu Hospital; Toshihiro Tanaka, MD, Shizuoka Kosei Hospital; Ichiro Ohkawara, MD, Shizuoka Red Cross Hospital; Nobutaka Shimizu, MD, Yaizu City Hospital; Kou Asakura, MD, Fujieda Muncipal General Hospital, and Mituaki Kimura, PhD, former chairman of the Shizuoka Kawasaki Disease Study Group for their assistance in the treatment of the patients.

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Authors and Affiliations

  1. The Shizuoka Kawasaki Disease Study Group, Shizuoka, Japan

    Hidemasa Sakai, Satoru Iwashima, Shinichiro Sano, Naoe Akiyama, Eiko Nagata, Masashi Harazaki & Tetuya Fukuoka

  2. Department of Pediatrics, Shizuoka City Shizuoka Hospital, Shizuoka, Japan

    Hidemasa Sakai

  3. Department of Pediatrics, Chutoen General Medical Center, Kakegawa, Japan

    Satoru Iwashima

  4. Department of Pediatrics, Hamamatsu Medical Center, Shizuoka, Japan

    Shinichiro Sano

  5. Department of Pediatrics, Fuji City General Hospital, Shizuoka, Japan

    Naoe Akiyama

  6. Center for Clinical Research, Hamamatsu University Hospital, Shizuoka, Japan

    Eiko Nagata

  7. Department of Pediatrics, Medical Genetics, Shizuoka General Hospital, Shizuoka, Japan

    Masashi Harazaki

  8. Department of Pediatrics, Medical Genetics, Shizuoka Saiseikai General Hospital, Shizuoka, Japan

    Tetuya Fukuoka

Authors
  1. Hidemasa Sakai
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  2. Satoru Iwashima
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  4. Naoe Akiyama
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  7. Tetuya Fukuoka
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Corresponding author

Correspondence to Satoru Iwashima.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author contributions

All authors made substantial contributions to the conception of the study. All authors read and approved the final manuscript. H.S., S.I., S.S., and M.H. interpreted the data and wrote the paper.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for profit sectors.

Ethics approval

The study was reviewed and approved by the ethics committee of Shizuoka Children’s Hospital (ID: R000014887) and all participating institutions.

Consent to participate

Patients and their guardians provided written informed consent before enrolment or informed consent was obtained as an opt-out and inclusion agreement based on the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects. Some institutions posted an explanation of this study on their web homepage. When a subject was not willing to participate, his/her data were excluded from the analysis.

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Not applicable.

Availability of data and material

The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.

Code availability

This study was registered as a clinical trial at UMIN (UMIN000025707).

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Sakai, H., Iwashima, S., Sano, S. et al. Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease. Clin Drug Investig 41, 77–88 (2021). https://doi.org/10.1007/s40261-020-00984-6

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