A randomized double-blind trial of intravenous immunoglobulin for pemphigus

Masayuki Amagai, Shigaku Ikeda, Hiroshi Shimizu, Hajime Iizuka, Katsumi Hanada, Setsuya Aiba, Fumio Kaneko, Seiichi Izaki, Kunihiko Tamaki, Zenro Ikezawa, Masahiro Takigawa, Mariko Seishima, Toshihiro Tanaka, Yoshiki Miyachi, Ichiro Katayama, Yuji Horiguchi, Sachiko Miyagawa, Fukumi Furukawa, Keiji Iwatsuki, Michihiro Hide & 9 others Yoshiki Tokura, Masutaka Furue, Takashi Hashimoto, Hironobu Ihn, Sakuhei Fujiwara, Takeji Nishikawa, Hideoki Ogawa, Yasuo Kitajima, Koji Hashimoto

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Background: Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a placebo group, appropriate treatment often must be provided when the disease flares. Objective: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of a single cycle of high-dose intravenous immunoglobulin (400, 200, or 0 mg/kg/d) administered over 5 consecutive days in patients relatively resistant to systemic steroids. Methods: We evaluated efficacy with time to escape from the protocol as a novel primary end point, and pemphigus activity score, antidesmoglein enzyme-linked immunosorbent assay scores, and safety as secondary end points. Results: We enrolled 61 patients with pemphigus vulgaris or pemphigus foliaceus who did not respond to prednisolone (≥20 mg/d). Time to escape from the protocol was significantly prolonged in the 400-mg group compared with the placebo group (P <.001), and a dose-response relationship among the 3 treatment groups was observed (P <.001). Disease activity and enzyme-linked immunosorbent assay scores were significantly lower in the 400-mg group than in the other groups (P <.05 on day 43, P <.01 on day 85). There was no significant difference in the safety end point among the 3 treatment groups. Limitation: Prednisolone at 20 mg/d or more may not be high enough to define steroid resistance. Conclusion: Intravenous immunoglobulin (400 mg/kg/d for 5 d) in a single cycle is an effective and safe treatment for patients with pemphigus who are relatively resistant to systemic steroids. Time to escape from the protocol is a useful indicator for evaluation in randomized, placebo-controlled, double-blind studies of rare and serious diseases.

Original languageEnglish
Pages (from-to)595-603
Number of pages9
JournalJournal of the American Academy of Dermatology
Volume60
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Pemphigus
Intravenous Immunoglobulins
Placebos
Steroids
Prednisolone
Double-Blind Method
Desmogleins
Enzyme-Linked Immunosorbent Assay
Safety
Therapeutic Uses
Therapeutics
Rare Diseases
Autoantibodies
Autoimmune Diseases
Immunoglobulin G

ASJC Scopus subject areas

  • Dermatology

Cite this

Amagai, M., Ikeda, S., Shimizu, H., Iizuka, H., Hanada, K., Aiba, S., ... Hashimoto, K. (2009). A randomized double-blind trial of intravenous immunoglobulin for pemphigus. Journal of the American Academy of Dermatology, 60(4), 595-603. https://doi.org/10.1016/j.jaad.2008.09.052

A randomized double-blind trial of intravenous immunoglobulin for pemphigus. / Amagai, Masayuki; Ikeda, Shigaku; Shimizu, Hiroshi; Iizuka, Hajime; Hanada, Katsumi; Aiba, Setsuya; Kaneko, Fumio; Izaki, Seiichi; Tamaki, Kunihiko; Ikezawa, Zenro; Takigawa, Masahiro; Seishima, Mariko; Tanaka, Toshihiro; Miyachi, Yoshiki; Katayama, Ichiro; Horiguchi, Yuji; Miyagawa, Sachiko; Furukawa, Fukumi; Iwatsuki, Keiji; Hide, Michihiro; Tokura, Yoshiki; Furue, Masutaka; Hashimoto, Takashi; Ihn, Hironobu; Fujiwara, Sakuhei; Nishikawa, Takeji; Ogawa, Hideoki; Kitajima, Yasuo; Hashimoto, Koji.

In: Journal of the American Academy of Dermatology, Vol. 60, No. 4, 04.2009, p. 595-603.

Research output: Contribution to journalArticle

Amagai, M, Ikeda, S, Shimizu, H, Iizuka, H, Hanada, K, Aiba, S, Kaneko, F, Izaki, S, Tamaki, K, Ikezawa, Z, Takigawa, M, Seishima, M, Tanaka, T, Miyachi, Y, Katayama, I, Horiguchi, Y, Miyagawa, S, Furukawa, F, Iwatsuki, K, Hide, M, Tokura, Y, Furue, M, Hashimoto, T, Ihn, H, Fujiwara, S, Nishikawa, T, Ogawa, H, Kitajima, Y & Hashimoto, K 2009, 'A randomized double-blind trial of intravenous immunoglobulin for pemphigus', Journal of the American Academy of Dermatology, vol. 60, no. 4, pp. 595-603. https://doi.org/10.1016/j.jaad.2008.09.052
Amagai, Masayuki ; Ikeda, Shigaku ; Shimizu, Hiroshi ; Iizuka, Hajime ; Hanada, Katsumi ; Aiba, Setsuya ; Kaneko, Fumio ; Izaki, Seiichi ; Tamaki, Kunihiko ; Ikezawa, Zenro ; Takigawa, Masahiro ; Seishima, Mariko ; Tanaka, Toshihiro ; Miyachi, Yoshiki ; Katayama, Ichiro ; Horiguchi, Yuji ; Miyagawa, Sachiko ; Furukawa, Fukumi ; Iwatsuki, Keiji ; Hide, Michihiro ; Tokura, Yoshiki ; Furue, Masutaka ; Hashimoto, Takashi ; Ihn, Hironobu ; Fujiwara, Sakuhei ; Nishikawa, Takeji ; Ogawa, Hideoki ; Kitajima, Yasuo ; Hashimoto, Koji. / A randomized double-blind trial of intravenous immunoglobulin for pemphigus. In: Journal of the American Academy of Dermatology. 2009 ; Vol. 60, No. 4. pp. 595-603.
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abstract = "Background: Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a placebo group, appropriate treatment often must be provided when the disease flares. Objective: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of a single cycle of high-dose intravenous immunoglobulin (400, 200, or 0 mg/kg/d) administered over 5 consecutive days in patients relatively resistant to systemic steroids. Methods: We evaluated efficacy with time to escape from the protocol as a novel primary end point, and pemphigus activity score, antidesmoglein enzyme-linked immunosorbent assay scores, and safety as secondary end points. Results: We enrolled 61 patients with pemphigus vulgaris or pemphigus foliaceus who did not respond to prednisolone (≥20 mg/d). Time to escape from the protocol was significantly prolonged in the 400-mg group compared with the placebo group (P <.001), and a dose-response relationship among the 3 treatment groups was observed (P <.001). Disease activity and enzyme-linked immunosorbent assay scores were significantly lower in the 400-mg group than in the other groups (P <.05 on day 43, P <.01 on day 85). There was no significant difference in the safety end point among the 3 treatment groups. Limitation: Prednisolone at 20 mg/d or more may not be high enough to define steroid resistance. Conclusion: Intravenous immunoglobulin (400 mg/kg/d for 5 d) in a single cycle is an effective and safe treatment for patients with pemphigus who are relatively resistant to systemic steroids. Time to escape from the protocol is a useful indicator for evaluation in randomized, placebo-controlled, double-blind studies of rare and serious diseases.",
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AU - Amagai, Masayuki

AU - Ikeda, Shigaku

AU - Shimizu, Hiroshi

AU - Iizuka, Hajime

AU - Hanada, Katsumi

AU - Aiba, Setsuya

AU - Kaneko, Fumio

AU - Izaki, Seiichi

AU - Tamaki, Kunihiko

AU - Ikezawa, Zenro

AU - Takigawa, Masahiro

AU - Seishima, Mariko

AU - Tanaka, Toshihiro

AU - Miyachi, Yoshiki

AU - Katayama, Ichiro

AU - Horiguchi, Yuji

AU - Miyagawa, Sachiko

AU - Furukawa, Fukumi

AU - Iwatsuki, Keiji

AU - Hide, Michihiro

AU - Tokura, Yoshiki

AU - Furue, Masutaka

AU - Hashimoto, Takashi

AU - Ihn, Hironobu

AU - Fujiwara, Sakuhei

AU - Nishikawa, Takeji

AU - Ogawa, Hideoki

AU - Kitajima, Yasuo

AU - Hashimoto, Koji

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