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 HideYoshiki Tokura, Masutaka Furue, Takashi Hashimoto, Hironobu Ihn, Sakuhei Fujiwara, Takeji Nishikawa, Hideoki Ogawa, Yasuo Kitajima, Koji Hashimoto

Research output: Contribution to journalArticlepeer-review

220 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2009 Apr

ASJC Scopus subject areas

  • Dermatology


Dive into the research topics of 'A randomized double-blind trial of intravenous immunoglobulin for pemphigus'. Together they form a unique fingerprint.

Cite this