title: A randomized double-blind trial of intravenous immunoglobulin for pemphigus.
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 (> or =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.
  
  
  CONCLUSIONS
  Prednisolone at 20 mg/d or more may not be high enough to define steroid resistance.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hajime
authors.initials: H
authors.lastname: Iizuka
authors.forename: Katsumi
authors.initials: K
authors.lastname: Hanada
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.forename: Fumio
authors.initials: F
authors.lastname: Kaneko
authors.forename: Seiichi
authors.initials: S
authors.lastname: Izaki
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Zenro
authors.initials: Z
authors.lastname: Ikezawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Seishima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Horiguchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Fukumi
authors.initials: F
authors.lastname: Furukawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hide
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Takeji
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors