A randomized double-blind trial of intravenous immunoglobulin for pemphigus.
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.
Amagai
Masayuki
M
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Ikeda
Shigaku
S
Shimizu
Hiroshi
H
Iizuka
Hajime
H
Hanada
Katsumi
K
Aiba
Setsuya
S
Kaneko
Fumio
F
Izaki
Seiichi
S
Tamaki
Kunihiko
K
Ikezawa
Zenro
Z
Takigawa
Masahiro
M
Seishima
Mariko
M
Tanaka
Toshihiro
T
Miyachi
Yoshiki
Y
Katayama
Ichiro
I
Horiguchi
Yuji
Y
Miyagawa
Sachiko
S
Furukawa
Fukumi
F
Iwatsuki
Keiji
K
Hide
Michihiro
M
Tokura
Yoshiki
Y
Furue
Masutaka
M
Hashimoto
Takashi
T
Ihn
Hironobu
H
Fujiwara
Sakuhei
S
Nishikawa
Takeji
T
Ogawa
Hideoki
H
Kitajima
Yasuo
Y
Hashimoto
Koji
K
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
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors