Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease.
Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.
Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. norihiro@fbs.osaka-u.ac.jp
Norihiro
N
Nishimoto
Yuzuru
Y
Kanakura
Katsuyuki
K
Aozasa
Takeshi
T
Johkoh
Minoru
M
Nakamura
Shuji
S
Nakano
Nobuaki
N
Nakano
Yasuo
Y
Ikeda
Takeshi
T
Sasaki
Kiyoshi
K
Nishioka
Masamichi
M
Hara
Hirokuni
H
Taguchi
Yukihiko
Y
Kimura
Yoshiro
Y
Kato
Hideki
H
Asaoku
Shunichi
S
Kumagai
Fumio
F
Kodama
Hideko
H
Nakahara
Keisuke
K
Hagihara
Kazuyuki
K
Yoshizaki
Tadamitsu
T
Kishimoto
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D005871:Castleman Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D016896:Treatment Outcome
D000906:Antibodies; D019947:Receptors, Interleukin-6