Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis.
OBJECTIVE
To investigate the safety and efficacy of a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL-6 in children with systemic-onset juvenile idiopathic arthritis (JIA) refractory to high-dose, long-term corticosteroids.


METHODS
An individual escalating-dose trial was conducted in 11 children with active systemic-onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4-mg/kg dose. Those without disease flares at this dose received a second 4-mg/kg dose 2 weeks later and a third 4-mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests.


RESULTS
MRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute-phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response.


CONCLUSIONS
MRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute-phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL-6 and adverse events.
Yokota
Shumpei
S
Yokohama City University School of Medicine, Kanagawa, Japan. syokota@med.yokohama-cu.ac.jp <syokota@med.yokohama-cu.ac.jp>
Miyamae
Takako
T
Imagawa
Tomoyuki
T
Iwata
Naomi
N
Katakura
Shigeki
S
Mori
Masaaki
M
Woo
Patricia
P
Nishimoto
Norihiro
N
Yoshizaki
Kazuyuki
K
Kishimoto
Tadamitsu
T
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000276:immunology; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D016896:Treatment Outcome
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D019947:Receptors, Interleukin-6