Discrepancy between clinical and radiological responses to tocilizumab treatment in patients with systemic-onset juvenile idiopathic arthritis.
OBJECTIVE
Tocilizumab (TCZ), an antiinterleukin-6 receptor monoclonal antibody, is clinically beneficial in patients with systemic-onset juvenile idiopathic arthritis (sJIA). We investigated the clinical and radiological outcomes of TCZ therapy in patients with sJIA.


METHODS
We retrospectively evaluated 2 clinical trials (NCT00144599 and NCT00144612) involving 40 patients with sJIA who received intravenous TCZ (8 mg/kg) every 2 weeks. Clinical data and radiographs of the hands and large joints were assessed before and during TCZ treatment. The Poznanski score, modified Larsen scores of the hands and large joints, and Childhood Arthritis Radiographic Score of the Hip (CARSH) were recorded.


RESULTS
After a mean duration of 4.5 years of TCZ treatment, clinical data had improved significantly, the mean Poznanski score improved from -1.5 to -1.1, the mean Larsen score of the hands deteriorated from 7.0 to 10.0, the mean Larsen score for the large joints deteriorated from 5.9 to 6.8, and the CARSH worsened from 3.9 to 6.2. The Larsen score for the large joints improved in 11 cases (28%), remained unchanged in 8 cases (20%), and worsened in 21 cases (52%). Matrix metalloproteinase 3 (MMP-3) levels remained significantly higher (278 mg/dl) in patients with worsened Larsen scores than in patients with improved or unchanged scores (65 mg/dl). Logistic regression analysis showed that older age at disease onset was a significant risk factor for radiographic progression.


CONCLUSIONS
The modified Larsen score of the large joints deteriorated in half the patients who had high MMP-3 levels during TCZ treatment and who were significantly older at disease onset.
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Chie
C
Aoki
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University. yute0131@med.yokohama-cu.ac.jp.
Yutaka
Y
Inaba
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Hyonmin
H
Choe
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Utako
U
Kaneko
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Ryoki
R
Hara
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Takako
T
Miyamae
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Tomoyuki
T
Imagawa
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Masaaki
M
Mori
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Mari S
MS
Oba
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Shumpei
S
Yokota
From the Department of Orthopedic Surgery, the Department of Pediatrics, and the Department of Biostatistics and Epidemiology, Yokohama City University, Yokohama, Japan.C. Aoki, MD; Y. Inaba, MD, PhD, Associate Professor; H. Choe, MD, PhD, Department of Orthopedic Surgery; U. Kaneko, MD; R. Hara, MD, PhD; T. Miyamae, MD, PhD; T. Imagawa, MD, PhD; M. Mori, MD, PhD, Associate Professor, Department of Pediatrics; M.S. Oba, Department of Biostatistics and Epidemiology; S. Yokota, MD, Professor of Pediatrics, Department of Pediatrics; T. Saito, MD, Professor of Orthopedics, Department of Orthopedic Surgery, Yokohama City University.
Tomoyuki
T
Saito
D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D050823:Hand Joints / Q000000981:diagnostic imaging* / Q000187:drug effects; D006621:Hip Joint / Q000000981:diagnostic imaging* / Q000187:drug effects; D006801:Humans; D008297:Male; D011859:Radiography; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
HIP JOINT; LARSEN SCORE; POZNANSKI SCORE; RADIOGRAPHY; SYSTEMIC-ONSET JUVENILE IDIOPATHIC ARTHRITIS; TOCILIZUMAB