Discrepancy Between Clinical and Radiological Responses to Tocilizumab Treatment in Patients with Systemic-onset Juvenile Idiopathic Arthritis

被引:20
作者
Aoki, Chie [1 ]
Inaba, Yutaka [1 ]
Choe, Hyonmin [1 ]
Kaneko, Utako [2 ]
Hara, Ryoki [2 ]
Miyamae, Takako [2 ]
Imagawa, Tomoyuki [2 ]
Mori, Masaaki [2 ]
Oba, Mari S. [3 ]
Yokota, Shumpei [2 ]
Saito, Tomoyuki [1 ]
机构
[1] Yokohama City Univ, Dept Orthoped Surg, Yokohama, Kanagawa 2360004, Japan
[2] Yokohama City Univ, Dept Pediat, Yokohama, Kanagawa 2360004, Japan
[3] Yokohama City Univ, Dept Biostat & Epidemiol, Yokohama, Kanagawa 2360004, Japan
关键词
SYSTEMIC-ONSET JUVENILE IDIOPATHIC ARTHRITIS; TOCILIZUMAB; RADIOGRAPHY; LARSEN SCORE; POZNANSKI SCORE; HIP JOINT; RADIOGRAPHIC PROGRESSION; RHEUMATOID-ARTHRITIS; LARGE JOINTS; DOUBLE-BLIND; CHILDREN; IMPROVEMENT; EFFICACY; ANTIBODY; SCORE;
D O I
10.3899/jrheum.130924
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Conclusion. 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.
引用
收藏
页码:1171 / 1177
页数:7
相关论文
共 24 条
[1]   Serum Matrix Metalloproteinase-3 in Comparison with Acute Phase Proteins as a Marker of Disease Activity and Radiographic Damage in Early Rheumatoid Arthritis [J].
Ally, Mahmood M. T. M. ;
Hodkinson, Bridget ;
Meyer, Pieter W. A. ;
Musenge, Eustasius ;
Tikly, Mohammed ;
Anderson, Ronald .
MEDIATORS OF INFLAMMATION, 2013, 2013
[2]   Development and Initial Validation of a Radiographic Scoring System for the Hip in Juvenile Idiopathic Arthritis [J].
Bertamino, Marta ;
Rossi, Federica ;
Pistorio, Angela ;
Lucigrai, Giorgio ;
Valle, Maura ;
Viola, Stefania ;
Magni-Manzoni, Silvia ;
Malattia, Clara ;
Martini, Alberto ;
Ravelli, Angelo .
JOURNAL OF RHEUMATOLOGY, 2010, 37 (02) :432-439
[3]   Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis [J].
De Benedetti, Fabrizio ;
Brunner, Hermine I. ;
Ruperto, Nicolino ;
Kenwright, Andrew ;
Wright, Stephen ;
Calvo, Inmaculada ;
Cuttica, Ruben ;
Ravelli, Angelo ;
Schneider, Rayfel ;
Woo, Patricia ;
Wouters, Carine ;
Xavier, Ricardo ;
Zemel, Lawrence ;
Baildam, Eileen ;
Burgos-Vargas, Ruben ;
Dolezalova, Pavla ;
Garay, Stella M. ;
Merino, Rosa ;
Joos, Rik ;
Grom, Alexei ;
Wulffraat, Nico ;
Zuber, Zbigniew ;
Zulian, Francesco ;
Lovell, Daniel ;
Martini, Alberto .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (25) :2385-2395
[4]   The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis [J].
Gattorno, Marco ;
Piccini, Alessandra ;
Lasiglie, Denise ;
Tassi, Sara ;
Brisca, Giacomo ;
Carta, Sonia ;
Delfino, Laura ;
Ferlito, Francesca ;
Pelagatti, Maria Antonietta ;
Caroli, Francesco ;
Buoncompagni, Antonella ;
Viola, Stefania ;
Loy, Anna ;
Sironi, Marina ;
Vecchi, Annunciata ;
Ravelli, Angelo ;
Martini, Alberto ;
Rubartelli, Anna .
ARTHRITIS AND RHEUMATISM, 2008, 58 (05) :1505-1515
[5]  
Giannini EH, 1997, ARTHRITIS RHEUM, V40, P1202
[6]   EFFECTS OF METHOTREXATE ON RADIOLOGIC PROGRESSION IN JUVENILE RHEUMATOID-ARTHRITIS [J].
HAREL, L ;
WAGNERWEINER, L ;
POZNANSKI, AK ;
SPENCER, CH ;
EKWO, E ;
MAGILAVY, DB .
ARTHRITIS AND RHEUMATISM, 1993, 36 (10) :1370-1374
[7]   Radiologic analysis of the effect of tocilizumab on hands and large joints in children with systemic juvenile idiopathic arthritis [J].
Inaba, Yutaka ;
Ozawa, Remi ;
Aoki, Chie ;
Imagawa, Tomoyuki ;
Mori, Masaaki ;
Hara, Ryoki ;
Miyamae, Takako ;
Saito, Tomoyuki ;
Yokota, Shumpei .
MODERN RHEUMATOLOGY, 2013, 23 (04) :667-673
[8]   Radiographic improvement of damaged large joints in children with systemic juvenile idiopathic arthritis following tocilizumab treatment [J].
Inaba, Yutaka ;
Ozawa, Remi ;
Imagawa, Tomoyuki ;
Mori, Masaaki ;
Hara, Yoshinori ;
Miyamae, Takako ;
Aoki, Chie ;
Saito, Tomoyuki ;
Yokota, Shumpei .
ANNALS OF THE RHEUMATIC DISEASES, 2011, 70 (09) :1693-U395
[9]  
LARSEN A, 1995, J RHEUMATOL, V22, P1974
[10]   Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab [J].
Nakajima, Shoko ;
Naruto, Takuya ;
Miyamae, Takako ;
Imagawa, Tomoyuki ;
Mori, Masaaki ;
Nishimaki, Shigeru ;
Yokota, Shumpei .
MODERN RHEUMATOLOGY, 2009, 19 (01) :42-46