Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis
- Author
- Fabrizio De Benedetti, Hermine I Brunner, Nicolino Ruperto, Andrew Kenwright, Stephen Wright, Inmaculada Calvo, Ruben Cuttica, Angelo Ravelli, Rayfel Schneider, Patricia Woo, Carine Wouters, Ricardo Xavier, Lawrence Zemel, Eileen Baildam, Ruben Burgos-Vargas, Pavla Dolezalova, Stella M Garay, Rosa Merino, Rik Joos, Alexei Grom, Nico Wulffraat, Zbigniew Zuber, Francesco Zulian, Daniel Lovell and Alberto Martini
- Organization
- Abstract
- BACKGROUND Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of >= 6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was >= 30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels.
- Keywords
- ETANERCEPT, CHILDREN, INTERLEUKIN-6, DOUBLE-BLIND, CHRONIC INFLAMMATION, PRELIMINARY DEFINITION, RHEUMATOID-ARTHRITIS, RECEPTOR ANTAGONIST ANAKINRA, DISEASE, SAFETY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-3106416
- MLA
- De Benedetti, Fabrizio, et al. “Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis.” NEW ENGLAND JOURNAL OF MEDICINE, vol. 367, no. 25, 2012, pp. 2385–95, doi:10.1056/NEJMoa1112802.
- APA
- De Benedetti, F., Brunner, H. I., Ruperto, N., Kenwright, A., Wright, S., Calvo, I., … Martini, A. (2012). Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. NEW ENGLAND JOURNAL OF MEDICINE, 367(25), 2385–2395. https://doi.org/10.1056/NEJMoa1112802
- Chicago author-date
- De Benedetti, Fabrizio, Hermine I Brunner, Nicolino Ruperto, Andrew Kenwright, Stephen Wright, Inmaculada Calvo, Ruben Cuttica, et al. 2012. “Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis.” NEW ENGLAND JOURNAL OF MEDICINE 367 (25): 2385–95. https://doi.org/10.1056/NEJMoa1112802.
- Chicago author-date (all authors)
- De Benedetti, Fabrizio, Hermine I Brunner, Nicolino Ruperto, Andrew Kenwright, Stephen Wright, Inmaculada Calvo, Ruben Cuttica, Angelo Ravelli, Rayfel Schneider, Patricia Woo, Carine Wouters, Ricardo Xavier, Lawrence Zemel, Eileen Baildam, Ruben Burgos-Vargas, Pavla Dolezalova, Stella M Garay, Rosa Merino, Rik Joos, Alexei Grom, Nico Wulffraat, Zbigniew Zuber, Francesco Zulian, Daniel Lovell, and Alberto Martini. 2012. “Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis.” NEW ENGLAND JOURNAL OF MEDICINE 367 (25): 2385–2395. doi:10.1056/NEJMoa1112802.
- Vancouver
- 1.De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. NEW ENGLAND JOURNAL OF MEDICINE. 2012;367(25):2385–95.
- IEEE
- [1]F. De Benedetti et al., “Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis,” NEW ENGLAND JOURNAL OF MEDICINE, vol. 367, no. 25, pp. 2385–2395, 2012.
@article{3106416, abstract = {{BACKGROUND Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of >= 6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was >= 30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels.}}, author = {{De Benedetti, Fabrizio and Brunner, Hermine I and Ruperto, Nicolino and Kenwright, Andrew and Wright, Stephen and Calvo, Inmaculada and Cuttica, Ruben and Ravelli, Angelo and Schneider, Rayfel and Woo, Patricia and Wouters, Carine and Xavier, Ricardo and Zemel, Lawrence and Baildam, Eileen and Burgos-Vargas, Ruben and Dolezalova, Pavla and Garay, Stella M and Merino, Rosa and Joos, Rik and Grom, Alexei and Wulffraat, Nico and Zuber, Zbigniew and Zulian, Francesco and Lovell, Daniel and Martini, Alberto}}, issn = {{0028-4793}}, journal = {{NEW ENGLAND JOURNAL OF MEDICINE}}, keywords = {{ETANERCEPT,CHILDREN,INTERLEUKIN-6,DOUBLE-BLIND,CHRONIC INFLAMMATION,PRELIMINARY DEFINITION,RHEUMATOID-ARTHRITIS,RECEPTOR ANTAGONIST ANAKINRA,DISEASE,SAFETY}}, language = {{eng}}, number = {{25}}, pages = {{2385--2395}}, title = {{Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis}}, url = {{http://doi.org/10.1056/NEJMoa1112802}}, volume = {{367}}, year = {{2012}}, }
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