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  • Open Access

Efficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA): TENDER 52-week data

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Pediatric Rheumatology201210 (Suppl 1) :A58

https://doi.org/10.1186/1546-0096-10-S1-A58

  • Published:

Keywords

  • Juvenile Idiopathic Arthritis
  • Pneumothorax
  • Tocilizumab
  • ACR70 Response
  • Physician Global Assessment

Purpose

Treatment options for sJIA are limited. Excessive IL-6 production has been implicated in several manifestations of this disease. In a previous Japanese study, TCZ, an IL-6 receptor inhibitor, improved arthritis and systemic features of patients with refractory sJIA. We present efficacy and safety of TCZ in patients with active sJIA who were treated for ≥52 wks in the global, 3-part, 5-yr, phase 3, multicenter TENDER study.

Methods

Patients (N=112) 2–17 yrs with active sJIA for ≥6 mo and inadequate response to corticosteroids (CS) and NSAIDs were randomized 2:1 to TCZ (8 mg/kg if body weight ≥30 kg; 12 mg/kg if <30 kg) or placebo (control) every 2 wks for 12 wks in part 1; all patients received open-label TCZ at 8 or 12 mg/kg per body weight in part 2. Patients who escaped to open-label TCZ in part 1 also entered part 2. Oral CS tapering was permitted at wks 6 and 8 in part 1 and in the open-label extension in patients with ACR70 response, ESR <20 mm/h, and no fever. Efficacy data are presented for patients who had reached wk 52 of TCZ treatment by May 10, 2010 (n=88); safety data through May 10, 2010 are presented for all patients (n=112). Wk 52 baseline was the first TCZ dose; part 1 placebo patients were re-baselined when they escaped or entered part 2.

Results

Proportions of TCZ patients who achieved JIA ACR30 + absence of fever or JIA ACR70/90 progressively improved from wk 12 to wk 52 (Table). Number (mean±SD) of joints with active arthritis or with limited range of motion decreased from 19.8±15.7 and 19.8±15.6, respectively, at baseline to 3.0±7.0 and 7.5±11.7, respectively, at wk 52, with 45% of patients having 0 active joints. At baseline, 55% of patients (n=62) had fever (temperature ≥37.5°C in the preceding 14 days), while at wk 52 only 9% (n=8) had fever. From baseline to wk 52, improvement in the scores was: CHAQ-DI from 1.7±0.9 to 0.7±0.8; physician global assessment VAS from 64.9±22.3 to 9.7±12.8, and patient/parent global assessment VAS from 58.7±24.4 to 12.6±18.5. There was a marked reduction in CS dose from 0.30±0.20 mg/kg/d at baseline to 0.06±0.08 at wk 52, with 48% having discontinued CS. There were 33 serious AEs (SAEs) in 25 patients; 12 SAEs were considered related (remote, possible, or probable) to TCZ (SAE rate: 0.23/patient year [PY] in part 1, 0.25/PY in part 2). Among the 15 serious infections, 6 were considered related to TCZ; all resolved and none led to study discontinuation. Twelve patients withdrew: 4 because of AEs; 4 because of insufficient response, 3 withdrew consent or did not return, and 1 died of a suspected tension pneumothorax unrelated to treatment.

Table 1

 

Wk 12

Wk 52

 

Control

TCZ

TCZ

JIA ACR responses, n (%)

(N=37)

(N=75)

(N=88)

ACR30 = absence of fever

9 (24)

64 (85)

77 (88)

ACR70

3 (8)

53 (71)

78 (89)

ACR90

2 (5)

28 (37)

57 (65)

Conclusion

Year 1 results from this first global phase 3 study demonstrate that TCZ is highly effective and generally well tolerated in patients with sJIA.

Disclosure

Fabrizio De Benedetti: Bristol-Myers Squibb, 5, Hoffmann-La Roche, Inc., 2, 5, Pfizer Inc, 5; Hermine Brunner: Roche , 5; Nicola Ruperto: None; R. Cuttica: None; Clara Malattia: None; Rayfel Schneider: Roche , 5; Patricia Woo: None; Despina Eleftheriou: None; Eileen Baildam: None; Ruben Burgos-Vargas: Abbott Laboratories, 5, 8, Pfizer Inc, 5, 8, Roche , 5, 8, Schering-Plough, 5, 8, Wyeth Pharmaceuticals, 5, 8; Pavla Dolezalova: None; Stella M. Garay: None; Rik Joos: None; Nico Wulffraat: None; Zbyszek Zuber: None; Francesco Zulian: None; Carine Wouters: None; Ricardo M. Xavier: Merck Pharmaceuticals, 8, Pfizer Inc, 5, 8, Roche , 8; Lawrence Zemel: None; Stephen Wright: Roche , 3; Andy Kenwright: Roche , 3; Alberto Martini: None; Daniel Lovell: Roche Diagnostics , 5.

Authors’ Affiliations

(1)
Alder Hey Children's Foundation NHS Trust, Liverpool, UK
(2)
Charles University in Prague, Prague, Czech Republic
(3)
Children St. Louis Hospital, Strzelecka, Poland
(4)
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
(5)
Cincinnati Children's Medical Center, Cincinnati, OH, USA
(6)
Connecticut Children's Medical Center, Hartford, USA
(7)
Great Ormond Street Children Hospital, London, UK
(8)
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
(9)
Hospital for Sick Children, Toronto, ON, Canada
(10)
Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina
(11)
Hospital General Mexico Univiersidad Nacional Autonoma Mexico, Mexico, Mexico
(12)
Hospital IAEP, La Plata, Buenos Aires, Argentina
(13)
Institute of Child Health, London, UK
(14)
IRCCS G. Gaslini, Genova, Italy
(15)
IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
(16)
Roche, Welwyn, Hertfordshire, UK
(17)
University Hospital Ghent, Ghent, Belgium
(18)
University Hospital Leuven, Leuven, Belgium
(19)
University Medical Center Utrecht, Utrecht, Netherlands
(20)
University of Padua, Padua, Italy

Copyright

© De Benedetti et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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