Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Tocilizumab Is Efficacious in Patients with Systemic Juvenile Idiopathic Arthritis Across Baseline Demographic and Disease Characteristics and Prior/Baseline Treatments: 52-Week Data From a Phase 3 Clinical Trial.

De Benedetti1,  Fabrizio, Brunner2,  Hermine, Allen3,  Roger, Brown2,  Diane, Chaitow3,  Jeffrey, Pardeo3,  Manuela, Espada3,  Graciela

Ospedale Pediatrico Bambino Gesù, Rome, Italy
Pediatric Rheumatology Collaborative Study Group [PRCSG], Cincinnati, OH
Paediatric Rheumatology International Trials Organisation—IRCCS [PRINTO], Genova, Italy
Roche, Welwyn, United Kingdom
University College London Medical School, London, United Kingdom

Background/Purpose:

A placebo-controlled phase 3 trial (TENDER) demonstrated that the interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) is effective in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA). The aim of this analysis was to examine whether baseline characteristics of patients with sJIA were associated with the long-term response to TCZ during the open-label (OL) extension of the TENDER trial.

Methods:

Patients aged 2–17 years with active sJIA (>=6 months; inadequate response to prior nonsteroidal anti-inflammatory drugs [NSAIDs] and oral corticosteroids [CS]) who received TCZ or placebo every 2 weeks for 12 weeks in the placebo-controlled portion of the study (part 1) went on to receive OL TCZ in part 2 (extension) of the study. Stable doses of NSAIDs and methotrexate (MTX) were continued, with oral CS tapering permitted according to predefined criteria based on JIA ACR response, absence of fever, and erythrocyte sedimentation rate in part 1 and part 2. In part 1, patients qualifying for rescue therapy received standard of care and were offered OL TCZ. This post hoc analysis examines the proportion of patients with JIA ACR30 response plus absence of fever and JIA ACR70 response at week 52 by baseline demographic and disease characteristics and prior/baseline treatments. Baseline for analyses was first dose of TCZ. Patients who withdrew due to insufficient therapeutic response (n=2) before week 52 were included and considered nonresponders, and patients who withdrew for non–efficacy-related reasons (safety, n=4; other, n=2) before week 52 were excluded.

Results:

The intent-to-treat (ITT) population consisted of 112 patients (37 randomized to placebo and 75 randomized to TCZ in part 1). At the longer-term extension data cut, 103 patients had reached week 52 or previously withdrew due to insufficient therapeutic response. In each of the evaluated subgroups, the majority of patients achieved JIA ACR30 response plus absence of fever and/or JIA ACR70 response at week 52 (Table). No substantial differences in response were observed in patients grouped by baseline characteristics, including age, region, disease duration, number of active joints, fever status, C-reactive protein (CRP) level, oral CS dose, MTX use, and previous biologic treatment (IL-1 or TNF-a inhibitor).

Table. Efficacy End Points with TCZ Treatment at Week 52 by Selected Baseline Characteristics (ITT Population)

 n at baselineJIA ACR30 Response + Fever Absenta at Week 52, % (r/n)JIA ACR70 Response at Week 52, % (r/n)
Age, y   
  2–52788.5 (23/26)88.5 (23/26)
  6–124888.1 (37/42)88.1 (37/42)
  13–173785.7 (30/35)85.7 (30/35)
Region   
  Europe6183.6(46/55)85.5 (47/55)
  North America2486.4 (19/22)86.4 (19/22)
  South America22100 (21/21)95.2 (20/21)
  Other580.0 (4/5)80.0 (4/5)
CRP Level, mg/L   
  <503192.9 (26/28)85.7 (24/28)
  >=508185.3 (64/75)88.0 (66/75)
Disease Duration, y   
  <45680.8 (42/52)90.4 (47/52)
  >=45694.1 (48/51)84.3 (43/51)
Active Joints, n   
  0–93590.3 (28/31)90.3 (28/31)
  10–295582.4 (42/51)88.2 (45/51)
  30–712295.2 (20/21)81.0 (17/21)
Fever Freeb   
  Yes5091.3 (42/46)82.6 (38/46)
  No6284.2 (48/57)91.2 (52/57)
Oral CS Dose, mg/kg/dc   
  <0.35586.0 (43/50)84.0 (42/50)
  >=0.35788.7 (47/53)90.6 (48/53)
Background MTX Use   
  Yes7889.0 (65/73)90.4 (66/73)
  No3483.3 (25/30)80.0 (24/30)
Previous Biologic Treatment   
  Yes9288.0 (73/83)85.5 (71/83)
  No2085.0 (17/20)95.0 (19/20)
Previous IL-1 Inhibitor Treatment   
  Yes5487.5 (42/48)83.3 (40/48)
  No5887.3 (48/55)90.9 (50/55)
a Fever present, defined as any temperature >=37.5°C in the 7 days preceding the week 52 visit.
b Fever present, defined as a temperature of >=37.5°C in the 14 days preceding the baseline visit.
c Prednisone equivalent.
r/n=no. of responders/no. of patients reaching week 52 visit + no. of patients who previously withdrew due to insufficient therapeutic response.

Conclusion:

TCZ was effective and provided a sustained response in patients with sJIA at 52 weeks across multiple baseline characteristics, including longer disease duration, highly active and severe disease, and previous treatment with biologic therapy.

To cite this abstract, please use the following information:
De Benedetti, Fabrizio, Brunner, Hermine, Allen, Roger, Brown, Diane, Chaitow, Jeffrey, Pardeo, Manuela, et al; Tocilizumab Is Efficacious in Patients with Systemic Juvenile Idiopathic Arthritis Across Baseline Demographic and Disease Characteristics and Prior/Baseline Treatments: 52-Week Data From a Phase 3 Clinical Trial. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2621
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