Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Tocilizumab in Patients with Systemic Juvenile Idiopathic Arthritis: Efficacy Data from the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Trial.

De Benedetti1,  Fabrizio, Brunner4,  Hermine, Ruperto9,  Nicola, Calvo5,  Inmaculada, Cuttica10,  Ruben, Malattia11,  Clara, Schneider2,  Rayfel

IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy
PRINTO, Buenos Aires, Argentina
PRINTO
Roche, Welwyn, UK, Welwyn, United Kingdom
PRCSG, Toronto, ON, Canada
PRCSG, Hartford, CT
PRCSG, Cincinnati, OH
PRINTO, Valencia, Spain
PRINTO, Porto Alegre, Brazil
PRINTO, London, United Kingdom
PRINTO, Leuven, Belgium
PRINTO, Genova, Italy

Purpose:

Systemic juvenile idiopathic arthritis (sJIA) is the most severe form of JIA and is characterized by arthritis and prominent systemic manifestations. Interleukin-6 (IL-6) plays a pivotal role in sJIA pathogenesis. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, was shown to be effective in a Japanese phase 3, placebo-controlled, withdrawal-design trial in patients with sJIA. We report 12-week efficacy data from the global phase 3 TENDER trial in patients with sJIA.

Methods:

Patients with active sJIA (age range, 2–17 years; disease duration, >=6 months; inadequate response to previous NSAIDs and corticosteroids) were randomly assigned 2:1 to receive TCZ every 2 weeks (8 mg/kg for patients >=30 kg body weight; 12 mg/kg for patients <30 kg) or placebo (control). Stable doses of NSAIDs and methotrexate were continued, and corticosteroid tapering was allowed from week 6. Patients who qualified for rescue therapy received standard of care, were offered open-label TCZ, and were considered nonresponders. Primary end point was the proportion of patients with JIA ACR30 response plus absence of fever at week 12 (ITT analysis).

Results:

The ITT population consisted of 112 patients (37 controls, 75 TCZ). Baseline characteristics were similar between groups. By week 12, 3% of patients in both arms (1 control, 2 TCZ) withdrew from the study, and more control than TCZ patients required rescue therapy (54% vs 3%). Significantly more TCZ patients experienced JIA ACR30 response plus absence of fever at week 12 compared with controls (85% vs 24%; p<0.0001). Additionally, significantly more TCZ patients than controls achieved JIA ACR50/70/90 response (Table A). Of the patients who had fever at baseline, significantly more TCZ patients than controls had no fever at week 12. Similarly, of those patients with anemia or thrombocytosis at baseline, significantly more patients treated with TCZ than control had normal hemoglobin levels or normal platelet counts, respectively (Table A). A considerable proportion of TCZ patients achieved ACR70/90 responses, even in subgroups whose baseline characteristics included a high number of active joints, fever, or a high platelet count, and in those treated with prior biologic therapy (Table B). Four serious adverse events were reported in 3 TCZ patients—angioedema and urticaria (1), varicella (1), and bacterial arthritis (1)—all of which resolved without sequelae.

Conclusions:

These results show that TCZ is highly effective in treating sJIA, as shown by the clinically relevant JIA ACR70 and ACR90 responses, irrespective of baseline characteristics such as active joint disease, fever, high platelet count, and previous biologic therapy.

Table A. Efficacy Outcomes at Week 12

 Control, n = 37TCZ, n = 75
JIA ACR50 responses, n (%)4 (11)64 (85)a
JIA ACR70 responses, n (%)3 (8)53 (71)a
JIA ACR90 responses, n (%)2 (5)28 (37)a
No fever after having a fever at baseline, n/n (%)5/24 (21)35/41 (85)a
Normal hemoglobin after having anemia at baseline, n/n (%)2/29 (7)40/50 (80)a
Normal platelet count after having thrombocytosis at baseline, n/n (%)1/26 (4)47/52 (90)a

Table B. Efficacy Outcomes at Week 12 by Select Baseline Characteristics, n/n (%)

  TCZ, n = 75
  ACR 30 + absence of feverACR70ACR90
No. of active joints0–918/20 (90)13/20 (65)7/20 (35)
 10–2932/39 (82)30/39 (77)18/39 (46)
 30–7114/16 (88)10/16 (63)3/16 (19)
Fever status (last 7 d)Fever present27/32 (84)24/32 (75)11/32 (34)
 Fever free37/43 (86)29/43 (67)17/43 (40)
Platelet countb<=ULN13/20 (65)11/20 (55)9/20 (45)
 > ULN48/52 (92)39/52 (75)18/52 (35)
Previous anakinra useYes35/41 (85)29/41 (71)16/41 (39)
 No29/34 (85)24/34 (71)12/34 (35)
Previous TNF-a inhibitor useYes45/55 (82)35/55 (64)19/55 (35)
 No19/20 (95)18/20 (90)9/20 (45)
TNF = tumor necrosis factor.
ITT analysis; analysis adjusted for randomization stratification factors applied at baseline.
*p < 0.0001.
b Data missing for 3 patients.

To cite this abstract, please use the following information:
De Benedetti, Fabrizio, Brunner, Hermine, Ruperto, Nicola, Calvo, Inmaculada, Cuttica, Ruben, Malattia, Clara, et al; Tocilizumab in Patients with Systemic Juvenile Idiopathic Arthritis: Efficacy Data from the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1434
DOI: 10.1002/art.29200

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