ObjectiveTo evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).MethodsThis three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab.ResultsIn part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY).ConclusionsTocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis.Trial registration number:NCT00988221.

Background/Purpose: The efficacy and safety of tocilizumab (TCZ), an interleukin‐6 receptor inhibitor, were previously demonstrated at week 40 of CHERISH, a phase 3 trial in patients with polyarticular‐course juvenile idiopathic arthritis (pcJIA) (). Here we report the efficacy and safety of TCZ over 104 weeks of treatment in patients with pcJIA. Methods: Patients 2 to 17 years old with ≥6 months' active pcJIA who failed methotrexate received open‐label TCZ (weight ≥30 kg, 8 mg/kg [n = 119]; weight ≥30 kg, randomly assigned [1:1] to 8 [n = 34] or 10 [n = 35] mg/kg) every 4 weeks for 16 weeks. Patients with ≥JIA American College of Rheumatology (ACR) 30 response at week 16 entered a 24‐week, double‐blind withdrawal period and were randomly assigned (1:1) to placebo or continuation with TCZ. Patients with JIA ACR30 flare or who completed the withdrawal period entered an open‐label extension through week 104. Results: One hundred eighty‐eight patients entered the lead‐in period, 166 entered the withdrawal period, 160 entered the open‐label extension period, and 155 completed 104 weeks. In patients who received continuous TCZ throughout the study (n = 82), JIA ACR responses, improvement in JIA ACR core components, and proportions of patients with inactive disease or remission () were maintained through week 104. JADAS‐71 scores were maintained through week 104 (Figure); 73% of patients had JADAS‐71 <3.8 (minimal disease activity cutoff), 56% had JADAS‐71 <1 (inactive disease cutoff). The safety population comprised 188 patients with 307 patient‐years (PY). Rates/100 PY of adverse events (AEs) and serious AEs (SAEs) were 406.5 and 11.1, respectively; infections were the most common AE (151.4) and SAE (5.2). ALT and AST elevations ≥3× upper limit of normal occurred in 6.4% and 2.7% of patients, respectively. Grade 3 lowest neutrophil count and grade 2/3/4 thrombocytopenia occurred in 5.9% and 1.6% of patients, respectively. LDL cholesterol ≥110 mg/dL occurred in 16.2% of patients. Efficacy End Points and Percentage Change From Baseline in JIA ACR Componentsa (continuous TCZ, n = 82) Baseline Week 40 Change from baseline to week 40, % Week 104 Change from baseline to week 104, % JIA ACR70 responders, n (%)–65 (79.3)–71 (86.6)–JIA ACR90 responders, n (%)–65 (79.3)–71 (86.6)–Active joints (0–71)19.7 ± 14.04.7 ± 9.1−82.4 ± 24.93.3 ± 9.1−87.7 ± 27.1Joints with limitation of movement (0–67)16.5 ± 13.85.6 ± 10.1−73.5 ± 30.73.6 ± 7.3−81.3 ± 31.7Patient globalc (VAS 0–100 mm)45.5 ± 23.112.2 ± 19.0−62.5 ± 76.39.1 ± 18.4−75.4 ± 43.8Patient global (VAS 0–100 mm)45.5 ± 23.112.2 ± 19.0−62.5 ± 76.39.1 ± 18.4−75.4 ± 43.8Physician global (VAS 0–100 mm)57.8 ± 20.38.8 ± 10.9−85.3 ± 16.85.0 ± 10.5−89.7 ± 23.7CHAQ‐DI (0–3)1.2 ± 0.70.4 ± 0.5−66.0 ± 44.70.2 ± 0.4−76.7 ± 34.7ESR (mm/h)31.7 ± 22.95.4 ± 6.3−76.5 ± 22.05.1 ± 5.6−76.2 ± 27.3Inactive disease, n (%)–33 (40.2)–52 (63.4)–Remission, n (%)–5 (6.1)–31 (37.8)–Minimal disease activity (JADAS‐71 <3.8), n (%)0 (0)49 (59.8)–60 (73.2)–Inactive disease (JADAS‐71 <1), n (%)0 (0)24 (29.3)–4...

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