A4: Efficacy and Safety of Tocilizumab in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: 2-Year Data From CHERISH

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) ([1]). 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 (1) 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. Table 1. 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, % Data are mean ± SD, unless stated otherwise. Patients who withdrew because of nonsafety reasons are nonresponders. Patients who withdrew because of safety are included using last observation carried forward. a Patients who withdrew are excluded. b Parent-rated. c No active joints, no active uveitis, ESR <20 mm/h, and physician global assessment VAS ≤10. d Met criteria for inactive disease at each visit for 6 preceding months. JIA ACR70 responders,a n (%) – 65 (79.3) – 71 (86.6) – JIA ACR90 responders,a n (%) – 65 (79.3) – 71 (86.6) – Active joints (0–71) 19.7 ± 14.0 4.7 ± 9.1 −82.4 ± 24.9 3.3 ± 9.1 −87.7 ± 27.1 Joints with limitation of movement (0–67) 16.5 ± 13.8 5.6 ± 10.1 −73.5 ± 30.7 3.6 ± 7.3 −81.3 ± 31.7 Patient globalc (VAS 0–100 mm) 45.5 ± 23.1 12.2 ± 19.0 −62.5 ± 76.3 9.1 ± 18.4 −75.4 ± 43.8 Patient globalb (VAS 0–100 mm) 45.5 ± 23.1 12.2 ± 19.0 −62.5 ± 76.3 9.1 ± 18.4 −75.4 ± 43.8 Physician global (VAS 0–100 mm) 57.8 ± 20.3 8.8 ± 10.9 −85.3 ± 16.8 5.0 ± 10.5 −89.7 ± 23.7 CHAQ-DI (0–3) 1.2 ± 0.7 0.4 ± 0.5 −66.0 ± 44.7 0.2 ± 0.4 −76.7 ± 34.7 ESR (mm/h) 31.7 ± 22.9 5.4 ± 6.3 −76.5 ± 22.0 5.1 ± 5.6 −76.2 ± 27.3 Inactive disease,c n (%) – 33 (40.2) – 52 (63.4) – Remission,d 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) – 48 (58.5) – Conclusion: The efficacy of TCZ was maintained through 2 years of treatment in patients with pcJIA, with no change in safety profile from that reported previously ([1]).