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

Abstract

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...

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

“…d n calculated by reviewer (155 completed 104 weeks; 82 TCZ group completed 104 weeks). e Two abstracts 69,74 contain a table with a footnote to indicate patients who withdrew were excluded; however, in the third abstract 71 the table footnote states that patients who withdrew owing to non-safety reasons are non-responders, whereas patients who withdrew owing to safety are included using LOCF. f No active joints, no active uveitis, ESR < 20 mm/hour and PGA VAS ≤ 10.…”

“…69 The equivalent SAEs rate was 11.1 per 100 patient-years (Table 24). Infections categorised into the most common AEs and SAEs were 151.4 and 5.2 per 100 patient-years, respectively.…”

“…Studies included (n = 4) (described by 9 full papers and 12 conference abstracts) [65][66][67] ) and one RCT evaluated tocilizumab [68][69][70][71][72][73][74][75][76] (the CHERISH trial). For the sake of brevity, generally only the key reference for each RCT is cited in the main text of this report.…”

“…69,71,74 Only participants who achieved at least ACR Pedi-30 during the open-label phase and who then continued into the double-blind RCT phase of the trial were eligible to enter the OLE, either after a JIA flare or when they completed the double-blind RCT phase. One-hundred and sixty (96%) of the 166 participants eligible to enter the OLE did so and 155 (97%) completed 104 weeks of follow-up (16-week open-label plus 24 weeks double-blind RCT plus 64 weeks OLE).…”

“…One of the studies is a RCT comparing tocilizumab with placebo (CHERISH) 68 linked to six additional conference publications/abstracts. 69,[71][72][73]76,100 The CHERISH RCT 68 met the inclusion criteria of this assessment report and was reported above in Results. Of the six conference publications/abstracts linked to the CHERISH RCT, only two were related to the randomised phase of the trial 72,73 and the remaining four were related to the OLE phase.…”