Background/Purpose: Elevated IL-6 levels are associated with disease activity in patients (pts) with juvenile idiopathic arthritis (JIA).¹ Tocilizumab (TCZ), an IL-6 receptor inhibitor, was evaluated for the treatment of polyarticular-course JIA (pcJIA; RF+ and RF– poly- and extended oligoarticular JIA; systemic JIA was excluded) in the CHERISH study.

Methods: CHERISH is a 104-wk study in pts age 2-17 yrs with active pcJIA for ≥6 mo who failed MTX. In the first 16 wks, all pts received open-label (OL) TCZ every 4 wks (if body weight [BW] ≥30 kg, 8 mg/kg [n = 119]; if BW <30 kg, pts were randomly assigned to 8 mg/kg [n = 34] or 10 mg/kg [n = 35]). At wk 16, eligible pts (with ≥JIA ACR30 response) entered a 24-wk randomized (pts were assigned [1:1] to placebo [PBO] or to continue TCZ at the same dose), double-blind (DB) withdrawal period for evaluation of the primary endpoint (JIA ACR30 flare relative to wk 16). Pts who flared or completed the DB period entered an OL extension in which they received the same TCZ dose as in the lead-in period. Efficacy data (until wk 40) are presented for the ITT population; safety data are presented for the safety population to the cut date.

Results: 188 pts entered the initial lead-in period (77% girls; 79% and 46% were receiving concurrent MTX and oral corticosteroids [CS], respectively); 166 pts entered the DB period; 15 pts (8%) withdrew due to insufficient response, 3 (2%) due to adverse events (AEs), and 4 (2%) due to other reasons. The primary endpoint was met, and JIA ACR30/50/70 responses were significantly higher with TCZ compared to PBO at wk 40 (Table). Efficacy responses for the initial lead-in period at wk 16 are shown (Table). The degree of improvement was lower for these endpoints in the TCZ 8 mg/kg <30 kg BW group compared with the other 2 groups (TCZ 10 mg/kg <30 kg BW and TCZ 8 mg/kg ≥30 kg BW) (Table). At the time of the safety data cut, there were 184 pt-yrs (PY) of follow-up in the 188 pts enrolled. Rates/100PY of AEs and SAEs were 480 and 12.5; infections were the most common AEs (164/100PY) and SAEs (4.9/100PY). ALT and AST elevations ≥3× ULN were each reported in 3.7% and <1% of pts. Neutropenia (<1000 cells/mm³) and thrombocytopenia (<50,000 cells/mm³) occurred in 3.7% and 1.1% of pts. LDL-cholesterol ≥110 mg/dL occurred in 11.4% of pts. No grade 3/4 (>3 ULN) elevations of serum bilirubin were reported.

Conclusion: TCZ treatment in pcJIA was efficacious, with a sustained clinically meaningful improvement using a monthly regimen at doses of 8 mg/kg if BW ≥30 kg and 10 mg/kg if BW <30 kg. The safety profile is consistent with that in other TCZ-treated pts (eg, systemic JIA).²

References

1. De Benedetti Clin Exp Rheumatol. 1992;493. 2. De Benedetti Ann Rheum Dis 2011;70(suppl 3):67.