Background/Purpose: The efficacy and safety of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor-alpha inhibitor, have been demonstrated in patients (pts) with polyarticular-course juvenile idiopathic arthritis (pcJIA) (Brunner HI et al. Ann Rheum Dis. 2014;74:1110-7). This study investigated appropriate dosing regimens of subcutaneous (SC) TCZ in pts with pcJIA.

Methods: We enrolled pts aged 1-17 years with pcJIA and previous inadequate response/intolerance to methotrexate who were TCZ naive or were receiving TCZ IV with adequate disease control. TCZ SC was administered open label according to a body weight (BW)–based dosing regimen designed following PK simulations of the approved IV dosing in pcJIA and SC dosing in adult rheumatoid arthritis: pcJIA pts weighing <30 kg received TCZ 162 mg every 3 weeks (Q3W) and pcJIA pts weighing ≥30 kg received TCZ 162 mg Q2W for 52 weeks. Model-computed pharmacokinetic (PK) and pharmacodynamic (PD) parameters and safety and efficacy (exploratory) were assessed.

Results: Fifty-two pts were enrolled; 27 <30 kg BW received TCZ 162 mg SC Q3W and 25 ≥30 kg BW received TCZ 162 mg SC Q2W. Overall, 69% of pts were female. Median baseline age was 6.0 years for the <30 kg BW group and 15.0 years for the ≥30 kg BW group; 85% and 56%, respectively, were TCZ naive. Because no notable differences in steady state PK occurred between naive vs non-naive pts, pooled data are presented. Median C_min was similar between BW groups and higher than previously established with TCZ IV (TCZ IV median C_min: 3.2 μg/mL for TCZ 10 mg/kg <30 kg BW and 7.3 μg/mL for TCZ 8 mg/kg ≥30 kg BW), ensuring adequate exposure from SC doses. Median C_max from SC dosing was lower than from IV dosing in both BW groups (TCZ IV median C_max: 191 μg/mL for TCZ 10 mg/kg <30 kg BW and 201 μg/mL for TCZ 8 mg/kg ≥30 kg BW). C_max and AUC_12weeks were higher with TCZ SC in the <30 kg BW group than the ≥30 kg BW. Changes in PD parameters for TCZ-naive pts were consistent with those previously observed for TCZ IV and suggest improvement of inflammation. JADAS-71 generally improved in both BW groups (Table), with trends consistent with those observed for TCZ IV. Infections were the most frequent adverse event (AE), reported in 20 pts in the <30 kg BW group and 16 pts in the ≥30 kg BW group (Table). Injection site reactions were more common in the ≥30 kg BW group (Table). The most common symptoms were erythema, swelling, hematoma, pain, and pruritus. No serious hypersensitivity, AE leading to withdrawal, opportunistic infection, serious hepatic AE, or death occurred. There were 2 serious AEs (croup and varicella) in 1 pt in the <30 kg group and 2 serious AEs (anorexia and arthralgia) in 2 pts in the ≥30 kg group; the overall rate was 7.9/100 pt-years, consistent with that for TCZ IV.

Conclusion: The BW-based TCZ SC dosing regimens for pcJIA provided adequate exposure to support efficacy comparable to that of TCZ IV, with an acceptable benefit-risk profile.