Background/Purpose: Efficacy and safety of intravenous (IV) tocilizumab (TCZ) were shown in patients (pts) with systemic JIA (sJIA) in the phase 3 TENDER study.¹ This multicenter, open-label, phase 1b study investigated dosing regimens of subcutaneous (SC) TCZ in pts with sJIA relative to data from TENDER to identify the optimal SC regimen and ensure that C_trough from SC regimens was equivalent to or higher than that from the IV regimen.

Methods: Pharmacokinetics (PK), pharmacodynamics (PD), and safety of TCZ SC were investigated in pts aged 1-17 years with sJIA and inadequate response to glucocorticoids; efficacy was an exploratory objective. Pts could be TCZ naive or could switch from TCZ IV to TCZ SC. Interim analysis was conducted after 24 pts had received TCZ SC for 14 weeks. TCZ SC was administered for 52 weeks according to body weight (BW): <30 kg received 162 mg every 10 days (Q10D) before interim analysis or 162 mg every 2 weeks (Q2W) after interim analysis; ≥30 kg received 162 mg every week (QW).

Results: In total, 51 pts were enrolled; 25 weighed <30 kg and 26 weighed ≥30 kg. Twenty-six pts (51%) were TCZ naive and 25 (49%) switched from TCZ IV. Interim analysis revealed higher than desired exposure in the <30 kg group, so dosing frequency was reduced from Q10D to Q2W. Median and range steady state C_min were similar in both BW groups (Table). More than 95% (49/51) of pts treated with TCZ SC had model-computed steady state C_min higher than the 5th percentile achieved with TCZ IV. Median and range AUC_2weeks were similar in both BW groups (Table). Changes in IL-6, CRP, and ESR were similar for both BW groups. Almost all pts had ≥1 adverse event (AE; n = 50; 98.0%). Injection site reactions (ISRs) occurred in 21 pts (41.2%); most were mild, and none led to treatment interruption or withdrawal. The AE rate was 1200.3/100 pt-years (PY) (909.3/100 PY, excluding ISRs). The most common AEs were viral upper respiratory tract infection (13; 25.5%), neutropenia (13; 25.5%), and cough (12; 23.5%). Nine serious AEs occurred in 7 pts (13.7%; 19.3/100 PY); 5 were infections, all in the <30 kg group. Two deaths occurred, both in the <30 kg group. Median Juvenile Arthritis Disease Activity Score-71 improved from baseline to week 52 for TCZ-naive pts (<30 kg, –13.9; ≥30 kg, –12.4) and was maintained or improved further for pts who switched from TCZ IV (<30 kg, –0.7; ≥30 kg –0.2). At week 52, 29/43 pts (67.4%) had inactive disease (JADAS-71 <1.0).

Conclusion: A PK-based strategy was successful in bridging TCZ SC to TCZ IV in pts with sJIA. Dosing regimens of 162 mg Q2W in pts <30 kg and 162 mg QW in pts ≥30 kg provided adequate exposure to support efficacy comparable to that of TCZ IV. Except for ISRs, safety results were consistent with the known safety profile of TCZ in sJIA. Reference: 1. De Benedetti F et al. N Engl J Med. 2012;367:2385-2395. Acknowledgment: The PRINTO and PRCSG Investigators. Medical writing: Sara Duggan, PhD, funded by F. Hoffmann-La Roche Ltd.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-optimal-subcutaneous-doses-of-tocilizumab-in-children-with-systemic-juvenile-idiopathic-arthritis/