Background/Purpose: The US Food and Drug Administration approved intravenous (IV) tocilizumab (TCZ) for patients (pts) ≥2 years of age with systemic JIA (sJIA) in 2011 based on the phase 3 TENDER study.¹ Approval was associated with a postmarketing requirement to investigate TCZ in pts with sJIA <2 years of age (study NP25737; ClinicalTrials.gov, NCT01455701). Results from the 12-week main evaluation period (MEP) have been reported.² Safety results following completion of the optional extension period (OEP) of NP25737 (until 52 weeks from baseline or 2 years of age was reached) are now reported.

Methods: NP25737 was a multicenter, open-label, single-arm study to evaluate pharmacokinetics and safety of IV TCZ 12 mg/kg every 2 weeks for 12 weeks in pts aged <2 years with active sJIA for ≥1 month whose treatment with glucocorticoids and nonsteroidal anti-inflammatory drugs failed and who were receiving stable background therapy. After the MEP, pts could continue TCZ treatment (no requirement for stable background therapy) in the OEP to evaluate long-term safety. Cumulative adverse events (AEs) over the entire study period are reported.

Results: Of 11 pts enrolled in the MEP, 7 entered the OEP and received ≥1 dose of TCZ. For the entire study period (n = 11), the median number of TCZ doses was 11.0 (range, 2-26), and median duration of TCZ exposure was 22.1 weeks (range, 4.1-58.1). Most pts (10/11; 90.9%) had ≥1 AE; most were mild or moderate and unrelated to TCZ. The most common AEs were upper respiratory tract infection (6/11 pts; 54.5%) and hypersensitivity, neutropenia, rash, viral upper respiratory tract infection, and vomiting (each 3/11 pts; 27.3%). Seven serious AEs occurred in 5/11 pts (45.5%): 2 during the OEP (transaminases increased, histiocytosis hematophagic), 3 during the MEP (3 hypersensitivity events), and 2 during safety follow-up of the MEP (sJIA flare, hand-foot-and-mouth disease). AEs leading to dose modification occurred in 5/11 pts (1 in the MEP, 4 in the OEP) mostly because of infections, neutropenia, and elevated liver enzymes, all mild or moderate in intensity. AEs leading to withdrawal occurred in 5/11 pts (45.5%): during the OEP, 1 pt withdrew because of a serious AE of increased transaminases; during the MEP, 3 pts withdrew because of serious hypersensitivity reactions to TCZ and 1 because of thrombocytopenia. No deaths were reported. AE rates are shown in Table 1.

Conclusion: During the OEP, long-term treatment with TCZ was well tolerated in sJIA pts aged <2 years. No additional safety signals were reported in the OEP beyond those reported in the MEP or observed previously for pts with sJIA aged >2 years. References: 1. De Benedetti F et al. N Engl J Med. 2012;367:2385-2395. 2. Mallalieu NL et al. Arthritis Rheumatol. 2017;69(suppl 10):abstract 2856. Medical writing: Sara Duggan, PhD, funded by F. Hoffmann-La Roche Ltd. Acknowledgment: Dave Mathis, Leanne Wilson.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-tocilizumab-in-patients-aged/