THU0598 Safety of tocilizumab in patients aged &lt;2 years with active systemic juvenile idiopathic arthritis treated for one year
Authors: S. Wimalasundera, I. Calvo Penades, R. Cuttica, H.-I. Huppertz, R. Joos, D. Milojevic, M. Rosenkranz, K. Schikler, T. Constantin, W. Douglass, C. Wells, Y. Kimura, C. Wouters
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Intravenous (IV) tocilizumab (TCZ) was approved in the, US (2011), EU (2013) and other countries for the treatment of systemic juvenile idiopathic arthritis (sJIA) patients (pts)≥2 years of age, based on a phase 3 study WA18221.<sup>1</sup> US Food and Drug Administration approval resulted in postmarketing requirement to investigate TCZ in pts with sJIA &lt;2 years of age (study NP25737; ClinicalTrials.gov, NCT01455701). Results from the 12 week main evaluation period (MEP) have been reported.<sup>2</sup> <h3>Objectives</h3> Report safety results after completion of the optional extension period (OEP) of NP25737 (until 52 weeks from baseline or 2 years of age, whichever was longer). <h3>Methods</h3> NP25737 was a multicenter, open-label, single-arm study to evaluate the pharmacokinetics and safety of IV TCZ, 12 mg/kg every 2 weeks, for 12 weeks in pts aged &lt;2 years with active sJIA for ≥1 month who failed corticosteroid and nonsteroidal anti-inflammatory drug treatment and received stable background therapy during the MEP. After the 12 week MEP, pts could participate in the OEP and continue TCZ treatment (without requirement for stable background therapy). Cumulative adverse events (AEs) over the entire study period are reported. <h3>Results</h3> Seven of 11 pts enrolled in the MEP continued to the OEP and received ≥1 dose of TCZ. Over the entire study period (n=11), the median number of TCZ doses was 11 (range, 2–26) and the median duration of TCZ exposure was 22 weeks (range, 4–58). Most pts (10/11; 91%) had ≥1 AE; most were mild or moderate in intensity and unrelated to study drug. The most common AEs were upper respiratory tract infection (6/11 pts, 55%), hypersensitivity, neutropenia, rash, viral upper respiratory tract infection, and vomiting (each in 3/11 pts; 27%). Seven serious AEs occurred in 5 of 11 pts (46%): 2 in the OEP (transaminases increased and histiocytosis hematophagic), 3 in the MEP (3 hypersensitivity events), and 2 in the safety follow-up of the MEP (sJIA flare and hand-foot-and-mouth disease). AEs leading to dose modification occurred in 5 of 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 of 11 pts (46%): 1 in the OEP because of serious increased transaminases, 3 in the MEP because of serious hypersensitivity reactions to TCZ, and 1 in the MEP because of thrombocytopenia. No deaths were reported during the study. AE rates per 100 pt-years of exposure are reported in the table 1. <h3>Conclusions</h3> During the OEP of the study, long-term treatment with TCZ was well tolerated in sJIA pts aged &lt;2 years, and 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. <h3>References</h3> [1] De Benedetti F, et al. N Engl J Med2012;367:2385–2395. [2] Mallalieu NL, et al. Arthritis Rheumatol2017;69(suppl 10):abstract 2856. <h3>Acknowledgements</h3> This study was sponsored by F. Hoffmann-La Roche Ltd. <h3>Disclosure of Interest</h3> S. Wimalasundera Employee of: Roche, I. Calvo Penades: None declared, R. Cuttica Consultant for: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, Speakers bureau: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, H.-I. Huppertz: None declared, R. Joos: None declared, D. Milojevic: None declared, M. Rosenkranz: None declared, K. Schikler: None declared, T. Constantin: None declared, W. Douglass Employee of: Roche, C. Wells Shareholder of: Roche, Employee of: Roche, Y. Kimura Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, C. Wouters: None declared