Op0009 Tocilizumab Versus Tumour Necrosis Factor Inhibition in Polyarticular Juvenile Idiopathic Arthritis 36 Months Data on Effectiveness and Safety From a Comparative Study of the Biker Registry

Background: Tocilizumab (TCZ) has been approved for the treatment of polyarticular juvenile idiopathic arthritis (JIA) since 2013. Data on efficacy and tolerability/safety in long-term treatment are scarce. Objectives: To investigate the tolerability/safety of TCZ compared to tumour necrosis factor inhibitors (TNFi) over 36 months, and to analyse the comparative effectiveness of the substances in patients with first and second-line therapies, respectively. Methods: BIKER WA 29358 is a 5-year multi-centre prospective, observational cohort study including patients with polyarticular JIA in Germany starting treatment between 2015 and 2020 with TCZ and matched patients starting an approved TNFi (etanercept, adalimumab or golimumab). Outcomes included JADAS-10-based inactive disease and low disease activity at 12, 24 and 36 months, rates of adverse events (AE) and drug adherence, which were compared between cohorts. Results: Recruitment of 342 participants (TCZ, n=171; TNFi, n=171) was completed over 3 years ago. TCZ was used as 2nd line biologic in the majority of patients (84%), while TNFi were mostly 1st line biologics (86%). Therefore, patients starting on TCZ were older and had a longer disease duration compared to TNFi patients at treatment initiation. At baseline, significantly more patients received TCZ intravenously (72.5%) than subcutaneously (27.5%); this changed over the course of the study (intravenous 43%/subcutaneous 57%). Proportions of patients in TCZ/TNFi treatment groups achieving JADAS inactive disease at 36 months were 86/45% in 1st line biologic users and 57/50% in 2nd line biologic users, in patients still receiving treatment (PPP). At least JADAS low disease activity (LDA) was achieved in 100/68% in 1st line and 77/88% in 2nd line users of TCZ/TNFi (PPP). No significant difference between subcutaneous and intravenous administration was observed regarding rates of patients reaching JADAS inactive disease and JADAS low disease activity (PPP). Safety was assessed based on AE reporting (Table 1): 93 (54%) patients in the TCZ cohort and 102 (60%) patients in the TNFi cohort reported AE during treatment and up to 90 days after treatment discontinuation. The AE rate was similar in both cohorts (65 vs. 57/100 patient years (PY), RR 1.1 (95%CI 0.9-1.4), Wald-test), but rate of serious AE was higher in the TCZ cohort (3.4 vs. 0.5/100 PY; RR 6.4 (95%CI 1.4-29). No opportunistic infection was reported. Cytopenia was more common in the TCZ cohort (13 vs. 1, RR 15.2 (95%CI 2.0-116.3), uveitis and injection site reactions were more common in the TNFi cohort (3 vs. 13/100PY; RR 0.3 (95%CI 0.08-0.95) and 5 vs. 14/100 PY, RR 0.4 (95%CI 0.2-1.2). There was no case of death or malignancy in patients ever exposed to TCZ or TNFi in this cohort. One pregnancy occurred in the TCZ cohort in the follow-up post 90 days after discontinuation of TCZ, with delivery of a healthy child. Two pregnancies were documented in the control cohort: Outcome was delivery of a healthy child in one case and induced abortion in the other. In the TCZ or TNFi cohorts, 92 (54%) vs. 107 (63%) patients discontinued treatment, 49/38 due to lack of efficacy, 27/42 due to remission and 10/11 due to intolerance, respectively. Conclusion: In this interim analysis, treatment targets were reached with similar frequency after 36 months of treatment with TCZ or TNFi. TCZ was used predominantly as 2nd line biologic. Higher rates of remission and minimal disease activity were observed in 1st line compared to 2nd line biologic users. More serious adverse events were reported in the TCZ cohort. No new safety signals were noted so far. Observation is ongoing. Table 1. Patient characteristics, selected reported adverse events (number and rate). REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Ariane Klein: None declared, Angela Zimmer: None declared, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Christiane Reiser speaker honoraria from Novartis and Galapagos., Advisory boards: Pfzer, Sobi, Jasmin B. Kuemmerle-Deschner Novartis and Sobi, Novartis and Sobi, Novartis and Sobi, Maria Fasshauer: None declared, Kirsten Minden: None declared, Ivan Foeldvari: None declared, Christoph Rietschel: None declared, Daniel Windschall Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell Novartis, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prassad Thomas Oommen: None declared, Frank Dressler: None declared, Gerd Horneff MSD, Roche, Pfizer, MSD, Roche, Pfizer.