Background The introduction of biologic drugs has substantially changed the treatment of children with a severe course of juvenile idiopathic arthrits (JIA). Etanercept (ETA) has been the most frequently used biologic drug in patients with JIA followed by Adalimumab (ADA). However, published data on the long-term safety of biologic drugs are limited (i) by a small number of years under drug exposure in recent studies and (ii) the lack of a biologic naive control group.
Objectives To investigate the exposure-adjusted rates of serious adverse events (SAEs) and of events of special interest (ESIs) in order to evaluate the long-term safety of ETA and ADA compared to methotrexate (MTX).
Methods Patients with polyarticular JIA who were prospectively observed in the national JIA biologic register BiKer and the adult JIA register JuMBO were considered for this analysis. All adverse events recorded by physicians over the whole observation period were categorized on the basis of MedDRA. Total exposure-adjusted rates (EY) for SAEs and ESIs were calculated. An event was attributed to ETA, ADA or MTX when the treatment was either ongoing or terminated in less than 3 month prior to the event. Propensity score methods were applied to model the likelihood of being treated with ETA or ADA instead of MTX. Adjusted relative risks were computed for these subgroups by means of a Poisson regression.
Results A total of 2,263 patients (68% females, ETA start: 1162, ADA start: 46, MTX start: 1055) with polyarticular JIA were included into the safety analyses. Of these, 1,414 patients were ever treated with ETA (4,500 years of exposure), 320 patients with ADA (500 years of exposure) and 1,455 with MTX without a biologic DMARD (2,900 years of exposure). At the start with ETA or ADA, 78% of the patients also received MTX. The exposure-adjusted rates for SAE and ESIs, are given in the table. Three deaths occurred (0.05/100 EY) in patients who were ever treated with ETA in their disease course and one (0.04/100 EY) died in the MTX control group. The rates of malignancies between patients ever exposed to ETA or ADA compared to MTX did not significantly differ (MTX: 2, 0.07 events/100 EY, ETA: 5, 0.08 events/100 EY, ADA: 1, 0.14 events/100 EY).
Conclusions This is the most comprehensive study of the long-term safety of Eta and Ada. It confirms the good tolerability of the substances reported in other studies. However, even in this large cohort the number of events is still too small to reliably estimate the risk of single events of interest.
Disclosure of Interest J. Klotsche: None declared, M. Niewerth: None declared, E. Seipelt: None declared, G. Horneff Grant/research support: Joint unconditional grant from Pfizer, Abbvie and Roche, K. Minden Grant/research support: Joint unconditional grant from Pfizer and Abbvie