Interleukin-23 in early disease development in rheumatoid arthritis

Abstract

Objectives: To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis (eRA) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels.

Method: Treatment-naïve eRA patients from the OPERA cohort were included (n = 151). Patients were randomized to methotrexate (MTX) plus adalimumab (ADA; n = 75) or MTX plus placebo-ADA (PLA; n = 76). Plasma samples were obtained at baseline and at months 3, 6, and 12 together with values for C-reactive protein (CRP), the 28-joint Disease Activity Score based on CRP (DAS28CRP), scores on the Clinical Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI), visual analogue scale (VAS) for pain/fatigue/physician global and total Sharp/van der Heijde score (TSS). IL-23 was measured at each time point.

Results: IL-23 levels decreased significantly in the ADA group from 20.6 pg/mL (IQR 13.1–32.7 pg/mL) at baseline to 18 pg/mL (IQR 7.2–25.0 pg/mL) at 12 months (p < 0.01). No significant decrease in IL-23 level was observed in the PLA group. No associations between baseline IL-23 levels and measures of disease activity (DAS28CRP, CRP, CDAI, or SDAI) at 12 or 24 months were present in the treatment groups. Baseline IL-23 correlated inversely with changes in TSS and symptom duration before diagnosis.

Conclusions: Our data show increased baseline levels and a significant decrease in IL-23 levels in eRA patients treated with anti-TNF-α. The inverse correlation with duration of symptoms before diagnosis supports the importance of IL-23 in the preclinical disease development of RA.

Acknowledgements

The study was supported by an unrestricted grant from Janssen Cilag. The OPERA trial was supported by grants from Abbott Laboratories, Denmark, who also provided free study medication (adalimumab and placebo-adalimumab). Triamcinolone was supplied by Meda Pharmaceuticals, Denmark. Janssen, Abbott and Meda were not involved in the study set-up, data collection, analysis, or interpretation, and had no influence on the publication of the data.