Background/Purpose: Interleukin-20 (IL-20) is a pro-inflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Clinical phase 2a testing has shown that treatment with an anti-IL-20 monoclonal antibody (NNC0109-0012) reduces disease activity in patients with RA. In order to further explore the role of IL-20 in arthritis pathogenesis we have investigated the effects of a neutralizing anti-IL-20 antibody in the collagen induced arthritis (CIA) model.

Methods: Two separate experiments in the mouse CIA model were conducted to test the effect of an anti-IL-20 antibody (5B7, human IgG4), which cross reacts with mouse IL-20. Two doses of 5B7 (1 and 10 mg/kg, 3xweek for 6 weeks) were tested in a prophylactic setting with dosing from day 0 after immunization. Three doses of 5B7 (1, 10, and 40 mg/kg, 3xweek for 3 weeks) were tested in a late prophylactic setting with dosing from day 21. Serum samples were collected for exposure analysis and to test for anti-drug antibodies and anti-collagen type II (CII) antibody levels. Paws were collected for histopathological evaluation. Overall mRNA expression profiles were assessed with RNA sequencing in paws from non-treated CIA mice with different degrees of disease.

Results: Prophylactic administration of anti-IL-20 5B7 starting from either day 0 or day 21 after immunization did not affect the clinical disease activity scores, whereas administration of a TNFα inhibitor decreased disease activity. Histopathological evaluation revealed no effects of anti-IL-20 treatment on i) the degree of synovitis based on scoring of HE stained paw tissues and ii) the number of TRAP+ osteoclasts as an indicator of bone destruction. Analysis of blood samples from CIA mice dosed from day 0 showed that anti-IL-20 treatment did not affect the levels of the pathogenic anti-CII antibodies. The pharmacokinetic profile revealed that the mice have been adequately exposed to anti-IL-20 throughout the experiments and no formation of anti-drug antibodies was detectable. IL-20 mRNA expression data from the paws and lymph nodes of non-treated CIA mouse with varying degrees of arthritis (mild, moderate, severe) showed a very low level of IL-20 mRNA expression in all analysed paws. Importantly, there was no correlation to disease activity in the individual paws. The level of mRNAs for IL-20R1 and IL-20R2 were also low and indicated a negative correlation with paw disease scores.

Conclusion: Very low expression of IL-20 locally in the diseased paws and lack of correlation with disease severity may explain the lack of efficacy of anti-IL-20 treatment in the mouse CIA model. In contrast to previous data showing that anti-IL-20 treatment decrease disease activity in the rat CIA model, our findings indicate that IL-20 does not play a pathogenic role in the mouse CIA arthritis model.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-20-is-not-involved-in-mouse-collagen-induced-arthritis/