FRI0102 Reduction of antidrug antibody levels after switching to rituximab in patients with rheumatoid arthritis with previous failure to infliximab or adalimumab

Background Rituximab (Rtx), a monoclonal antibody against CD20+, induces transient depletion of B cells and was approved for the treatment of patients with active rheumatoid arthritis (RA). Previous data 1 showed that Rtx is particularly effective on autoimmune diseases in which auto-antibodies (auto-Ab) are produced. Based on this, it is hypothesised that auto-Ab produced by short-lived plasma cells expressing CD20 are targets of Rtx. Given this scenario, the immunogenicity related to the use of Infliximab (Ifx) or Adalimumab (Ada) could be cleared by Rtx. Objectives First, to analyse the persistence of anti-drug antibodies (ADA) after switching to either a 2nd biological therapy (TNFi or Rtx) after 12 months of follow-up. Second, to evaluate whether the reduction of ADA levels are influenced by the mechanism of action of the second biological therapy (BT). Methods Dataset from a prospective cohort including all patients with RA starting BT at the Unit of Complex Therapy in a tertiary hospital was used. For this study, data from 21 patients who had experienced previous failure to Ifx (57%) or Ada (43%) related to ADA detection and then switched to a 2nd TNFi (Ifx, Ada, Etanercept or Certolizumab) or to Rtx was analysed. Additionally, patients should have both determinations of ADA levels: at the end of the first BT and 12 months after switching. ADA were determined by a bridging ELISA. The proportion of patients with ADA positive levels at 12 months was determined. Also, the relative reduction (in median) of ADA levels between patients switching to a 2nd TNFi vs Rtx in both visits was compared. Results Out of 21 ADA positive patients with RA, 15 (71%) switched to a 2nd TNFi and 6 (29%) to Rtx. Demographic characteristics of patients are shown in table 1. ADA remained positive in 80% of patients at 12 months after switching BT. The percentage of patients with undetectable ADA levels at 12 months was higher in the group of patients treated with Rtx compared with patients receiving a 2nd TNFi (33% vs 13%, respectively). The median ADA levels (AU/ml) values at baseline and at 12 months were 536 and 123 for Rtx and 3625 and 1842 for TNFi. The relative reduction of median ADA levels between baseline and 12 months visits was higher in patients with Rtx than in patients treated with TNFi (−78% vs −50%, respectively). Conclusions Despite discontinuing TNFi, ADA titters remain positive in a high proportion of patients with RA after one year. Over time, ADA levels decrease in patients who switch to a second BT, being this effect more pronounced in patients receiving Rtx than a 2nd TNFi. This effect could be explained by the intrinsic action mechanism of Rtx on plasmatic CD20 +cells. Reference [1] Huang H, et al. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. PNAS2010Mar 9;107(10):4658–63. Disclosure of Interest None declared