FRI0316 The presence of anti-rituximab antibodies predicts infusion-related reactions in patients with systemic lupus erythematous
Authors: C. Wincup, M. Menon, E. Smith, E.C. Jury, D.A. Isenberg, C. Mauri
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody commonly used in the treatment of a variety of autoimmune rheumatic conditions. Although generally well tolerated, serious infusion related reactions can occur and are difficult to predict. It has previously been suggested that patients with systemic lupus erythematosus (SLE) who are treated with Rituximab demonstrate a higher incidence of infusion reactions and a less predictable response to the therapy when compared with other diseases. A major limitation of biologic therapies is the development of anti-drug antibodies (ADA). To date the presence of ADAs to Rituximab have not previously been explored in detail. <h3>Objectives</h3> To assess the prevalence of ADAs to Rituximab in patients receiving treatment for SLE and how the presence of these antibodies relates to: 1. the incidence of infusion-related reactions 2. the therapeutic efficacy of the drug <h3>Methods</h3> We assessed the presence of Rituximab ADAs using a Meso Scale Discovery platform in 58 SLE patients treated with Rituximab at University College London Hospital, UK. A subgroup of 42 patients were followed up longitudinally for up to 8 years after their first dose of Rituximab. Clinical parameters including BILAG, complement C3 levels, anti-double-stranded DNA (dsDNA) antibody titres, lymphocyte count and frequency of CD19<sup>+</sup> B cells were recorded. A retrospective review of patient notes was undertaken to assess for a history of infusion related reactions. Mann-Witney U test was used to compare variables between the ADA positive group and ADA negative group. <h3>Results</h3> A total of 58 patients were recruited of which 88% were female (51/58). Median age was 38.9 years old with a median disease duration of 84 months. ADAs to Rituximab were detected in 60% (35/58) of patients. In those with a positive ADA (n=35), 22 were later retreated with Rituximab. Infusion reactions were noted in 68% (15/22) of those undergoing retreatment in the context of a previously positive ADA. In the remaining patients who were retreated but in which no infusion reaction was seen (7/22), the average level of ADA was significantly lower than in those who did have a reaction (median in those who suffered a reaction=200 unit; median in those who were ADA positive but did not develop a reaction on retreatment=10 units; p=0.008). There were no reactions observed in patients that did not display ADAs who were subsequently retreated. In the first six months post-Rituximab there was no statistically significant difference in BILAG, C3 levels, dsDNA titres, lymphocyte count or CD19 between the groups in which ADAs were present when compared with those in which ADAs were absent. <h3>Conclusions</h3> For the first time, ADAs to Rituximab have been described in a cohort of SLE patients who have undergone B-cell depletion therapy. High levels of circulating ADAs to Rituximab were found in patients who later developed infusion reactions on retreatment. However, there was no obvious difference in clinical outcomes between those who were ADA positive compared with those in which it was negative. Together, this suggests the presence of ADAs can predict future infusion reactions but do not adversely impact upon the efficacy of treatment. In future, the routine screening of ADAs to Rituximab will help to reduce the risk of serious infusion reactions in patients being treated. <h3>Disclosure of Interest</h3> None declared