P175 MASTERPLANS: prediction of response to rituximab in SLE using a validated two-score system for interferon

Rituximab is used for resistant SLE, but clinical response varies. We previously validated two interferon-stimulated-gene expression scores (IFN-Score-A and IFN-Score-B) that improved prediction of clinical outcomes in SLE. IFN-Score-A included most reported ISGs and predicted flares and glucocorticoid requirements. IFN-Score-B included ISGs that respond to multiple IFN subtypes and predicted development of SLE in At-Risk individuals. Diagnosis of SLE was associated with both scores, while only IFN-Score-B was elevated in RA. The British Society for Rheumatology Biologics Registry (BILAG-BR) collects samples for RTX-treated patients in the UK. MASTERPLANS ISA consortium to identify predictors of drug response.

Patients were recruited if they were starting a first cycle of RTX for active SLE (BILAG A or 2xBILAG B) despite previous cyclophosphamide or mycophenolate mofetil. Disease activity was measured using BILAG-2004. Clinical response was defined as improvement by > =1 grade in active BILAG-2004 systems with no worsening in other systems. Whole blood was collected into TEMPUS tubes and RNA extracted. IFN-Scores were measured using a custom Taqman array as previously described [El Sherbiny et al., 2018]. Multivariate logistic regression was used to test IFN-Scores and baseline clinical covariates as predictors of BILAG response at 6 months.

Samples were available from 147 patients, of whom 84 had complete baseline and 6-month clinical data available and were included in this analysis. 40/84 (47.6%) patients had BILAG response at 6 months. In univariate and multivariate analysis, high IFN-Score-B expression was significantly associated with clinical response (see Table 1).

This preliminary analysis suggests that assessment of IFN activity has a role in predicting response to RTX. A novel IFN score (Score B) was more predictive than classic ISGs (Score A). These results add to a body of work showing that IFN-Score-B predicts clinically significant outcomes independently of overall IFN activity. Future work will analyse this biomarker in a larger cohort of patients and integrate with other putative clinical and biological predictors of response.

A. Alase None. Z. Wigston None. A. Burska None. M. Md Yusof None. J. Reynolds None. M. Wittmann None. I. Bruce None. E.M. Vital None.