OP0134 NOVEL INTERFERON GENE EXPRESSION SCORES PREDICT REFRACTORY SEVERE CUTANEOUS DISEASE FOLLOWING RITUXIMAB THERAPY IN SLE

Background: We developed and validated two continuous interferon-stimulated gene (ISG) expression scores (IFN-Score-A IFN-Score-B) that predict clinical outcomes in SLE. IFN-Score-A includes ISGs typically present a global interferon signature while IFN-Score-B additional potentially responsive to multiple IFN subtypes [1]. have previously shown these associate with treatment response following rituximab (RTX) therapy within the British Isles Lupus Assessment Group (BILAG) Biologics Register (BILAG-BR), UK wide study of patients treated RTX for active SLE cyclophosphamide and/ or mycophenolate mofetil failure. Specifically, multivariable analysis showed higher baseline independently predicted BILAG at 6 months post [2]. also cutaneous lupus can be poor even when other organs respond well, interferons are enriched skin where dysregulated keratinocytes source IFNк [3]. MASTERPLANS is consortium aimed identifying therapeutic biomarkers Objectives: To investigate how -B associated disease RTX. Methods: Pre-treatment whole blood samples were collected TEMPUS tubes from subjects undergoing first BILAG-BR. IFN-Scores derived using custom Taqman array as described Clinical was defined improvement BILAG-2004 activity, maximum one domain showing persistent grade B disease, no new A flares months. The mucocutaneous then analysed separately. Results: 147 studied, whom 90 had follow up data available. Baseline A/B activity predominantly affected 74/147 (50.3%), musculoskeletal 61 /147 (41.5%) renal 66/147 (37.4%). At 59/90 (65.6%) achieved an overall response. Responders significantly mean compared non-responders (-1.8 vs -2.4, p = 0.04). Among those baseline, 38/50 (76%) this However, among non-responders, 7/31 (22.6%) residual BILAG-A RTX, indicating it substantial component In contrast, seen 9.7% non-responders. characterised by severe manifestations including extensive rashes covering > 18% body surface area, bullous panniculitis disabling deep mucosal ulceration. Neither nor severity baseline. individuals six displayed lower than improving less (-3.0 -2.1, 0.04) after Conclusion: Low score-B status identified endotype which resistant BILAG-BR cohort. high IFN-score-B predicts rituximab. Further work will aim refine organ specific References: [1] El-Sherbiny et al., Sci. Rep. 2018; 8: 5793. [2] Alase ARD 2019;78:763-764 [3] Psarras Nat Commun. 2020; 11: 6149 Acknowledgements: would like thank Medical Research Council, National Institute Health Research, funding project Disclosure Interests: Lucy Marie Carter: None declared, Adewonuola Alase: Zoe Wigston: Antonios Psarras: Agata Burska: Md Yuzaiful Yusof: Elizabeth Hensor: John Reynolds: Miriam Wittmann Consultant of: Abbvie, Celgene, Janssen, L’Oreal, Novartis Pfizer, Ian N. Bruce Speakers bureau: GlaxoSmithKline, UCB Pharma, AstraZeneca, Eli Lilly, ILTOO MedImmune, Merck Serono, Grant/research support from: Genzyme Sanofi, Edward Vital Roche, GSK AstraZeneca