POS0175 ASSOCIATION BETWEEN BIOMARKERS AND THERAPEUTIC PATHWAY IN PATIENTS WITH SLE
Authors: S. U. Hassan, K. Mahmoud, Z. Wigston, A. Burska, M. Y. MD Yusof, E. Vital
Journal: Annals of the Rheumatic Diseases (2021)

Background: SLE is heterogeneous in clinical presentation, underlying immunology, and response to therapy. Patients with severe or resistant disease receive cyclophosphamide or rituximab. Although effective, late use of these therapies entails cumulative damage. Emerging predictors of response to rituximab include demographics, IFN-Scores and autoantibodies. For such predictors to change treatment strategy we need to understand their association with the effectiveness of other therapeutic options at earlier decision points. Prospective studies of treatment pathways are difficult to perform, requiring large populations followed for many years. We therefore investigated this question by analysing retrospective treatment pathways since diagnosis in patients whose biomarker status is subsequently known. Objectives: To use interferon scores and other markers to; [1]identify SLE patients more likely to need escalation of therapy to either rituximab or cyclophosphamide, and [2]determine if this occurred sooner than in others. Methods: In patients with established SLE, attending Leeds SLE clinic, we collected demographics, clinical characteristics and blood at a single timepoint. Two previously validated IFN-Scores[1,2] (IFN-Score A and IFN-Score B) were measured using Taqman. Autoantibodies were measured using immunoprecipitation. Treatment history covering all antimalarials, oral and intravenous immunosuppressants (agent, start and stop dates and reasons) since diagnosis was collected. Univariable and multivariable Cox proportional hazards models were used to test variables as predictors of the primary endpoint: time to cyclophosphamide/rituximab. Results: 124 patients were included. Follow up since diagnosis was Median (IQR) 37.5 (27.4-52.3) years, total therapies per patient was 3 (1-4), therapies per year was 0.2 (0.1-0.3). 54/124 (44%) patients required cyclophosphamide/rituximab. Results of Cox regression are shown in the table 1. There was a significant association between high expression of IFN-Score B and requirement for cyclophosphamide/rituximab as well as trends for age in the first quartile (&lt;28 years), IFN-Score A and anti-Sm/U1RNP antibodies. Both age &lt;28 and IFN-Score B retained trends as independent predictors in a multivariable model. Table 1. Characteristic CYC/RTX=Yes n(%) CYC/RTX =No n(%) Univariable Hazard ratio (95% CI) Univariable p value Multivariable Hazard Ratio (95% CI) Multivariable p value Age -Q1: under 28 22 (71%) 9 (29%) 2.25 (0.99,5.12) 0.054 1.74 (0.95,3.18) 0.074 -Q2: 28 – 38 12 (39%) 19 (61%) 1.03 (0.41,2.56) 0.949 Not included Not included -Q3: 38 – 52 12 (39%) 19 (61%) 1.52 (0.62,3.72) 0.360 Not included Not included -Q4: over 52 8 (26%) 23 (74%) reference reference Not included Not included Ethnicity -Caucasian 42 (48%) 46 (52%) 1.17 (0.58,2.35) 0.660 Not included Not included -AfroCaribbean, South Asian, East Asian, Other 10 (36%) 18 (64%) reference reference IFN Score A, mean (SD) −2.59 (−2.67) −3.84 (−2.71) 1.10 (0.98,1.24) 0.113 Not included Not included IFN Score B, mean (SD) −2.61 (−1.16) −3.53 (−1.76) 1.31 (1.05,1.64) 0.017 1.23 (0.98,1.55) 0.079 Anti-Sm/U1RNP Ab positive 17 (61%) 11 (39%) 1.50 (0.84,2.67) 0.171 Not included Not included Anti-Ro(60) Ab positive 14 (45%) 17 (55%) 0.88 (0.47,1.65) 0.686 Not included Not included Conclusion: Patients developing SLE before age 28 with raised interferon scores may be forecast to develop severe disease, fail oral therapies, and require rituximab. While this retrospective analysis may be confounded by a survivorship bias, our findings are consistent with other literature on these variables as predictors of severe disease. Future work will analyse more biomarkers in a larger and more varied patient population. References: [1]Md Yusof et al. Ann Rheum Dis 2018 [2]El-Sherbiny et al. Sci Rep 2018 Disclosure of Interests: Sabih-Ul Hassan: None declared, Khaled Mahmoud: None declared, Zoe Wigston: None declared, Agata Burska: None declared, Md Yuzaiful Md Yusof: None declared, Edward Vital Grant/research support from: Honoraria and research grant support from Roche, GSK and AstraZeneca.