P163 Association between biomarkers and therapeutic pathway in patients with SLE
Authors: Hassan Sabih Ul , Mahmoud Khaled , Carter Lucy , Dutton Katherine , Li Danyang , Bruce Ian N , McHugh Neil ,   The MASTERPLANS Consortium, Wigston Zoe , Emery Paul , Psarras Anthony , Yusof Yuzaiful , Vital Edward 
Published: April 2021

Background/Aims 

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.

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 (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. 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.

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. P163 Table 1:CharacteristicCYC/RTX=Yes n(%)CYC/RTX =No n(%)Univariable Hazard ratio (95% CI)Univariable p valueMultivariable Hazard Ratio (95% CI)Multivariable p valueAgeQ1: under 2822 (71%)9 (29%)2.25 (0.99,5.12)0.0541.74 (0.95,3.18)0.074Q2: 28-3812 (39%)19 (61%)1.03 (0.41,2.56)0.949Not includedNot includedQ3: 38-5212 (39%)19 (61%)1.52 (0.62,3.72)0.360Not includedNot includedQ4: over 528 (26%)23 (74%)referencereferenceNot includedNot includedEthnicityCaucasian42 (48%)46 (52%)1.17 (0.58,2.35)0.660Not includedNot includedAfroCaribbean, South Asian, East Asian, Other10 (36%)18 (64%)referencereferenceNot includedNot includedIFN Score A, mean (SD)–2.59 (–2.67)–3.84 (–2.71)1.10 (0.98,1.24)0.113Not includedNot includedIFN Score B, mean (SD)–2.61 (–1.16)–3.53 (–1.76)1.31 (1.05,1.64)0.0171.23 (0.98,1.55)0.079Anti-Sm/U1RNP Ab positive17 (61%)11 (39%)1.50 (0.84,2.67)0.171Not includedNot includedAnti-Ro(60) Ab positive14 (45%)17 (55%)0.88 (0.47,1.65)0.686Not includedNot included

Disclosure 

S. Hassan: Grants/research support; S.U.H. is funded as NIHR Leeds Biomedical Research Centre Research Fellow. K. Mahmoud: None. L. Carter: None. K. Dutton: None. D. Li: None. I.N. Bruce: None. N. McHugh: None. T. Consortium: None. Z. Wigston: None. P. Emery: Consultancies; P.E. has received consultant fees from BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB. Grants/research support; P.E. has received research grants paid to his employer from Abbott, BMS, Pfizer, MSD and Roche. A. Psarras: None. M. Md Yusof: Grants/research support; M.Y.M.Y. is funded as a Wellcome fellow. E. Vital: Honoraria; E.M.V. has homoraria from Roche, GSK and AstraZenica. Grants/research support; E.M.V. has research grant support from Roche, GSK and AstraZenica.