THU0227 BIOLOGICAL MONITORING OF REMISSION IN SYSTEMIC LUPUS ERYTHEMATOSUS: ABNORMAL SERUM INTERFERON-ALPHA LEVELS PREDICT RELAPSE
Authors: Suzanne Mouries-Martin, Alexis Mathian, Hervé Devilliers, Karim Dorgham, Delphine Sterlin, Fleur Cohen, Julien Haroche, Miguel Hié, Marc Pineton de Chambrun, Makoto Miyara, Micheline Pha, Du Boutin-Le Thi Huong, Flore Rozenberg, Guy Gorochov, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Remission and relapses prevention are the main objectives of the treatment of Systemic Lupus Erythematosus (SLE). Interferon alpha (IFNα) is a key cytokine in SLE, but its usefulness for the definition of remission and for the prediction of flare has not been validated in clinical practice. <h3>Objectives:</h3> To study the association between serum IFNα level, remission and risk of relapse. <h3>Methods:</h3> 502 SLE patients were assessed for serum IFNα level using a biological functional assay(1). Remission was defined by the absence of clinical manifestation of lupus activity (clinical SELENA-SLEDAI = 0) and a prednisone intake ≤ 5 mg/day(2). Patients in remission were subsequently followed for one year. The SELENA-SLEDAI Flare Index was used to identify SLE flare. Uni- and multivariable analyses were performed to define disease parameters associated with serum IFNα positivity in patients in remission at baseline. Survival curve analysis, log-rank tests and Hazard Ratios (HR) were calculated to evaluate the risk of flare depending on IFNα, dsDNA Abs and C3 levels at baseline. <h3>Results:</h3> 345 samples were obtained from patients in remission. 28.6% of the patients in <i>clinical remission on treatment</i> (requiring clinical SELENA-SLEDAI = 0, positive anti-dsDNA antibodies and/or C3 decrease and prednisone intake 1 – 5 mg/day) had an abnormal serum IFNα level, compared to 6.5% of the patients in <i>complete remission on treatment</i> (requiring clinical SELENA-SLEDAI = 0, no anti-dsDNA antibodies nor C3 decrease and prednisone intake 1 – 5 mg/day). In patients in remission, high serum IFNα levels at baseline were associated in multivariable analysis with the positivity of anti-dsDNA Abs (HR 3.4 [95%CI 1.6-7.2], p=0.0001) and anti-RNP Abs (HR 3.2 [95%CI 1.5-6.8], p=0.0002). In patients in remission, high serum IFNα level at baseline was a significant and independent risk factor of lupus flare (HR=4.8 [95%CI 2.3-9.7], p&lt;0.0001). Low C3 was also associated with the risk of relapse with a HR=3.2 [95%CI 1.4-7.0], p=0.005, but positive anti-dsDNA Abs was not (HR=1.8 [95%CI 0.9-3.6], p=0.1). <h3>Conclusion:</h3> A large number of SLE patients in remission display abnormal levels of serum IFNα. Abnormal levels of serum IFNα in patients in remission were significantly associated with positive anti-dsDNA and anti-RNP Abs and were an independent predictive biomarker of lupus flare in the following year. Adding serum IFNα to the routine laboratory assessments perform in patient in remission could help clinicians to identify a subgroup of SLE patient clinically in remission but serologically active and at higher risk of relapse. <h3>References:</h3> [1] Mathian A, et al. Monitoring disease activity in systemic lupus erythematosus with single-molecule array digital ELISA quantification of serum interferon-α. Arthritis Rheumatol Hoboken NJ.2018Dec3; [2] Vollenhoven R, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017Mar1;76(3):554–61. <h3>Disclosure of Interests:</h3> None declared