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Background: 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. Objectives: To study the association between serum IFNα level, remission and risk of relapse. Methods: 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. Results: 345 samples were obtained from patients in remission. 28.6% of the patients in clinical remission on treatment (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 complete remission on treatment (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 Conclusion: 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. References: [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. Disclosure of Interests: None declared

Background Dysthyroid myopathy (DM) refers to Graves’ ophthalmopathy (GO) in 90% of the cases but can also be observed with hypothyroidism, and is responsible for orbital fat and muscles inflammation. In those patients with euthyroidism and no thyroid receptor antibody, a strong argument for DM can be the aspect of the extra ocular muscles. In myositis of other causes, muscle insertions are increased in size. In DM, the insertions are respected and not increased in volume in magnetic resonance imaging. This was the case of our eight patients. Objectives To describe the efficacy of Tocilizumab (TCZ) in RDM in 8 patients Methods We conducted a monocenter study of 8 patients with RDM refractory to conventional treatment scheme All patients have been treated following the EUGOGO (European Group on Graves’ Orbitopathy) scheme, which consists in weekly infusions of 500 mg prednisolone (4 to 6) followed by weekly infusions of 250 g (4 to 6). One patient had received before oral prednisolone, which is known to be less effective and no other immunosuppressive therapy. The aim was to reduce the clinical activity score (CAS) of the disease to a score of 1 (score composed of 7 items) Results We studied 8 female patients (16 eyes); mean age at diagnosis 64,37±9,37 years. All patients had normal thyroid function at diagnosis.Three patients had a previous history of hashimoto’s thyroiditis and the other 5 had no immunological abnormalities. The duration of orbitopathy between first supposed manifestations and therapy onset was 5,7 months +/- 2,3. TCZ was introduced at the end of the steroid pulses, or before, during steroid therapy, in 2 patients who did not improve at all their ocular status after 3 steroid infusions. TCZ was used intravenously as a monotherapy, at the classical dosage of 8 mg/kg per infusion, with no other immunosuppressives. According to the classification of severity of the EUGOGO group using the CAS 1, before TCZ, 1 had severe (n=2 eyes) or moderate (n= 14 eyes) disease. Moreover, patients presented exophthalmos (n=16 eyes), strabismus (n=16 eyes), muscle inflammation and volume increase at MRI and severe optic neuropathy (n=1). After a mean of 4 pulses (extremes 1 to 7), all patients experienced improvement with TCZ withdrawal in all due to complete remission in 3 and regression in ocular inflammation in 5. Unfortunately, one patient relapsed two months after the 6th TCZ infusion, despite of initial complete remission and was treated with 4 weekly infusions of rituximab at 375 mg/m 2 with a very good response three months later. Only one patient experienced a severe anal abcess after the first TCZ infusion leading to treatment interruption, but with a good improvement of DM. Improvement of ocular parameters with TCZ therapy. Data are expressed as mean±SD or median [IQR]. (VA : visual acuity; IOP : intra ocular pressure; CAS : clinical activity score) Before tocilizumab after tocilizumab VA 0,7 (0,3-1) 0,9 (0,7-1) IOP 26,5 +/-7,7 21,1+/-13 CAS 4,25 +/- 1,28 1 Conclusion TCZ seems to be effective in RDM, as previously reported. In case of ineffectiveness or relapse, rituximab may be effective as well. This questions us about a new treatment scheme, which patients could benefit from biotherapies alone for a better and quicker efficiency? References [1] - Dolman PJ. Grading Severity and Activity in Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg. 2018;34(4S Suppl 1):S34-S40 Disclosure of Interests Philip Bielefeld Consultant for: ABBVIE, Speakers bureau: ABBVIE, Florian Baudin: None declared, Julie Blanc: None declared, Alain Bron: None declared, Suzanne Mouries-Martin: None declared, Romain Bouvet: None declared, Herve Devilliers: None declared

Background To date, anti-dsDNA–Ab titration, better achieved with the Farr test, has been used to monitor global disease activity in systemic lupus erythematosus (SLE). Indeed, anti-DNA–Ab-positivity is associated with overall SLE activity. However, the sensitivity and specificity of that association are relatively low. The close association between Interferon alpha (IFNα) expression and SLE activity suggests that monitoring this cytokine might help physicians better evaluate disease activity. Unfortunately, no reliable simple or standardised assays to quantify IFNα are available in routine clinical practice. The new single-molecule array (Simoa) assay, also called digital ELISA, enables direct IFNα quantification at attomolar (i.e. fg/mL or 10–15 moles/mL) concentrations corresponding to 5,000-fold–increased sensitivity over commercial ELISAs. Objectives We hypothesised that serum-IFNα levels determined with this new standardised assay would be a better biomarker of SLE activity than the Farr test, still considered the “gold standard” for this purpose. The primary objective of this study was to characterise the relationship between digital ELISA-determined serum-IFNα concentrations and clinically assessed SLE activity. We also compared that assay to a functional, sensitive biological assay (bioassay), based on IFNα antiviral properties, used routinely in our institution for 30 years. Methods IFNα concentrations in serum samples from 150 consecutive SLE patients and 68 healthy donnors in a cross-sectional study were determined with the digital ELISA and the bioassay. For SLE patients, clinical characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapeutic regimen, Farr assay, C3 levels and other usual biological parameters were recorded on the day of the blood draw. Results Based on healthy blood donors, the abnormal serum-IFNα level threshold value was 136 fg/mL. Next, using receiver operating characteristics curves for an SLE-patient series, widely heterogeneous for disease activity and organ involvement, the threshold IFNα value associated with active disease was 266 fg/mL. The digital ELISA-assessed serum-IFNα level was a better biomarker of disease activity than the Farr test: its specificity, positive likelihood ratio and positive-predictive value better discerned active SLE and a flare. The digital ELISA was more sensitive than the bioassay to detect low-abnormal serum-IFNα concentrations and patients with low disease activity. In multivariate analyses, abnormal digital ELISA-determined IFNα concentrations were significantly associated with SLE-specific fever, active mucocutaneous lupus, active lupus nephritis and anti-Sm Abs but no other anti-ribonucleoprotein Abs (i.e., anti-Ro/SSA 52, anti-Ro/SSA 60, anti-La/SSB and anti-RNP). Conclusions Direct serum-IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment. Disclosure of Interest None declared