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Background:Graves’ Orbitopathy (OG) is the main extrathyroid manifestation of Graves’ disease (GD). Up to 25% of patients have moderate-severe inflammatory activity with a risk of major sequelae. Intravenous (i.v.) glucocorticoids (GC) pulses are the standard therapy. In refractory cases, several classic and some biological immunosuppressantsare used, obtaining variable responses. Interleukin 6 (IL6) is involved in the pathogenesis of OG, which has justified the off-label treatment with Tocilizumab (TCZ)1, whose use by route i.v. has shown favorable results in published small case series and a single multicenter trial2.Objectives:To analyse the ocular effectiveness of anti-IL6 therapy used subcutaneously (s.c.) in patients with moderate-severe active refractory OG in usual clinical practice.Methods:Retrospective descriptive observational study of a series of cases of moderate-severe OG patients treated with anti-IL6 s.c. The patient medical records of those who had received at least 1 cycle of anti-IL6 treatment were reviewed (December 2013-December 2019). The primary effectiveness outcome was the change of the Clinical Activity Score (CAS). Favorable response was considered: reduction of CAS≥2 points together with obtaining inactivity (CAS <3). Demographic data, personal medical history, clinical aspects of GD, previous therapies and data on the use and safety of anti-IL6 were collected. The SPSS11 package was used for statistical analysis, using non-parametric tests for quantitative variables. The study was approved by the local Ethical Committee.Results:12 of the 15 patients (80%) were women with a mean of 50.27 years (21-72). 60% (n=9) had smoking history, 40% (n=6) active. 26.7% (n=4) were diabetic, all without retinopathy. 100% of patients received imidazole antithyroid treatment. 46.7% (n=7) required β-blockers and 20% (n=3) diuretics. 66.7% thyroidectomy (n=10) and 20% (n=3) decompressive eye surgery and/or blepharoplasty were performed. Thyroid and ocular radiotherapy were used in 2 patients. 3 patients received botox. 80% (n=12) of them had previously received GC. 93.3% (n=14) were naïve to biological therapy, only 1 patient previously used Rituximab. All except one patient who was treated with SRL received TCZ as IL6 therapy. A significant favorable response was obtained in 100% of the patients (p=0.008), decreasing CAS average from 4.9 (2-7) to 1.7 (0-2) at the end of the therapy [Figure 1]. The severity of the OG changed from being moderate in 72.7% of the patients to mild in 66.7% of the total. The median time to inactivity was 8 months (2-15). 73.3% (n=11) of the patients finished the treatment reaching inactive OG, the rest (although inactive) maintained therapy. After 6 months, 100% of those who completed the treatment remained inactive with average CAS of 1.3 (0-2). Smoking did not influence the response, nor any other variable collected. Adverse events appeared in 26.7% (n=4) of the cases, all of them mild and without widrawal.Conclusion:Treatment with anti-IL6 s.c. steadily decreases the clinical activity measured by CAS in patients with moderate-severe refractory OG, despite poor prognosis factors (such as smoking), with a good safety profile.References:[1]Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves’ orbitopathy. Nat Rev Endocrinol. 2020 Feb;16(2):104-116.[2]Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, Perez-Pampin E, Romo Lopez A, Rodríguez Álvarez FM, et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Gravesˊ Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol. 2018;195:181–90.Disclosure of Interests:None declared

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Background:Tocilizumab (TCZ) is the only biological agent approved in Giant Cell Arteritis (GCA). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is scarce.Objectives:Our aim was to assess efficacy and safety of TCZ therapy optimization in an unselected wide series of GCA in clinical practice.Methods:Multicenter study, 134 patients with GCA who received TCZ due to inefficacy/adverse events of previous therapy. Once complete remission was reached and based on a shared decision between patient and physician TCZ was optimized in some cases. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively.Results:134 GCA patients treated with TCZ (101w/33m); mean age 73.0±8.8 years. TCZ was administered IV to 106 (79.1%) patients and SC to 28 (20.9%). TCZ was optimized in 43 (32.1%) patients. No demographic, clinical manifestations or laboratory data differences had been found at TCZ onset (TABLE). After a follow up of 12 [6-15.5] months, and a complete remission for 6 [3-12] months; the first TCZ optimization was performed. Median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. TCZ IV was optimized from 8 to 4 mg/kg/4weeks in 12 of 106 (11.3%) and from 162 mg/SC/week to 162 mg/SC/2weeks in 9 of 28 (32.1%) cases. Five (11.6%) of the 43 optimized cases relapsed. In 4 cases, the relapses were treated increasing TCZ up to the pre-optimization dose, in 1 case the route of administration was change (4 mg/kg/4week to 162 mg/SC/week). In 8 of 43 optimized patients (18.6%), it was possible to withdraw TCZ after complete remission for 30 [16.25-45.75] months. Regarding adverse events and severe infections were similar in both groups. The mean TCZ treatment costs were lower in the optimized group.Conclusion:Once remission is reached in GCA patients under TCZ treatment, optimization of TCZ may be performed. Based on our experience it could be performed by reducing the dose with IV TCZ or by prolonging dosing interval with SC TCZ.References:[1]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLE.OPTIMIZED-TCZ GROUP (n=43)NON-OPTIMIZED TCZ GROUP (n=91)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURESAge, years, mean± SD68.9±8.771.4±8.50.125Sex, female/male n(%)32/1068/240.779Time from GCA diagnosis to TCZ onset (months), median [IQR]19.5[7.75-45]10.5[4 – 25]0.047SYSTEMIC MANIFESTATIONSFever, n(%)1(2.4)8(8.7)0.176Constitutional syndrome, n(%)11(26.2)19(20.7)0.476PMR, n(%)18(42.9)56(60.9)0.052ISCHEMIC MANIFESTATIONSVisual involvement, n(%)5(11.9)23(25)0.084Headache, n(%)26(61.9)42(45.7)0.081Jaw claudication, n(%)1(2.4)11(12)0.072CORTICOSTEROIDS AT TCZ ONSETPrednisone dose, mg/d mean (SD)15.1±11.125±17.40.001FOLLOW-UP ON TCZ THERAPY (MONTHS), MEDIAN [IQR]24[18-27]6 [3-18]0.000Relapses, n(%)5(11.6)5(5.5)0.207End follow-up remission, n(%)40(93)84(92)0.99Severe side efects, n(%)14(32.6)22(24.2)0.307Seriuos infections, n(%)6(14)10(11)0.878Cost, (mean) euros per yearIVSC7 538.47 329.011 726.411 726.4--Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Factors associated with the development of chronic heart failure (CHF) in systemic lupus erythematosus (SLE) have received little attention. On the other hand, recent data from the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection during the COVID19 pandemic have cast some doubts on its cardiological safety.Objectives:To identify factors associated to CHF in SLE.Methods:Retrospective cross-sectional study, including all patients with SLE (≥4 ACR-1997 criteria) recruited in RELESSER registry. The objectives and methodology of the registry have been described previously (1). CHF was defined according to the Charlson index item. Patients with CHF before diagnosis of SLE were excluded. Cumulative damage was measured with the SLICC/ACR index, excluding cardiovascular (CV) items (mSDI). Multivariate analysis exploring factors associated with CHF was carried out.Results:117 patients (3% of the entire cohort) with SLE and CHF and 3,506 controls with SLE without CHF were included. 90% were women. Disease duration: mean (SD), 120.2 (87.7) months. CHF appeared after a median (P25-P75) of 9.40 (4.2-18.3) years from SLE diagnosis. Patients with CHF were older (59.8 ± 18.2 vs. 46.2 ± 4.3). In the bivariate analysis, the association of CHF with greater severity [Katz severity index: median (IQR): 4 (3-5) vs. 2 (1-3)], damage [mSDI: 3 (2-4) vs 0 (0-1)], comorbidity [modified Charlson- excluding CV items: 4 (3-6) vs 1(1-3)] and both CV (37.5% vs 6.7%) and overall mortality (43.2% vs 4.7%) (p<0.0001 for all comparisons). Also, CHF patients were more refractory to SLE treatments (33.3% vs 24%, p=0.0377) and were more frequently hospitalised due SLE [median 3 (1-5) vs 1(0-2), p<0.0001]. The results of the multivariable model are depicted in table 1.Table 1.Congestive heart failure associated factors (multivariable analysis)Odds Ratio95% CIP-valueSex (female)0.460.25 - 0.880.0147Ischaemic cardiopathy7.964.01 - 15.48<0.0001Cardiac arrhythmia7.384.00 - 13.42<0.0001Pulmonary hypertension3.711.84 - 7.250.0002Cardiac valvulopathy6.333.41 - 11.62<0.0001Hospitalization (due to SLE)3.741.81 - 8.650.0008Calcium or vitamin D5.292.07 - 16.860.0015Antimalarials0.280.17 - 0.45<0.0001mSDI *1.291.16 - 1.44<0.0001*mSDI = modified SLICC/ACR damage index (without cardiovascular items)Conclusion:- CHF is a rather late complication of SLE.- Patients with SLE and CHF have more severe SLE, with greater refractoriness to SLE treatments and higher overall mortality.- Treatment with antimalarials, as routinely used in SLE patients, is not only safe to heart, but even appears to have a cardioprotective effect.References:[1]Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, et al. National registry of patients with systemic lupus erythematosus of the Spanish Society of Rheumatology: objectives and methodology. Reumatol Clin. 2014;10(1):17-24.Acknowledgements:Research Unit of Spanish Society of RheumatologyDisclosure of Interests:None declared