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[Abstract] Introduction: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. Ethics and dissemination: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. Trial registration number: 2020-000130-18; NCT04798755. This work was supported by the Instituto de Salud Carlos III, grant number [ICI19/00020]. Sponsor: Fundación para la Investigacion Biomédica del Hospital Clínico San Carlos. Executive Committee: Administrative and executive arm of the clinical trial, providing overall oversight for the study and making decisions on day-to-day operational issues (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado), and 5 Site Directors (these seats will be rotatory, with changes every 6 months months)); Data Coordinating and Analysis Committee: Supervising data collection,management and quality control, designing the statistical analysis plan, performing unmasked data analysis and preparing interim and final reports for the Data Security Monitoring Board and the Executy Committee (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado) and Ester Carreño); Biobank and Biomarker Identification Committee (Maintaining an up-to-date manual of operations for blood extraction, processing and storage, and monitoring procedures adherence, supervising biological sample collection, sample shipment coordination, coordinating the phamacogenetic and proteomic analysis (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Instituto de Salud Carlos III Biobank Platform (Elena Molino), a representative the Instituto de Investigación Biomédica de A Coruña, a representative from, the Data Coordinating and Analysis Committee); Data Security Monitoring Committee (PierGiogio Neri, Andrew Dick, Loreto Carmona)

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age 64 years group, OR was 20.610 (4.679-90.774, p 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age 64 years, OR was 7.674 (1.675-35,151, p 0.009); disease duration, OR 1.049 (CI 1.003-1097, p 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.

Background Uveitis is one of the major causes of disability of Behcet’s disease (BD). According to the “Expert panel recommendations”, anti-TNF therapy with infliximab (IFX) or adalimumab (ADA) may be considered as first- or second-line therapy for patients with BD-ophthalmic manifestations. Objectives To compare IFX versus ADA as first biologic drug in refractory uveitis due to BD for 1-year period. Methods Multicenter study of BD-associated uveitis refractory to conventional non-biologic treatment. Dosing schedule: IFX 3-5 mg/kg iv at 0, 2 and 6 weeks and then every 4-8 week, and ADA 40 mg/sc/every other week without loading dose. Main comparative outcome measures: safety and efficacy, assessing the intraocular inflammation, macular thickness, visual acuity, degree of immunosuppression load, drug retention, and glucocorticoid-sparing effect. Results 177 patients (316 affected eyes) were included. IFX was used in 103 and ADA in 74. No significant differences at baseline were observed regarding main demographic features, previous therapy and ocular severity. After 1 year of therapy, we observed an improvement in all ocular parameters in IFX vs ADA groups: AC inflammation (78.18% vs 92.31%), vitritis (78.95% vs 93.33%), retinal vasculitis (97% vs 95%), macular thickness (264.89±59.74 vs 250.62±36.85), and BCVA (0.67±0.34 vs 0.81±0.26). Drug withdrawal was observed in 57 (55.33%) of IFX group and in 21 (28.37%) of ADA group. Conclusion After 1 year of therapy in refractory BD-associated uveitis, ADA showed a statistically better outcome than IFX in improvement of BCVA, vitritis and drug retention. References [1] Levy-Clarke G, et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014; 121:785-96. [2] Santos-Gomez M, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol 2016; 34 (6 Suppl 102): S34-40 [3] Atienza-Mateo B, et al. Anti-IL6-Receptor Tocilizumab in Refractory Uveitis Associated With Behcet’s Disease. Multicenter Retrospective Study. Rheumatology (Oxford). 2018 May 1;57(5): 856-864. [4] Martin-Varillas JL, et al. Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behcet’s Disease. Ophthalmology. 2018 Mar 27. Disclosure of Interests Belen Atienza-Mateo: None declared, Jose Luis Martin-Varillas: None declared, Vanesa Calvo-Rio: None declared, Rosalia Demetrio-Pablo: None declared, Emma Beltran: None declared, Juan Sanchez-Burson: None declared, Marina Mesquida: None declared, Alfredo Adan : None declared, Victoria Hernandez: None declared, Marisa Hernandez-Garfella: None declared, Elia Valls-Pascual: None declared, Lucia Martinez-Costa: None declared, Agusti Sellas-Fernandez: None declared, Miguel Cordero-Coma: None declared, Manuel Diaz-Llopis: None declared, Roberto Gallego: None declared, Jose L. Garcia-Serrano: None declared, Norberto Ortego: None declared, Jose M. Herreras: None declared, Alejandro Fonollosa: None declared, Angel Garcia-Aparicio: None declared, Olga Maiz-Alonso Speakers bureau: Pfizer, Ana Blanco: None declared, Ignacio Torre-Salaberri: None declared, Cruz Fernandez-Espartero: None declared, Vega Jovani: None declared, Diana Peiteado: None declared, Esperanza Pato: None declared, Juan Cruz: None declared, Carlos Fernandez-Cid: None declared, Elena Aurrecoechea: None declared, Miriam Garcia-Arias: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Miguel A. Caracuel-Ruiz: None declared, Carlos A. Montilla-Morales: None declared, Antonio Atanes-Sandoval: None declared, Felix Francisco: None declared, Santos Insua: None declared, Senen Gonzalez-Suarez: None declared, Amalia Sanchez-Andrade: None declared, Fernando Gamero: None declared, Luis F. Linares Ferrando: None declared, Fredeswinda Romero: None declared, A. Javier Garcia-Gonzalez: None declared, RAQUEL ALMODOVAR: None declared, Enrique Minguez: None declared, Carmen Carrasco-Cubero: None declared, Alejandro Olive: None declared, Julio Vazquez: None declared, Oscar Ruiz-Moreno: None declared, Fernando Jimenez-Zorzo: None declared, Javier Manero: None declared, Santiago Munoz Fernandez: None declared, Cristina Fernandez-Carballido: None declared, Esteban Rubio-Romero: None declared, Fred Anton Pages: None declared, Francisco J. Toyos Saenz de Miera: None declared, Myriam Gandia Martinez: None declared, David Diaz Valle: None declared, Francisco J Lopez-Longo: None declared, Joan Miquel Nolla: None declared, Enrique Raya: None declared, Marcelino Revenga: None declared, J. Luis Hernandez: None declared, Monica Calderon-Goercke: None declared, D. Prieto-Pena: None declared, Inigo Gonzalez-Mazon: None declared, Lara Sanchez Bilbao: None declared, Miguel A. Gonzalez-Gay: None declared, Ricardo Blanco: None declared

Objectives To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. Methods Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. Results A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13−76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4−8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range—IQR) 0.5 (0−2) versus 0 (0−0) ( p = 0.003), vitritis 0 (0−1.25) versus 0 (0−0) ( p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) ( p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0−30)mg at the onset of the anti-TNF-α therapy to 0 (0−0)mg at 2 years ( p = 0.02). Significant reduction was also achieved in the immunosuppressive load. Conclusion Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.