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Background The incidence of sarcoidosis varies widely worldwide. The aim of this study was to estimate the incidence of sarcoidosis in a population-based cohort from northern Spain. Methods Patients diagnosed with sarcoidosis at Marques de Valdecilla University Hospital, corresponding to the central Cantabria that encompasses Santander city and the surroundings, between January 1999 and December 2019were assessed. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. Demographic and clinical data were collected. The incidence of sarcoidosis between 1999-2019 was estimated by sex, age, and year of diagnosis. Results A total of 234 patients were included, with a male/female ratio of 0.81. The mean age of the cohort at diagnosis was 48.43 ± 14.83 years and 129 (55.1%) were women. Incidence during the period of study was 3.58 per 100,000 populations (95% confidence interval: 3.13 – 4.07). No gender predominance was observed. An increase in age at diagnosis over time was found in the linear regression analysis. Thoracic affection was found in 180 patients (76.9%). Most common extra-thoracic areas affected were skin (34.2%), joints (30.8%) and eyes (15.4%). Conclusions The incidence of sarcoidosis estimated in this study was similar to that of other Mediterranean countries. No gender predominance was observed. Consistent with previous studies, male presented an incidence peak 10 years earlier than female. A second peak between ages 60-69 years was identified in both sexes.

Purpose: To describe the clinical and epidemiological characteristics of patients with Vogt-Koyanagi-Harada (VKH) disease in Spain. Methods: This was a retrospective multicenter analysis of data from VKH patients followed for at least 6 months. The data collected were related to demographics, clinical manifestations, treatments, and complications. Results: Participants were 112 patients (224 eyes), from 13 tertiary referral centers, of mean age 37.5 ± 14.7 years; 83.9% were women. Ethnicities were 61.6% Caucasian and 30.4% Hispanic. The disease was classified as complete in 16.1%, incomplete in 55.4%, and probable in 28.6%. When seen for the first time, the clinical course was acute in 69.6%, recurrent chronic in 15.2%, and chronic in 14.3%. The most frequent treatment was corticosteroids (acute stage 42.2%, maintenance stage 55.6%). The most common complications were cataract (41.1%) and ocular hypertension (16.1%). In most eyes, visual acuity was improved (96.7%) or remained stable at the end of follow up. Conclusion: VKH in Spain mostly affects women and presents as incomplete acute stage disease. Visual prognosis is good. Cataract and glaucoma are the two most frequent complications.

Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behcet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

Graves&rsquo, orbitopathy (GO) is the most common extrathyroidal manifestation of Graves&rsquo, disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves&rsquo, Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes), mean age &plusmn, standard deviation 51 &plusmn, 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved, BCVA (0.78 &plusmn, 0.25 vs. 0.9 &plusmn, 0.16, p = 0.0001), CAS (4.64 &plusmn, 1.5 vs. 1.05 &plusmn, 1.27, p = 0.0001) and intraocular pressure (IOP) (19.05 &plusmn, 4.1 vs. 16.73 &plusmn, 3.4 mmHg, p = 0.007). After a mean follow-up of 16.1 &plusmn, 2.1 months, low disease activity (CAS &le, 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

BackgroundInflammatory ocular pathology (IOP) includes internal and external involvement. IOP may be severe ocular conditions refractory to conventional immunosuppressants and even biological therapy. Janus Kinase inhibitors (JAKINIB) had shown efficacy in refractory cases of different immune-mediated inflammatory diseases (IMID).ObjectivesIn patients with refractory IOP treated with JAKINIB our aims were a) to assess the patients of Spanish referral centers, b) Literature review.MethodsMulticenter study of 6 patients with refractory IOP treated with JAKINIB. For Literature review a search was conducted in PubMed, Embase and the Cochrane library from their inception to 1st January 2022, and conference proceedings from four major rheumatology conferences. In addition, a therapeutical approach of refractory IOP is proposed.ResultsWe have identified 6 cases in five University Hospitals and 11 cases in the literature review. These 17 patients (14 women/ 3 men) (24 affected eyes), mean age 35.5±23.4 years had different refractory IOP (uveitis=11; scleritis= 3, PUK= 3).Most of IOP were associated with IMID (n=13, 76.5%). The main underlying IMID were juvenile idiopathic arthritis (n=5, 29.4%), rheumatoid arthritis (n=2, 11.8%) and spondyloarthritis (n=2; 11.8%) (Table 1).Table 1.Cases reports and Literature reviewStudy, yearCasesAge/ SexUnderlying IMIDJAKINIBOcular involvementPrevious immunosuppressive treatmentOcular Improvement(Ref)Meadow et al. 2014159, FRATOFAPUKMTX, ABA, ivMPPartial (PI)(1)Bauermann et al. 2018122, FJIATOFAA. uveitis, CMEMTX, ADA, RTX, GOLI, IFX, CsA, TCZ, MMFComplete (CI)(2)Paley et al. 201921.40, F1.Idiopathic1.TOFA1.Scleritis1.MTX, MMF, AZA, CYP1.CI(3)2.45, F2.Idiopathic2.TOFA2.A. uveitis, CME2.MTX, LFN, AZA, MMF, ADA, IFX, CZP, intravitreal fluocinolone ac.2.CILiu J et al. 2020130, MBehçet disTOFAScleritisSSZ, MTX, AZA, LFN, THD, COL, GLMPI(4)Majumder et al. 2020126, FVogt-Koyanagi- Harada disTOFAP. uveitisivMPCI(5)Miserocchi et al. 202041. 9, FJIA1. TOFA1. Panuv1. IFX, ADA, LFN, ABA, RTX, TCZ.1. CI2. 1, F2. BARI2. Panuv2. MTX, ADA, IFX, RTX, ABA.2. CI(6)3. 2, F3. BARI3. Panuv3. MTX, AZA, IFX, ADA, TCZ.3. CI4. 10, M4. BARI4. Panuv4. ETN, MTX, CsA, IFX, ADA, ABA, TCZ, RTX.4. CIPyare et al. 2020145, FIdiopathicTOFANecrotizing scleritisMMFCI(7)Present study, 202261. 25, F1. Blau Syndrome1. TOFA/BARI1. Panuv1.MTX, ETN, ANA, ABA1. CI2. 85, F2. RA2. BARI2. PUK2.MTX, LFN, CZP, ADA, iv MP.2. CI3. 41, F3. Relapsing polychondritis3. BARI3. PUK3. MTX, CsA, SSZ, MMF, AZA, IFX, TCZ, CZP, ABA, ADA.3. CI4. 65, F4. Idiopathic4. BARI4. Panuv4. MTX, AZA4. CI5. 59, M5. AS5. UPA5. A. uveitis5. MTX, ADA5. CI6. 40, F6. SpA and ulcerative colitis6. TOFA6. A. uveitis6. MTX, AZA, ADA6. CIUveitis (n=11) followed by ocular surface pathology (n=6) were the most frequent subtypes of IOP. Patterns of uveitis were panuveitis (n=6), anterior uveitis (n=4; 2 of them with Cystoid macular edema) and posterior (n=1). Ocular surface pathology was due to scleritis (n=3) and PUK (n=3).Besides systemic corticosteroids, before JAKINIB, conventional (n= 16; 94.1%) and biological immunosuppressive drugs (n=13; 76.5%) were required. The JAKINIB most widely used was tofacitinib (n= 10; 58.8%) followed by baricitinib (n=7; 41.2%). In only one patient with Blau Syndrome and uveitis, tofacitinib was switched to baricitinib due to severe lymphopenia.After starting JAKINIB treatment, all patients presented clinical improvement, complete (n=15, 88.2%) or partial (n= 2; 11.8%).Based on these data a therapeutical approach of refractory IOP was proposed (Figure 1).Figure 1.Therapeutical approachConclusionJAKINIB may be an effective and safe therapy in IOP refractory to conventional or even biological immunosuppressive therapy.References[1]Meadow PB. Case Rep Rheumatol. 2014.[2]Bauermann P. Ocul Immunol Inflamm. 2019.[3]Paley MA. Am J Ophthalmol Case Reports. 2019.[4]Liu J. Ann Rheum Dis. 2020.[5]D Majumder. Indian J Ophthalmol. 2020.[6]Miserocchi E. Clin Rheumatol. 2020.[7]Pyare E. Indian J Ophtalmol, 2020.Disclosure of InterestsNone declared

Background:Ophthalmological involvement is one of the most feared manifestations of Behçet’s disease [1-6].Objectives:Our aim was to define the main demographic and clinical features of ophthalmological involvement in a well-defined cohort of patients with Behçet’s disease.Methods:Descriptive study of a cohort of 120 patients diagnosed with Behçet’s disease from January 1, 1980 to December 31, 2019. Finally, following the 2014 International Criteria for Behçet’s Disease (ICBD) (J Eur Acad Dermatol Venereol 2014; 28:338-47) 94 patients were chosen for this study.Results:50 patients (28 men/22 women; male to female ratio of 1:0.8) had ocular involvement. Mean age at diagnosis was 37.6±11.8 years. Mean ICBD score was 5.8±1.3 points. Neurological involvement was the most frequent manifestation in this group. Genital ulcers were more frequent in the non-ophthalmological involvement group. Systemic clinical domains are shown in Figure 1.The most frequent ocular manifestations were uveitis (n=44, 88.0%), retinal vasculitis (n=5, 10%) and dry eye (n=5, 10%). Likewise, the most frequent type of uveitis was anterior (n=17, 38.6%), followed by posterior uveitis (n=14, 31.8%). 26 (59.1%) of all uveitis were unilateral. Panuveitis was more frequent among patients under 60 years. Similarly, anterior uveitis was predominant in patients older than 70 years. There were no remarkable differences between genders. Main clinical features are shown in Table 1.Table 1.Clinical characteristics of ocular Behçet’s disease.n (%)Unilateral, n (%)Bilateral, n (%)Uveitis44 (88.0)26 (59.1)18 (40.9) Anterior17 (38.6)13 (76.5)4 (23.5) Intermediate2 (4.5)-2 (100) Posterior14 (31.8)9 (64.3)5 (35.7) Panuveitis11 (25.0)4 (36.4)7 (73.6)Retinal vasculitis5 (10.0)--Dry eye5 (10.0)--Cystoid macular edema4 (8.0)--Episcleritis3 (6.0)3 (100)-Optic neuritis2 (4.0)--Conclusion:Ophthalmological involvement in Behçet’s disease was more frequent in men. Uveitis and retinal vasculitis were the most frequent ocular manifestation. No remarkable differences in clinical features were observed between genders.References:[1]Atienza-Mateo B, et al. Arthritis Rheumatol. 2019; 71(12):2081-2089. doi: 10.1002/art.41026[2]Martín-Varillas JL, et al. Ophthalmology. 2018; 125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020[3]Atienza-Mateo B, et al. Rheumatology (Oxford). 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480[4]Vegas-Revenga N, et al. Am J Ophthalmol.2019;200:85-94. doi: 10.1016/j.ajo.2018.12.019[5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576[6]Santos-Gómez M, et al. Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359Figure 1.Comparison between clinical domains in patients with and without ophthalmological involvement.Disclosure of Interests:Alba Herrero-Morant: None declared, Guillermo Suárez-Amorín: None declared, Rosalía Demetrio-Pablo: None declared, Lara Sanchez-Bilbao: None declared, Carmen Álvarez-Reguera: None declared, David Martínez-López: None declared, Raúl Fernández Ramón: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, and Celgene, M. Cristina Mata-Arnaiz: None declared, Miguel Á. González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Sanofi, Lilly and MSD, Grant/research support from: AbbVie, MSD, and Roche

Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behcet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (S.D.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Background:Tocilizumab (TCZ) has shown promising results in the treatment of inflammatory ocular disease, especially in uveitis (1-3). Graves orbitopathy (GO) is the most common complication of Graves’ disease (GD). Conventional immunosuppressive drugs are not always effective or well tolerated. TCZ may be useful in the treatment of GO.Objectives:To assess the efficacy of TCZ in corticoid-resistant GO.Methods:Multicenter open study of corticoid-resistant GO. We measured clinical activity using the clinical activity score (CAS). CAS evaluates 10 different ocular items, ranging from 0 (no symptoms) to 10. We defined remission as the presence of CAS ≤ 3.Results:We studied 48 (95 eyes) patients (TABLE). Besides oral corticosteroids, they had received iv Methylprednisolone (n=43), methimazole (n=20), selenium (n=11) or radioactive iodine (n=5). According to the classification of severity (EUGOGO group), before of TCZ onset our patients had severe (n=19) or moderate (n=29) disease. TCZ was used in monotherapy (n=45) or combined with methotrexate (n=2) or azathioprine (n=1) at a dose of 8 mg/kg/iv/4 weeks (n=43) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement and most patients achieved remission (FIGURE).TABLE:Number of patients/eyes affected, n/n48/96Age, mean (SD), years50.96 (11.78)Sex, men/women, n/n (%)10/38 (20.8 / 79.2)Regimen of TCZ therapyMonotherapy/combined treatment, n (%)45/3 (93.8/6.2)• AZA1 (2.1)• MTX2 (4.2)TCZ dosage, n (%)• 8 mg/kg/iv/4 weeks43 (89.6)• 162 mg/sc/week5 (10.4)Follow-up on TCZ therapy, mean (SD), months16.05±2.06• Remission, n (%)72 (75.8)• Discontinuation treatment, n (%)29 (60.4) • Remission25 (86.2) • Inefficacy4 (13.8) • Side effects0FIGURE:After a mean follow-up of 16.1±2.1 months, most patients experienced ocular improvement, with TCZ withdrawal in 29 cases due to remission (n=25) or inefficacy (n=4). Only 5 relevant adverse events were observed (neutropenia, external otitis, otitis media, costal osteitis and gingival hyperplasia). None of these events resulted in discontinuation of the treatment.Conclusion:TCZ appears to be an effective and safe treatment in corticoid-resistant GO.References:[1] Santos-Gómez M, et al. Clin Exp Rheumatol 2016; 34 Suppl 102(6):34-40[2] Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32 (4 Suppl 84): S54-7[3] Vegas-Revenga N et al. Am J Ophthalmol. 2019 Apr; 200:85-94.Disclosure of Interests:Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martinez-Lopez: None declared, Belén Atienza-Mateo: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Vanesa Calvo-Río Grant/research support from: Abbvie, Lilly, UCB, MSD, Cellgene, Speakers bureau: Abbvie, Lilly, UCB, MSD, Cellgene, Rosalía Demetrio-Pablo: None declared, Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Iñigo González-Mazón: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, Beatriz Valls-Espinosa: None declared, Olga Maiz-Alonso: None declared, Ana Blanco Speakers bureau: Abbvie, Ignacio Torre-Salaberri: None declared, Verónica Rodriguez-Mendez: None declared, Ángel García-Aparicio: None declared, Raúl Veroz González: None declared, Vega Jovani: None declared, Diana Peiteado Grant/research support from: AbbVie, Lilly, MSD, and Roche, Speakers bureau: AbbVie, Roche, and MSD, Santos Castañeda: None declared, Margarita Sánchez-Orgaz: None declared, Eva Tomero Muriel: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Valvanera Pinillos: None declared, Elena Aurrecoechea: None declared, Ángel Mora: None declared, Arantxa Conesa: None declared, Manuel Fernández: None declared, J. Antonio Troyano: None declared, Marcelino Revenga: 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:Sarcoidosis is an inflammatory disease which can affect multiple organs. The most frequent affected organs are lungs, skin and eyes (1-5). Ocular involvement is a severe complication.Objectives:To assess the association of ocular sarcoidosis with other clinical domains.Methods:Study of a large cohort of systemic sarcoidosis from a single tertiary university hospital. All consecutive patients were diagnosed with systemic sarcoidosis from January 1, 1999 to January 1, 2019 according the ATS/ERS/WASOG criteria (6).Results:41 (22 women/19 men) of 383 (10.7%) patients had ocular involvement, mean age 44.8±16 years. Lung was the most common affected organ associated with ocular sarcoidosis (n=36; 87.8%) followed by skin (n=14; 34.1%), joints (n=12; 29.3%) and neurological affection (n=8; 19.5%).Ocular sarcoidosis presents a higher percentage of renal and neurological affection compared to organs affected in general sarcoidosis of our larger cohort (12% vs 6% and 19.5 vs 7%; respectively) (FIGURE).Conclusion:The proportion of clinical domains affected in ocular sarcoidosis is mostly similar to global sarcoidosis, except the neurological (which almost is threefold) and renal (which doubles) affection. Hence, the importance of being aware of neurological and renal complications when ocular affection is present.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8.[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32:864-8.[3]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol. 2014; 32:275-84.[4]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94.[5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32 (4 Suppl 84): S54-7.[6]Costabel U, Hunninghake GW. Eur Respir J 1999; 14: 735-737FIGURE.Comparison between distribution of organs affected in ocular sarcoidosis (left) and distribution of organs affected in general sarcoidosis (right)Disclosure of Interests:Carmen Alvarez Reguera: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Rosalía Demetrio-Pablo: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD

We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men, mean age, 34.8 &plusmn, 13.9 years). The underlying diseases were Bechet&rsquo, s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean &plusmn, SD BCVA (0.8 &plusmn, 0.3 LogMAR vs. 0.6 &plusmn, 0.3 LogMAR, p = 0.03), mean &plusmn, SD RNFL (190.5 &plusmn, 175.4 &mu, m vs. 183.4 &plusmn, 139.5 &mu, m, p = 0.02), mean &plusmn, SD MT (270.7 &plusmn, 23.2 &mu, m vs. 369.6 &plusmn, 137.4 &mu, p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10&ndash, 61.5) mg/day at baseline to. 2.5 (0&ndash, 5) mg/day after one year of follow-up, p = 0.001. After a mean &plusmn, SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.

Background Non ischaemic optic neuritis (NION) is a severe inflammation of the optic nerve that may lead to blindness. It can be primary or associated to immune mediated inflammatory diseases (IMIDs). The treatment of the NION is based on systemic corticosteroids and conventional immunosuppressive drugs. Objectives To assess the efficacy of the biological treatment in refractory NION to conventional treatment. Methods Multicenter study of 12 patients diagnosed with NION refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were visual acuity (VA) and optical coherence tomography (OCT) of the optic nerve and the ganglionar cells. Comparisons were made between baseline and the 1st week, 1st and 6th month and 1st year. (STATISTICA, StatSoft Inc. Tulsa, Oklahoma, USA). Results We studied 12 patients (19 affected eyes) (5 men/7 women); mean age of 29.8 ±12.9 years. The underlying diseases were systemic lupus erythematosus (n=1), neuromyelitis optica (n=1), neuroretinitis (n=1), relapsing polychondritis (n=1), pars planitis (n=1), Behcet’s disease (n=2) and idiopathic (n=5). Before biological treatment and besides oral corticosteroids, patients had received intravenous (IV) methylprednisolone boluses (n=9), cyclosporine A (n=1), cyclophosphamide (n=2), mycophenolate (n=2), hydroxychloroquine (n=1), methotrexate (n=8) and azathioprine (n=5). Biological treatment was bases on rituximab (n=2) (2 IV, doses of 1 g/every 2 weeks and every 6 moths), adalimumab (n=5) (40 mg/1-2 week), tocilizumab (n=4) (8 mg/kg/2-4 weeks) and infliximab (n=3) (5 mg/kg at 0, 2 and 6 week and then every 8 weeks). The characteristics of the 12 patients are shown in the TABLE. After biological treatment we observed an improvement in the ocular parameters: VA [0.66±0.32 to 0.84±0.29; p= 0.03], OCT of the optic nerve [123.20±58.28 to 190.54±175.38; p= 0.11], and OCT of the ganglionar cells [369.55±137.37 to 270.67±23.21; p= 0.03] at one year. After a mean follow-up of 29.09 ±19.23 months, there were no severe adverse effects. Conclusion Biologic therapy in NION idiopathic or associated to IMIDs, refractory to conventional treatment, seems to be effective. Disclosure of Interests D. Prieto-Pena: None declared, Monica Calderon-Goercke: None declared, Vanesa Calvo-Rio: None declared, Olga Maiz-Alonso Speakers bureau: Pfizer, Ana Blanco: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Esther Vicente: None declared, Susana Romero-Yuste: None declared, Rosalia Demetrio-Pablo: None declared, ANA URRUTICOECHEA-ARANA: None declared, Jose L. Garcia-Serrano: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Julio Sanchez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background Graves’ orbitopathy (GO) is the most common and important extrathyroidal manifestation of Graves’ disease. Corticostereoids and conventional immunosuppressors are not always effective or well tolerated. The IL-6 receptor antibody tocilizumab (TCZ) has demonstrated efficacy in the treatment of this pathology. Objectives To assess the efficacy of TCZ in refractory thyroid associated orbitopathy (TAO) due to Grave’s disease. Methods Multicenter study of 46 patients with TAO refractory to conventional immunosuppressive therapy. Results We studied 46 patients (85 eyes) (37 women/9 men); mean age at diagnosis 49.2±11.8 years. Besides oral corticosteroids, before the onset of TCZ patients had been treated with pulses of iv methylprednisolone (42), radioactive iodine (4), methotrexate (2) and other drugs (selenium in 11 cases, methimazole in 8, leflunomide in 1 and azathioprine in 1). 7 patients underwent ocular urgent decompressive surgery. According to the classification of severity of the EUGOGO group (European Group on Graves’ Orbitopathy) using the clinical activity score (CAS), before TCZ onset patients whose data were available had severe (27 eyes) or moderate (34 eyes) disease. Moreover, patients presented exophthalmos (53 eyes), strabismus (37 eyes), muscle fibrosis (38 eyes) and dysthyroid optic neuropathy (10 eyes). TCZ was used in monotherapy (43) or combined with methotrexate (2) or azathioprine (1) at 8 mg/kg/iv/4 w (41) or 162 mg/sc/w (5). TCZ yielded rapid and maintained improvement in all ocular parameters as shown in Figures. After a mean of 7.42±6.41 months using TCZ and a mean follow-up of 16.47±11.99 months, all patients experienced ocular improvement, with TCZ withdrawal in 28 cases due to complete remission (10), improvement (12) or stability of ocular inflammation (3), inefficacy (2) and total thyroidectomy (1). Only 5 relevant adverse effects were observed (neutropenia, external otitis, otitis media, costal osteitis and gingival hyperplasia, 1 each). Conclusion TCZ appears to be a useful and secure option in GO treatment. References [1] Bartalena L, et al. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid. 2008; 18 (3:333-346). [2] Russell DJ, et al. Tocilizumab as a steroid sparing agent for the treatment of Graves’ orbitopathy. Am J Ophthalmol Case Rep. 2017 Jul 8;7:146-148. Disclosure of Interests Belen Atienza-Mateo: None declared, Jose Luis Martin-Varillas: None declared, Vanesa Calvo-Rio: None declared, Rosalia Demetrio-Pablo: None declared, Elia Valls-Pascual: None declared, Beatriz Valls-Espinosa: None declared, Olga Maiz-Alonso Speakers bureau: Pfizer, Ana Blanco: None declared, Ignacio Torre-Salaberri: None declared, Veronica Rodriguez-Mendez: None declared, Angel Garcia-Aparicio: None declared, Raul Veroz Gonzalez: None declared, Vega Jovani: None declared, Diana Peiteado: None declared, Margarita Sanchez Orgaz: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Eva Tomero: None declared, Francisco J. Toyos Saenz de Miera: None declared, Valvanera Pinillos: None declared, Elena Aurrecoechea: None declared, Angel Mora: None declared, Arantxa Conesa: None declared, Manuel Fernandez: None declared, J. Antonio Troyano: None declared, Inigo Gonzalez-Mazon: None declared, Lara Sanchez Bilbao: None declared, D. Prieto-Pena: None declared, Monica Calderon-Goercke: None declared, Miguel A. Gonzalez-Gay: None declared, Ricardo Blanco: None declared

Background: Sarcoidosis is a multisystemic inflammatory disease characterized by non-caseating epitheliod granulomas that can affect any organ system. The three most frequency affected organs are lung, skin and eyes. Ocular involvement is the presenting symptom in approximately 20-30% and can involve any part of the eye and its anexal tissues. Sarcoidosis may cause uveitis, conjunctivitis, episcleritis/scleritis, optical nerve disease and orbital inflammation. Objectives: To analyze the prevalence of ocular involvement is systemic sarcoidosis, the clinical patterns and their correlation with the International Workshop on Ocular Sarcoidosis (IWOS) criteria. These criteria classify ocular sarcoidosis as definite, presumed, probable and possible, according to some ophthalmological and analytical findings. They are especially useful if a biopsy is not obtained or it is negative. Methods: Retrospective study of patients admitted to a single reference University Hospital between 1999 and 2019 with diagnosis of sarcoidosis. Clinical findings, demographics features, anatomic location and IWOS intraocular signs were recorded. We also collected serum angiotensin converting enzyme (ACE), liver enzyme test, chest radiography, chest computed tomography scan, treatment and biopsy if performed. Results: We selected patients with ocular inflammation from a cohort of 381 patients with sarcoidosis (n=50, 13%). Most of the cases were women (54%) and median age was 45.5±16.7 years. In these 50 cases, the most affected organ was lung (60%), followed by skin (28%). Forty patients had uveitis, 32 of them with ocular symptoms. Thirty-nine out of 50 patients (78%) met one of the 4 IWOS diagnostic categories: 22 with definite (44%), 13 presumed (26%) and 4 with possible (8%) sarcoidosis. Eleven patients did not meet IWOS criteria. The most common ocular signs were bilaterality (44%), snowballs or strings of pearls (38%), mutton-fat KPs (24%), multiple chorioretinal peripheral lesions (14%) and periphlebitis (10%). The median value of ACE was 69 U/l. Forty-four patients (88%) received oral corticosteroids, 21 (42%) received methotrexate, 11 (21%) received another conventional immunosuppressor and 11 (21%) a biological treatment. TABLE shows demographic and clinical features. Conclusion: In our population the IWOS Criteria had a sensitivity of 78%. Even though there is no gold standard for diagnosing ocular sarcoidosis yet, IWOS signs can help clinicians suspect it. References: [1] Herbort CP, Rao NA, Mochizuki M; members of Scientific Committee of First International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop On Ocular Sarcoidosis (IWOS). Ocul Immunol Inflamm. 2009May-Jun;17(3):160-9. Disclosure of Interests: None declared

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

Background Sarcoidosis is a systemic granulomatous disease characterized by the presence of non-necrotizing granulomas in different parenchyma. Objectives To describe demographic, clinical and analytical features in a cohort of patients with Sarcoidosis diagnosis from northern Spain during the last twenty years. Methods Descriptive study of 381 patients diagnosed with sarcoidosis during the period 01/01/1999 to 01/01/2019. Biopsy and/or clinical and compatible imaging tests were required for the diagnosis of sarcoidosis. Demographic parameters, clinical manifestations, complementary tests and treatment were registered. Results are expressed as mean±SD or as median and interquartile range (IQR) as appropriate. Results 381 patients (192 female/191 male, ratio 1:1), with a mean age 45.5±15.4 years at disease onset, and with 94.8% of Spanish nationality. 33% were smokers at diagnosis and 6.3% had tuberculosis (Table 1). The sarcoidosis incidence rate in our population was 3.3 cases/100000 p/year, similar to other national series1. Most frequent clinical manifestations were as follow: pulmonary symptoms (72.3%), general symptoms (37.3%), skin involvement (31%), joint manifestations (27.9%), ophthalmological manifestations (13.0%), digestive disorders (9.3%), neurological symptoms (6.5%), nephrological (4.7%) and cardiological involvement (1.6%) (Table 1). In addition, 11.5% of the patients had a Lofgren syndrome, 0.5% a Heerdfort syndrome and up to 11.5% had mediastinal adenopathy as an incidental finding in simple chest radiography. A simple chest radiograph was performed in all patients. 83.7% presented abnormal patterns: stage I (41.4%), stage II (32%), stage III (7.6%) and stage IV (3.8%). In addition, 29.9% and 10.5% of patients presented pathological scintigraphy and PET respectively. Biopsy was performed in 81.9%, with a mediastinal approach in 43.3%. (Table 2). After a median follow-up of 11.0 [6.0-17.0] years, we observed that up to 32% of patients never received treatment. In the remaining 68%, the main treatment was oral glucocorticoids with a mean dose of 43.4±19.1 mg/day. Other treatments used were conventional immunosuppressants and biological agents (table 2). Conclusion Results obtained were similar to other national and international series, with the exception of non-predominance of female sex and the highest percentage of ocular involvement in our study. Currently, biological treatment (especially anti-TNF-alpha) is used more frequently. References [1] Manaet al. Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: Cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore). 2017Jul;96(29):e7595. Disclosure of Interests Jose Luis Martin-Varillas: None declared, Lara Sanchez Bilbao: None declared, Inigo Gonzalez-Mazon: None declared, Raul Fernandez Ramon: None declared, D. Prieto-Pena: None declared, David Martinez-Lopez: None declared, Eva Pena Sainz-Pardo: None declared, Belen Atienza-Mateo: None declared, Monica Calderon-Goercke: None declared, Rosalia Demetrio-Pablo: None declared, Vanesa Calvo-Rio: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background Immune checkpoint blockade therapy (ICBT) currently is one of the most used therapies against cancer. The activation of the immune system can lead to different immune-related adverse events (irAEs), being the rheumatological side effects among the most common. Objectives Our aim was to assess the rheumatological irAEs in patients who received immunotherapy. Methods We set up an observational study of patients treated with Nivolumab and Pembrolizumab (anti-PD1), Atezolizumab (anti-PD-L1) and Ipilimumab (antiCTLA-4) for solid organ tumors. All these patients were followed in a single reference University Hospital from March-2015 up to December-2018. The main outcome was to determinate the incidence of rheumatological irAEs. Results We studied 102 patients (63♂/39♀) with a mean age of 60.6±9.7 with different solid organ tumors. Only 7 patients (6.8%) had a previous diagnosis of an immune-mediated disease: psoriasis (n=2), psoriatic arthritis (1), systemic lupus erythematosus (1), spondyloarthitis (1), rheumatoid arthritis (1) and skin lupus (1). Rheumatological side effects were observed in 15 patients (14.7%): inflammatory arthralgia (8), arthritis (6), myositis (2) and aortitis (1). The time of appearance of the rheumatological irAEs was of 6.36 months (±5.81). From the 7 patients with previous diagnosis of an immune-mediated disease, only 1 patient with psoriasis suffered a worsening of skin symptoms and another one with psoriatic arthritis had a monoarthritis episode. Among the 14 patients who suffered from arthralgia/arthritis, the most frequent pattern was oligoarticular (40%), followed by poly (30%) and monoarticular (30%). The most affected joint was the knee (n=4), followed by wrist (3), hands (3), ankle (2), shoulder (2) and foot (1). Apart from the articular disease, 2 patients suffered from myositis in lower limbs, with weakness of legs and arthralgia in their knees. A patient was diagnosed of aortitis through a PET, although the patient did not have any symptom. Immunology tests with RF, ACCP and ANA were done in 8 out of the 15 patients with musculoskeletal irAEs, being negative in all cases. Interviewing 40 of the patients who received ICBT, 7 of them (17.5%) referred xerophthalmia. 6 of them (15%) had a positive Schrimer test, and 3 (7.5%) had a reduced tear break-up time. None patient met Sjogren criteria. In 6 out of the 15 patients with rheumatological irAEs (all of them with arthralgia/arthritis) the ICBT was removed, temporary in all cases, and could be reintroduced after a mean of 33 ± 18.9 days. 6 patients were treated with NSAIDs and 5 with oral prednisone (2 of them also required intra-articular corticoids). Conclusion Rheumatological irAEs are common in clinical practice. Arthralgia-Arthritis and dry-syndrome are the most frequent adverse events. Disclosure of Interests Lara Sanchez Bilbao: None declared, Inigo Gonzalez-Mazon: None declared, Rosalia Demetrio-Pablo: None declared, Jose Luis Martin-Varillas: None declared, Marina Delgado Ruiz: None declared, Isabel Bernat Pina: None declared, Belen Atienza-Mateo: None declared, Monica Calderon-Goercke: None declared, D. Prieto-Pena: None declared, Almudena Garcia Castano: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen DOI: 10.1136/annrheumdis-2019-eular.7386

Background Ocular involvement in Behcet’s disease (BD) is a potential severe and disabling complication. Anti-TNF-α agents have shown an improvement of visual outcome in BD-related uveitis refractory to conventional immunosuppressive (IS) drugs. However, these drugs do not achieve control of intraocular inflammation in all patients or are not well tolerated. Tocilizumab (TCZ) has shown efficacy in different refractory ocular inflammatory diseases. Objectives To assess the efficacy of long-term therapy with TCZ in refractory uveitis associated to extraocular manifestations (EOM) due to BD. Methods Multicenter study of patients with BD refractory to standard systemic treatment. Results We followed up 14 patients (9 men/5 women) (26 affected eyes); mean age 40.8±19.5 years. Pattern of ocular involvement: panuveitis (10; 4 with retinal vasculitis), anterior (3) and posterior (1) uveitis; 8 recurrent and 6 chronic; 9 with cystoid macular edema. At TCZ onset the following EOM were present: oral and/or genital ulcers (10), arthritis (6), folliculitis/pseudofolliculitis (6), erythema nodosum (3), livedo reticularis (1), intestinal affection (1) and neurological involvement (3). Before TCZ, they had received corticosteroids (13 intraocular, 12 oral and 12 iv), conventional IS drugs and biologic agents: methotrexate (11), cyclosporine (8), azathioprine (10), colchicine (1), cyclophosphamide (2), mycophenolate mofetil (1), adalimumab (10), infliximab (6), golimumab (3), canakinumab (1), or etanercept (1). TCZ was used in monotherapy (7) or combined with conventional IS drugs (7) at 8 mg/kg/iv/4 w (11) or 162 mg/sc/w (3). After a mean follow-up of 21.7±14.5 months using TCZ, all patients experienced ocular improvement, with complete remission in 10. However, TCZ was only effective in 5 of the patients with EOM. TABLE shows the evolution of ocular parameters. TCZ had to be withdrawn temporally in 1 case, due to an episode of cellulitis with sepsis, and definitely in 4 cases, due to a severe infusion reaction, arthritis impairment, persistence of oral ulcers or a new episode of uveitis (1 each). Prednisone dose was significantly reduced until suspension in all patients. Conclusion TCZ seams a useful and secure therapy in highly refractory BD-related uveitis. References [1] Atienza-Mateo B, Calvo-Rio V, Beltran E, et al. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcet’s disease: multicentre retrospective study. Rheumatology (Oxford). 2018 May 1;57(5):856-864. [2] Calvo-Rio V, de la Hera D, Beltran-Catalan E, et al. Tocilizumab in uveitis refractory to other biologic drugs: a study of 3 cases and a literature review. Clin Exp Rheumatol.2014; 32(4 Suppl 84): S54-7. Disclosure of Interests Belen Atienza-Mateo: None declared, Jose Luis Martin-Varillas: None declared, Vanesa Calvo-Rio: None declared, Rosalia Demetrio-Pablo: None declared, Natalia Palmou-Fontana: None declared, J. Loricera: None declared, Emma Beltran: None declared, Marisa Hernandez-Garfella: None declared, Lucia Martinez-Costa: None declared, Elia Valls-Pascual: None declared, Antonio Atanes-Sandoval: None declared, Miguel Cordero-Coma: None declared, Joan Miquel Nolla: None declared, Carmen Carrasco-Cubero: None declared, Julio Sanchez: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Lara Sanchez Bilbao: None declared, Inigo Gonzalez-Mazon: None declared, Monica Calderon-Goercke: None declared, D. Prieto-Pena: None declared, Miguel A. Gonzalez-Gay: None declared, Ricardo Blanco: None declared

Background:Rapid and effective remission-inducing therapy is mandatory in uveitis to avoid irreversible structural and functional damage. In some severe cases biological agents might be required (1-6).High-dose intravenous methylprednisolone (IVMP) may achieve prompt control of inflammation in most immune mediated inflammatory diseases (IMID), including non-infectious uveitis (NIU).Objectives:To evaluate the efficacy and safety of IVMP pulse therapy in NIU of different IMID.Methods:Multicentre study of 71 patients with severe uveitis who received IVMP. The underlying diseases were: Vogt Koyanagy Harada disease (VKHD) (n=24), Behçet disease (BD) (19), Sarcoidosis (5) and idiopathic NIU (23). The main outcome variable was Best-Corrected Visual Acuity (BCVA) estimated using the Snellen chart. BCVA that was assessed at 0 (basal), 2-5, 7, 15 and 30 days after IVMP.The results are expressed as mean ±SD in normally distributed variables, or as median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test.Results:We studied 46♀/ 25♂ patients. The main features are shown in Table 1. IVMP dose ranged from 250 to 1000 mg/day administered for 3-5 consecutive days, the dose was established according to the presence or not of other systemic manifestations apart from uveitis. All of them had active intraocular inflammation at the moment of the study. BCVA values improved considerably after 1 month (Figure 1). No major side effects were observed.Figure 1.Improvement of best corrected visual acuity (BCVA).Conclusion:High-dose IVMP pulse therapy is useful and safe for a prompt control of BCVA regardless of the underlying IMID.References:[1]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576[3]Santos-Gómez M, et al. Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359[4]Atienza-Mateo B, et al. Rheumatology (Oxford) 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480.[5]Atienza-Mateo B, et al. Arthritis Rheumatol. 2019; 71(12):2081-2089. doi: 10.1002/art.41026.[6]Martín-Varillas JL, et al. Ophthalmology. 2018;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020Table 1.Main features of 71 patients with NIU. Data are of affected eyes.VKHD(n=24)Idiophatic(n=23)Behcet’s disease (n=19)Sarcoidosis(n=5)Overall(n=71)Men/Women, n5/199/149/102/371Mean age (years) ±SD42 ±1147 ± 1533±1042 ± 22-Unilateral/Bilateral NIU, n (%)2 (8.3)/22(91.7)10 (43.5)/13(56.5)4 (21)/15 (79)3(60)/2(40)19/52NIU patterns, n (%) Posterior uveitis6 (25)9 (39.1)3 (15.8)1 (20)19 Panuveitis18 (75)14 (60.9)16 (84.2)4 (80)52Laboratory data, n (%) ANA2 (8.34)2 (8.7)0 (0)1 (20)5 HLA B270 (0)4 (17.4)0 (0)0 (0)4 HLA B290 (0)1 (4.3)0 (0)0 (0)1 HLA B510 (0)5 (21.7)8 (42)3 (60)16 Angiotensin Converting Enzyme (ACE)1 (4.17)2 (8.7)0 (0)1 (20)4Disclosure of Interests:None declared

Background:Sarcoidosis is a systemic and potentially severe disease (1). Its incidence varies widely worldwide.Objectives:The aim of this study was to estimate the sarcoidosis incidence in a Northern Spanish population-based cohort.Methods:All incident cases of sarcoidosis between January 1999 and December 2019 in a tertiary hospital were reviewed. Inclusion criteria were a) diagnosis of sarcoidosis according to ATS/ERS/WASOG (Eur Respir J. 1999; 14:735-7) and b) patients residing in our health region. Incidence between 1999 and 2019 was estimated by sex, age, and year of diagnosis.Results:From a total of 384 patients diagnosed with sarcoidosis, 234 (129 women/ 105 men) met the inclusion criteria and were finally included in the study. Mean age of the cohort at diagnosis was 48.43±14.83 years (46.95±14.50 in males; 49.63±15.04 in females, p=0.12). Annual incidence during 1999-2019 period was 3.56 per 100,000 population (3.32 per 100,000 in males and 3.72 per 100,000 in females). An upward trend in annual incidence over time was observed with rates ranging from 1.73 per 100,000 inhabitants in 1999 to 6.91 per 100,000 inhabitants in 2016 (Figure 1). Overall, sarcoidosis was predominantly diagnosed during middle adulthood. A bimodal distribution of age-specific incidence rates was observed in both sexes with two peaks in the age groups of 30-39 (4.98 per 100,000) and 60-69 years (5.12 per 100,000) in men, and in 40-49 (6.45 per 100,000) and 60-69 years (5.94 per 100,000) in women.Comparative studies with other regions are summarize in Table 1.Conclusion:A progressive increase in incident sarcoidosis is observed. The estimated incidence of sarcoidosis in this study (3.56 per 100,000) was like that of other Mediterranean countries (2). No gender predominance was observed. Demographics variations, changes in practice patters or diagnostic test improvements could explain the upward trend in sarcoidosis incidence detected in our study. Consistent with previous studies, male presented an incidence peak 10 years earlier than female (3-5).References:[1]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol 2014; 32(2): 275-84. PMID: 24321604[2]Brito-Zerón P, et al. Clin Exp Rheumatol. 2019;37(6):1052–64.[3]Arkema E V., et al. Eur Respir J. 2016;48(6):1690-9.[4]Yoon H, et al. Am J Respir Crit Care Med. 2018;197(MeetingAbstracts):1-8.[5]Ungprasert P, et. Mayo Clin Proc. 2016 Feb;91(2):183-8.Figure 1.Annual incidence of sarcoidosis in 1999-2019 (A)Table 1.Sarcoidosis incidence rates reported in the literature.Study, yearCountry, data sourceTime periodIncident casesIncidence per 100,000 persons-yearPietinalho, 1995Finland, hospital database19841,37811.4Pietinalho, 1995Japan, Hokkaido, hospital database19842881.0Yigla, 2002Israel, hospital database1980-19961200.8Byg, 2003Denmark, Danish National Patient Registry1980-19945,5367.2Gribbin, 2006UK, Health Improvement Network1990-20031,0195.0Gillman, 2007Australia, Victoria, hospital database1995-20051224.4-6.3Haraldsdottir, 2007Iceland, hospital database1981-20032353.8Musellin, 2009Turkey, healthcare providers2004-20062934.0Deubelbeiss, 2010Switzerland, Swiss Federal Office for Statistics2002-20052,9257.0Kowalska, 2014Poland, Katowice, National Health Fund2006-20101,2173.8-4.5Arkema, 2016Sweden, National Patient Register2003-201310,78710.4-14.8Baughman, 2016USA, Optum Health Care Database2010-201329,372African American: 17.8; Caucasian: 8.1; Hispanic: 4.3; Asian: 3.2Duchemann, 2017France, Seine-Saint-Denise County20123614.9Škopljanac, 2017Croatia, Split- Dalmatia County, hospital database1986-20153183.1-3.4Yoon, 2018Korea, National Health Insurance2007-20164,7910.85Fidler, 2019Canada, Ontario, health administrative data1996-201518,5506.8-7.9Fernandez, 2011Spain, Leon, hospital database2001-20081184.51Present study, 2020Spain, Santander, hospital database1999-20192343.56Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Raúl Fernández-Ramón: None declared, Jorge Javier Gaitán-Valdizán: None declared, José Luis Martín-Varillas: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Rosalía Demetrio-Pablo: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

Background:Ocular scleral pathology (OSP) includes episcleritis and scleritis. Episcleritis is generally a benign disease with a self-limited course, while scleritis is a more severe ocular condition. In some severe and refractory cases systemic therapy may be required.Objectives:In a wide series with OSP our aim was to assess a) underlying diseases and b) systemic treatment.Methods:Study of unselected all consecutive patients studied in a single University Hospital during the last ten years with: a) episcleritis and b) scleritis diagnosed by clinical features and slit-lamp (Watson and Hayreh criteria). Best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured at diagnosis and after systemic treatment.Results:We studied 175 patients (106 women/ 69 men) /212 affected eyes with OSP (episcleritis=135; scleritis=40); mean age 48.9±14.2 years.OSP was unilateral in 138 (78.9%), recurrent in 74 (42.9%) and chronic in 21 (12%). Most of them were idiopathic (n=81, 46.3%) while associated with IMID were 43.4% (Table 1). The most important underlying IMID were spondyloarthritis and inflammatory bowel disease, without significant differences between scleritis and episcleritis. Granulomatosis with polyangiits and systemic lupus erythematosus were more frequent in scleritis, not reaching statistical significance.Regarding treatment, topical treatment was used in all patients. 41.1% received systemic treatment, including systemic glucocorticoids, cDMARDS and bDMARDs. Systemic glucocorticoids and Methotrexate were used more frequently in scleritis (Table 1). The main indication for biologic therapy was related to underlying IMID in both groups, but 7 bDMARDs in scleritis were indicated for systemic and ocular compromise.BVCA and IOP improved significantly after systemic treatment in scleritis (Figure 1).Figure 1.BVCA and IOP at diagnosis and last visit.Conclusion:OSP is a relatively frequent entity. It is necessary to exclude an underlying systemic disease to establish correct systemic treatment.Table 1.Underlying diseases and systemic treatment.Overall(n =175)Episcleritis(n=135)Scleritis(n=40)pAge (years), mean ± SD48.9 ± 14.247.8 ± 14.352.6 ± 13.90.061Sex (women), n (%)106 (60.6)81 (60)25 (62.5)0.920UNDERLYING DISEASE-Idiopathic, n (%)81 (46.3)65 (48.1)16 (40)0.364-Infectious, n (%)11 (6.3)7 (5.2)4 (10)0.276-IMID, n (%)76 (43.4)57 (42.2)19 (47.5)0.563∘Spondyloarthritis21 (12)17 (12.6)4 (10)0.787∘Crohn’s disease16 (9.1)14 (10.4)2 (5)0.469∘Rheumatoid Arthritis14 (8)12 (8.9)2 (5)0.740∘Granulomatosis with polyangiits7 (4)3 (2.2)4 (10)0.080∘Relapsing polychondritis6 (3.4)4 (3)2 (5)0.621∘Systemic lupus erythematosus5 (2.9)2 (1.5)3 (7.5)0.079∘Ulcerative colitis3 (1.7)2 (1.5)1 (2.5)0.796SYSTEMIC TREATMENT72 (41.1)37 (27.4)35 (87.5)0.000*-Systemic glucocorticoids, n (%)72 (41.1)37 (27.4)35 (87.5)0.000*-Methotrexate, n (%)39 (22.3)17 (12.6)22 (55)0.000*-Non-methotrexatecDMARD, n (%)35 (20)24 (17.8)11 (27.5)0.177-TNFibDMARD, n (%)27 (15.4)19 (14.1)8 (20)0.362-Non-TNFibDMARD, n (%)8 (4.6)5 (3.7)3 (7.5)0.386*p*pDisclosure of Interests:Lara Sanchez-Bilbao: None declared, Vanesa Calvo-Río Speakers bureau: AbbVie, Lilly, Celgene, Grünenthal and UCB Pharma., Grant/research support from: MSD and Roche, José Luis Martín-Varillas: None declared, Carmen Álvarez-Reguera: None declared, Alba Herrero-Morant: None declared, Iñigo González-Mazón: None declared, Rosalía Demetrio-Pablo: None declared, Miguel A González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Celgene and MSD. Ricardo, Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: AbbVie, MSD and Roche

Background:Ocular involvement in sarcoidosis can be present in up to 80% of patients. If not treated, it can lead to significant visually complications (1-5).Objectives:Our aim was to assess the main a) epidemiology and b) clinical features of ocular sarcoidosis in a wide and unselected series from a single university hospital.Methods:Study of a large cohort (n=384) of all consecutive patients diagnosed with sarcoidosis from January 1, 1999 to December 31, 2019. Finally, 344 patients were included according to the ATS/ERS/WASOG criteria (Eur Respir J. 1999;14:735-7).Results:65 (33 men/32 women) of 344 (18.9%) patients had ocular involvement. Mean age at diagnosis was 45.6±15.9 years. The most frequent extraocular clinical clusters were respiratory (80%), osteoarticular (30.8%) and cutaneous (29.2%) (figure 1). Ocular manifestations and complications are shown in table 1. Uveitis (83.1%), orbital lesions (7.7%) and retinal vasculitis (6.2%) were the most common ocular lesions. Median Best Corrected Visual Acuity (BCVA) at diagnosis and after one year of follow-up was 0.6 [0.3-0.8] and 0.9 [0.30-1], respectively. Retinal vasculitis was associated to the worst BCVA outcome, and panuveitis to more frequent and severe complications.Conclusion:Ocular manifestations, especially uveitis, are frequent in sarcoidosis. A more aggressive and early treatment may be indicated in panuveitis and retinal vasculitis.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum 2015;45:361-8.[2]Riancho-Zarrabeitia L et al. Clin Exp Rheumatol 2014; 32:275-84.[3]Vegas-Revenga N, et al. Am J Ophthalmol 2019; 200:85-94.[4]Calvo-Río V, et al. Clin Exp Rheumatol 2014; 32 (4 Suppl 84): S54-7. Epub 2014 Jul 8.[5]Cordero-Coma et al. Mediators Inflamm. 2014; 2014:717598.Figure 1.Clinical clusters of associations in ocular sarcoidosis.Table 1.Ocular manifestations and associated complications after 1 year of follow-up of 65 patients with ocular sarcoidosis.Type of ocular affectationN (%)Median BCVA at onset[IQR]Median BCVA after 1 year of follow-up[IQR]CataractN (%)OPN (%)OHTN (%)CMEN (%)ERMN (%)Uveitis, pattern54 (83.1)0.6 [0.3-0.8]0.9 [0.6-1]18 (27.7)11 (16.9)7 (10.8)7 (10.8)8 (12.3)Anterior31 (47.7)0.7 [0.3-0.8]0.8 [0.5-1]13 (41.9)2 (6.5)2 (6.5)2 (6.5)2 (6.5)Panuveitis16 (24.6)0.4 [0.2-0.7]0.9 [0.5-1]5 (31.3)7 (43.8)4 (25)5 (31.3)5 (31.3)Posterior5 (5.2)0.5 [0.1-0.9]0.9 [0.9-1]02 (40)1 (20)00Intermediate2 (3.1)0.50.700001Orbitary lesions5 (7.7)0.5 [0.1-0.6]1 [0.1-1]1 (20)01 (20)00Retinal vasculitis4 (6.2)0.6 [0.5-0.8]1 [0.6-1]00001 (25)Dry eye4 (6.2)10.900000Scleritis10.61.000000Abbreviations: BCVA: Best corrected visual acuity; CME: Cystoid macular edema ERM: Epiretinal membrane; OP: Optic Papillitis; OHT: Ocular hypertension.Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Rosalía Demetrio-Pablo: None declared, José Luis Martín-Varillas: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myer, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

Background:Ocular involvement is a relatively frequent and potentially severe complication of sarcoidosis. Oral corticosteroids (OCS) are the first-line treatment. Conventional immunosuppressive agents (cIS) and biological therapy (BT) can be used in refractory cases (1-5).Objectives:To evaluate the treatment and visual outcomes of a cohort of patients diagnosed with ocular sarcoidosis.Methods:Study of a large cohort (n=384) of all consecutive patients diagnosed with sarcoidosis from January 1, 1999 to December 31, 2019 at a single University Hospital. Finally, 344 patients were included according the ATS/ERS/WASOG criteria (Eur Respir J. 1999; 14:735-7). Different ocular manifestations and the following systemic treatments were assessed: a) OCS, b) cIS), c) monoclonal TNF inhibitors, d) Etanercept (ETN), e) Tocilizumab (TCZ). Best Corrected Visual Acuity (BCVA) according to different systemic treatments was compared at diagnosis and after one year of follow-up (Kruskall Wallis test).Results:344 patients were reviewed. From these, 65 (18.9%) presented ocular manifestations as uveitis (83.1%), orbital lesions (7.7%), retinal vasculitis (6.2%), dry eye (6.2%) and scleritis (1.5%). All of them received systemic treatment. BT was particularly used in patients with retinal vasculitis (100%), panuveitis (75%) and orbital lesions (40%). Systemic treatment and BCVA outcome according to ocular manifestations are shown in table. Median BCVA at onset and after one year was 0.6 [interquartile range (IQR) 0.3-0.8] and 0.9 [0.6-1], respectively. No statistically significant differences were observed between systemic treatments in BCVA of patients with uveitis after 1 year of follow-up (Figure).Figure 1.Median [25,75 IQR] BVCA after one year follow up according to type of systemic treatment in sarcoid uveitis.Median BCVA after one year Systemic treatmentAbbreviations: BCVA: Best Corrected Visual Acuity; OCS: Oral Corticosteroids; Conventional IS: Conventional immunosupressants; Monoclonal TNFi: monoclonal tumour necrosis factor inhibitors; ETN: Etanercept; TCZ: Tocilizumab.Conclusion:Panuveitis, intermediate uveitis and orbital lesions, require a more aggressive treatment than other manifestations of ocular sarcoidosis. In uveitis, an important improvement in BCVA after 1 year of follow-up was observed regardless of the type of treatment used.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum 2015;45(3):361-8. PMID: 26092330[2]Riancho-Zarrabeitia L et al. Clin Exp Rheumatol 2014;32(2):275-84. PMID: 24321604[3]Vegas-Revenga N, et al. Am J Ophthalmol 2019; 200:85-94. PMID: 30660771[4]Cordero-Coma et al. Mediators Inflamm 2014; 2014:717598. PMID: 24976689[5]Calvo-Río V, et al. Clin Exp Rheumatol 2014; 32 (4 Suppl 84): S54-7. PMID: 25005576Table 1.Median BCVA at onset and after one year according to ocular manifestations and type of systemic therapy.Type of ocular affectationn (%)Median BCVA at onset [IQR]Median BCVA after 1 year [IQR]OCSn (%)cISn (%)monoclonal TNFin (%)ETNn (%)TCZn (%)Uveitis54 (83.1)0.6 [0.3-0.8]0.9 [0.6-1]44 (81.5)29 (53.7)16 (29.6)3 (5.5)3 (5.5) -Anterior31 (47.7)0.7 [0.3-0.8]0.8 [0.5-1]22 (70.9)12 (38.7)2 (6.5)2 (6.5)0 -Intermediate2 (3.1)0.50.72 (100)1 (50)1 (50)1 (50)1 (50) -Posterior5 (5.2)0.5 [0.1-0.9]0.9 [0.9-1]4 (80)4 (80)3 (60)00 -Panuveitis16 (24.6)0.4 [0.2-0.7]0.9 [0.5-1]16 (100)12 (75)10 (62.5)02 (12.5)Orbital lesions5 (7.7)0.5 [0.1-0.6]1 [0.1-1]4 (80)2 (40)2 (40)01 (20)Retinal vasculitis4 (6.2)0.6 [0.5-0.8]1 [0.6-1]4 (100)4 (100)1 (25)01 (25)Dry eye4 (6.2)10.92 (50)1 (25)000Scleritis1 (1.5)111 (100)0000Abbreviations: BCVA: Best Corrected Visual Acuity; IQR: Interquartile Range; OCS: Oral Corticosteroid; cIS: Conventional Immunosuppressants; Monoclonal TNFi: monoclonal tumour necrosis factor inhibitors; ETN: Etanercept; TCZ: Tocilizumab.Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Rosalía Demetrio-Pablo: None declared, José Luis Martín-Varillas: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

Background:Anterior uveitis (AU) is one of the most frequent extra articular manifestations of axial spondyloarthritis (axSpA), present in around 25% of patients. As with axSpA, AU has also been associated with the development of accelerated atherosclerosis1. If the presence of AU confers an increased cardiovascular (CV) risk or specific disease-related features to patients with axSpA remains unclear.Objectives:To compare the atherosclerotic burden, CV events, CV risk factors and disease related factors including structural damage in axSpA patients with and without AU.Methods:Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA, comparing axSpA patients with and without concomitant uveitis. Background information on CV and disease-related factors was reviewed. Data on CV risk and disease status at the time of the study were also obtained, including the structural damage assessed by the presence of syndesmophytes, the severity of the sacroiliitis (defined as grade 3 or 4 according to New York criteria), and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria.Results:A set of 886 axSpA patients were included. 709 (80.0%) of them had no history of concomitant AU, which was present in the remaining 177 (20.0%). The group with AU was older (50 ± 11 vs 48 ± 13 years, p=0.05), had a higher proportion of patients with AS (90.1% vs 76.3%, p=0.00) (Table 1) and a longer disease duration 13(7-23) vs 7(2-16) years, p=0.00]. The prevalence of HLA-B27 was higher in AU patients (82% vs 67%).Remarkably, structural damage showed interesting differences between both groups (Table 1). AU patients had a higher prevalence of severe sacroiliits (69% vs 49%, p=0.00), which remained significant after adjustment for age, disease duration and AS/nr-axSpA ratio. Furthermore, a non-significant trend towards a higher prevalence of syndesmophytes (44% vs 36%, p=0.06) and hip involvement (20% vs 15%, p=0.09) was observed in the group of AU.Regarding CV risk features, no differences were observed in the prevalence of CV risk factors and events (Table 1). Patients with AU showed a higher cIMT in the crude analysis (665 ± 156 mm vs 640 ± 142 mm, p = 0.047), but no significant differences were observed after adjustment by age and sex (p=0.6). Prevalence of carotid plaques was comparable in both groups (32% Vs 32%, p=0.84).Table 1.axSpA without uveitis (n=709)axSpA with uveitis (n=177)pP (adjusted model)Men/Women, n477/232122/550.68Mean age (years) ±SD at the time of study48 ± 1350 ± 110.049AS/nr-AxSpa541/168160/170.000History of CV risk factors, n (%) Current smoker247 (35)50 (28)0.096 Obesitty Dyslipemia233 (33)63 (36)0.48 Hypertension188 (27)50 (28)0.63 Diabetes Mellitus50 (7)14 (8)0.69 Chronic Kidney Disease18 (3)4 (2)0.99History of cardiovascular events, n (%)29 (4)12 (7)0.13Structural damage at the time of studyPresence of syndesmophytes, n (%)253 (36)77 (44)0.063mSASSS5 (1-15)6 (0-16)0.31Severe sacroiliitis (grade 3,4), n (%)348 (49)122 (69)0.0000.000*Carotid US data at the time of studyCarotid plaques, n (%)225 (32)57 (32)0.84IMT (mm)640 ± 142665 ± 1560.0470.6**IMT >= 0.900 mm36 (5)10 (6)0.72*: adjusted by age, disease duration and AS/nr-axSpA ratio**: adjusted by age and sexAbbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis.Conclusion:The presence of AU does not confer additional CV risk to axSpA patients, although it is associated with a more severe structural damage in our series.References:[1]Conkar S, Güven Yilmaz S, Koska İÖ, Berdeli A, Mir S. Evaluation of development of subclinical atherosclerosis in children with uveitis. Clin Rheumatol. 2018 May;37(5):1305-1308.Disclosure of Interests:None declared

Background:Behçet disease (BD) is a systemic and potentially severe disease. Its incidence varies widely worldwide. In Spain, published BD’s epidemiological studies are scarce.Objectives:In a well-defined Northern Spanish population-based cohort, the aim of this study was a) to estimate epidemiological variations, b) clinical domains and c) to compare our results with other regions.Methods:Study of unselected all consecutive patients diagnosed with definitive or possible BD by expert rheumatologists between 1980 and 2020 in our health region. Two classification criteria were applied: a) International Study Group (ISG) for BD [1], and b) International Criteria for BD (ICBD) [2]. In addition, a literature review of Medline publications was carried out.Results:In this study, from a total of 120 patients diagnosed with BD by expert opinion (58 women/62 men), 96 met ICBD and 59 ISG criteria. Mean age of the cohort at diagnosis was 37.6±13.8 years similar to other countries, as well as sex distribution.Prevalence was higher than in most European populations regardless the diagnostic criteria applied: expert opinion (20.6), ICBD (16.5) or ISG (10.1) (TABLE 1). Incidence was lower (expert opinion: 0.022, ICBD: 0.018, ISG: 0.011). Clinical domains’ frequency was in line with other regions except vascular and gastrointestinal involvement, which were lower.TABLE 1.Diagnostic criteria and study periodn cases / population sizeMean age at onset and sex (%female)Prevalence (over 100000) / incidenceOral / genital ulcers (%)Skin lessions/ pathergy test (%)Ocular involve ment (%)Joint involve ment (%)Neurobehcet/ Vascular/ Gastrointestinalinvolvement (%)Sánchez. L et al. Southern Europe (Cantabria, Spain)Expert opinion, ISG, ICBD / 1980- 2020120 (expert opinion) / 96 (ICBD) / 59 (ISG) / 58164137.6 ±13.8/ 48.320.6 (expert opinion), 16.5 (ICBD), 10.1 (ISG) / 0.022 (expert opinion), 0.018 (ICBD), 0.011 (ISG)94.2 / 59.263.3 / 25. 241.66510.8 / 11.6 / 6.6Calamia, K. T. et al. North America (Minnesota, USA)ISG / 1960-200513 / NR31 / 305.2 / 0.38100 / 6285 / NR624623 / 23 / NRAltenburg, A. et al. Northern Europe (Berlin, Germany)ISG and ABD classification tree / 1961-2005590 / 339134426 / 584.9 / 1 (estimated)98.5 / 63.762.5 / 33.758.15310.9 / 22.7 / 11.6Mohammad, A. et al. Northern Europe (Skane County, Sweden)ISG / 1997-201040 / 80931730.5 / 334.9 / 0.2100 / 8088 / NR53400 / 20 / NRMahr, A. et al. Southern Europe (SeineSaint-Denis County, France)ISG / 200379 / 109441227.6 / 437.1 / NR100 / 8090 / 20515910 / NR / 10Salvarani, C. et al. SouthernEurope (Reggio Emilia, Italy)ISG, 1988-200518 / 48696133 / 503.7 / 0.24100 / 78100 / NR565011 / 6 / NRAzizlerli, G. et al. Middle East (Istambul, Turkey)ISG / prevalence study101 / 23986NR / 48.542 / NR100 / 70.2Not globally reported / 69.327.7Not globally reportedNR / Not globally reported / NRDavatchi, F. et al. Middle East (Iran nationwide)Expert opinion / 1975-20187641 / NR25.6 / 44.280 / NR97.5 / 64.462.2 / 50.455.638.13.9 / 8.9 / 6.8Krause, I. et al. Middle East (Galilee, Israel)ISG / 15 years (not specific years have been reported)112 / 73700030.6 / 4715.2 / NRNR / 6841 / 44.4587011.6 / Not globally reported / NRNishiyama, M. et al. Asia (Japan nationwide)1987 JCBD / 19913316 / NR35.7 / 50.6NR / NR98.2 / 73.287.1 / 43.869.156.911 / 8.9 / 15.5JCBD: Japanese diagnostic Criteria of Behçet’s Disease; n: number of cases; NR: Not ReportedConclusion:BD’s prevalence in Northern Spain is higher than in most European populations. These differences likely reflect a combination of true geographic variation, methodological artifacts as well as the easy access to Public Health System and its efficiency. In contrast, clinical phenotypes are similar to other regions.References:[1]Lancet. 1990; 335:1078-80[2]J Eur Acad Dermatol Venereol. 2014; 28:338-47Disclosure of Interests:Lara Sanchez-Bilbao: None declared, Guillermo Suárez-Amorín: None declared, Carmen Álvarez-Reguera: None declared, Alba Herrero-Morant: None declared, David Martínez-López: None declared, José Luis Martín-Varillas: None declared, M. Cristina Mata Arnaiz: None declared, Rosalía Demetrio-Pablo: None declared, Miguel A González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Celgene and MSD., Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: AbbVie, MSD and Roche.

Background:Cystoid Macular Edema (CME) is the most important cause of blindness in non-infectious uveitis (NIU) (1). Corticosteroids and conventional and/or biological immunosuppressant may be required (1-6). High-dose intravenous methylprednisolone (IVMP) pulse therapy may induce a rapid improvement.Objectives:To evaluate the efficacy and safety of IVMP pulse therapy in CME of different immune mediated inflammatory diseases (IMID).Methods:Multicentre study of 66 patients with severe ocular inflammation who received IVMP. The underlying diseases were: Vogt Koyanagy Harada disease (VKHD)(n=24), Behçet’s disease (BD) (19) and idiopathic NIU (23). The main outcome variable was macular thickness and macular edema (Optical coherence tomography [OCT] >300 μm); that was assessed at 0 (basal), 2-5, 7, 15 and 30 days after IVMP.The results are expressed as mean ±SD for normally distributed variables, or as median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test.Results:We studied 43♀/ 23♂ patients. The main features are shown in TABLE 1. IVMP dose ranged from 250 to 1000 mg/day administered for 3-5 consecutive days, the dose was established according to the presence or not of other systemic manifestations apart from uveitis. All of them had active intraocular inflammation at the moment of the study.Table 1.Main features of 66 patients with cystoid macular edema.VKHD(n=24)Idiophatic(n=23)Behcet’s disease(n=19)Overall(n=66)Men/Women, n5/199/149/1066Mean age (years)42 ± 1147 ± 1533 ± 10-Unilateral/Bilateral, n (%)2 (8.3) /22 (91.7)10 (43.5) /13 (56.5)4 (21) /15 (79)16/50Inflammatory ocular patterns, n (%) Posterior uveitis6 (25)9 (39.1)3 (15.8)18 Panuveitis18 (75)14 (60.9)16 (84.2)48Laboratory data, n (%) ANA2 (8.34)2 (8.7)0 (0)4 HLA B270 (0)4 (17.4)0 (0)4 HLA B290 (0)1 (4.3)0 (0)1 HLA B510 (0)5 (21.7)8 (42)13A rapid and maintained statistically improvement was observed in OCT values in all underlying diseases (FIGURE 1). No major side effects were observed.Conclusion:High-dose IVMP pulse therapy is useful and safe in the prompt control of CME, regardless of the underlying IMID.References:[1]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019.[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576.[3]Santos-Gómez M, et al. Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359.[4]Atienza-Mateo B, et al. Rheumatology (Oxford) 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480.[5]Atienza-Mateo B, et al. Arthritis Rheumatol. 2019; 71(12):2081-2089. doi: 10.1002/art.41026.[6]Martín-Varillas JL, et al. Ophthalmology. 2018;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020.Figure 1.Improvement of OCT in 66 patients with cystoid macular edema.Disclosure of Interests:None declared

Objective To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis. Methods We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti–tumor necrosis factor (anti-TNF) agents. Results We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1–5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P

To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR).Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy.Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab. At TCZ onset they had macular edema (four eyes); visual acuity (VA) impairment (four eyes); vitritis (one eye); and diffuse angiographic signs of vasculitis (periphlebitis) (two eyes). Improvement of VA and OCT was observed following TCZ therapy in both patients. After a follow-up of 18 months (Patient 1) and 10 months (Patient 2), respectively, a corticosteroid sparing effect without any adverse effects was achieved in both cases.TCZ was effective in two patients with BSCR refractory to anti-TNF-α agents.

Background:Anti-TNFα agents are useful in uveitis(1-5).Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer.Objectives:To assess efficacy and safety of CZP in women with uveitis during pregnancy.Methods:Multicenter study of women with uveitis under CZP during pregnancy and their neonates.Results:14 women (23 eyes); mean age 34.3±5.5 yrs (TABLE 1). Pattern of uveitis: 10 anterior, 2 posterior, 1 intermediate, 1 panuveitis. Uveitis was bilateral in 9 and chronic in 7. CZP was started before conception in 10 patients and after in 4. All patients obtained or maintained ocular remission throughout pregnancy (FIGURE). Prednisone was reduced from a mean dose of 21.7±19.7 mg/day to 4.1±3.8 mg/day at 6 months (p=0.03), leading to complete discontinuation in 4. 15 healthy infants were born. Only 1 woman presented a mild infection. No infections or malformations were found in neonates after a follow-up of 6 months. 6 infants were breastfed and all received scheduled vaccinations without complications (TABLE 2).TABLE 1.AgeUnderlying diseaseImmunosuppressants before CZPCombined treatment134SpAMTX, AZA, ADAAZA237SpAMTX, AZA, IFX, ADA, GOLI339SpAAZA, ADAAZA446SpACyA, ETN, ADA, IFX, GOLI532SpASSZ, ADASSZ636SpAMTX, HCQ, ADA740SpAMTX, LFN, HCQ, IFX, ADA, GOLIHCQ831IdiopathicMTX, MMF, CyA, ADA933IdiopathicMTX, AZA, ADA, ETN1032RAMTXAZA1123Vogt-Koyanagi-HaradaAZA, ADAAZA1236Juvenil Idiopathic ArthritisADA1332Punctate inner choroidopathyADA1429BehcetCyA, IFX, ADAConclusion:CZP seems to be effective and safe in female patients with uveitis during pregnancy and neonates.References:[1]Llorenç V et al. Certolizumab Pegol, a New Anti-TNF-α in the Armamentarium against Ocular Inflammation. Ocul Immunol Inflamm. 2016;24(2):167-72. doi: 10.3109/09273948.2014.967779[2]Urruticoechea-Arana A et al. Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behçet’s disease associated uveitis: a systematic review. Rheumatol Int. 2019 Jan;39(1):47-58. doi: 10.1007/s00296-018-4193-z[3]Martín-Varillas JL et al. Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet’s Disease Ophthalmology. 2018 Sep;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020[4]Santos-Gómez M et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol. 2016. Sep-Oct;34(6 Suppl 102): S34-S40[5]Calvo-Río V et al. Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients.Semin Arthritis Rheum. 2016 Aug;46(1):95-101. doi: 10.1016/j.semarthrit.2016.03.002Disclosure of Interests:D. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Alfredo Adan: None declared, Lillian Chamorro-López: None declared, Olga Maiz: None declared, JR De Dios-Jiménez Aberásturi: None declared, Raul Veroz Gonzalez: None declared, Soledad Blanco: None declared, José M Santos: None declared, Francisco Navarro: None declared, Adela Gallego: None declared, Senen González-Suárez: None declared, Arantxa Conesa: None declared, Andrea García-Valle: None declared, Miguel Cordero-Coma: None declared, Nieves Pardiñas-Barón: None declared, Rosalía Demetrio-Pablo: None declared, Vanesa Calvo-Río Grant/research support from: MSD and Roche, Speakers bureau: AbbVie, Lilly, Celgene, Grünenthal, UCB Pharma, Victor Manuel Mora-Cuesta: None declared, Santos Castañeda: 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, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD

Background:The eye is a common and potential severe complication of sarcoidosis. Topical and systemic corticosteroids are the first-line treatment. Conventional and biological immunosuppressants (IS) are frequently needed(1-5).Objectives:To assess the frequency, clinical and treatment of ocular involvement of sarcoidosis.Methods:Study of a large cohort (n=383) of systemic sarcoidosis from a single university hospital. All consecutive patients diagnosed with sarcoidosis from January 1,1999 to January 1,2019 according the ATS/ERS/WASOG criteria(Eur Respir J 1999;14:735–737) were included.Results:41 (22 women/19 men) of 383 (10.7%) patients had ocular involvement, mean age 44.8±16 years. Uveitis (n=34; 82.9%) was the most common ocular manifestation, especially anterior uveitis (n=18; 52.9%). Ocular surface and eye orbit may also be affected(Table). In addition to topical and systemic corticosteroids, conventional (n=23; 56.1%) and biologic (n=14; 34.1%) IS drugs were required. Adalimumab and Infliximab were the most used biologic treatments(Table).Cystoid macular edema (CME) and Retinal Vasculitis was observed in both cases in 3 (7.3%) patients, 2 of them (66.7%) required biological treatment. Papilitis appeared in 7 (17.1%) cases, biological treatment was needed in 3 (42.9%) patients. The most frequent sequels were cataract (n=9, 21.9%), intraocular hypertension (n=5; 12.2%) and pupil alterations (n=4; 9.7%). The average of the best corrected visual acuity was 0.6±0.3 at diagnosis and 0.7±0.3 after one year follow up.Conclusion:Ocular involvement of sarcoidosis is a relative frequent and potential severe complication, especially if panuveitis is presented.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8.[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32:864-8.[3]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol. 2014; 32:275-84.[4]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94.[5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7.Table.Ocular manifestations of sarcoidosis and treatment with corticosteroids, conventional and biological IS.CONVENTIONAL ISBIOLOGICAL ISOCULAR INVOLVEMENTCasesTCSOCSMD of OCSIVMPCISMTXAZACFMMMFBTADAIFXTCZGLMETNSURFACE n(%)3(7.3)2(66.7)2(66.7)2(66.7)2(66.7)2(66.7)2(66.7)1(33.3)0(0)2(66.7)2(66.7)2(66.7)0(0)0(0)0(0)-CG/N, n(%)1(33.3)1(100)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)-PUK, n(%)2(66.7)1(50)2(100)602(100)2(100)2(100)2(100)1(50)0(0)2(100)2(100)2(100)0(0)0(0)0(0)UVEITIS n(%)34(82.9)25(73.5)28(82.3)10(29.4)19(55.6)18(52.9)7(20.6)1(2.9)1(2.9)12(35.3)11(32.3)4(11.8)3(8.8)2(5.9)1(2.9)-Anterior uveítis, n(%)18(52.9)11(61.1)13(72.2)301(5.5)5(27.8)5(27.8)1(5.5)0(0)0(0)0(0)0(0)0(0)0(0)0(0)0(0)-Posterior uveítis, n(%)4(11.7)2(50)3(75)601(25)3(75)2(50)2(50)0(0)0(0)2(50)1(25)0(0)0(0)1(25)0(0)-Panuveítis, n(%)12(35.3)12(100)12(100)608(66.7)11(91.7)11(91.7)4(33.3)1(8.3)1(8.3)10(83.3)10(83.3)4(33.3)3(25)1(8.3)1(8.3)EYE ORBIT n(%)4(9.7)2(50)3(75)2(50)2(50)2(50)2(50)0(0)0(0)2(50)1(25)1(25)1(25)0(0)0(0)-Proptosis, n(%)2(50)1(50)1(50)301(50)1(50)1(50)1(50)0(0)0(0)1(50)1(50)0(0)1(50)0(0)0(0)-Strabismus, n(%)2(50)1(50)2(100)601(50)1(50)1(50)1(50)0(0)0(0)1(33.3)0(0)1(33.3)0(0)0(0)0(0)TOTAL, n(%)41(100)29(70.7)33(80.5)50±15.514(34.1)23(56.1)22(53.7)11(26.9)2(4.9)1(2.4)14(34.1)14(34.1)7(17.5)3(7.3)2(4.9)1(2.4)TCS:topical corticosteroids;OCS:oral corticosteroids;MD:maximum dose;IVMP:intravenous methylprednisolone;CIS: conventional immunossupresors;BT:biologic therapy;CG/N:conjunctival granuloma/nodule;PUK:peripheral ulcerative keratitisDisclosure of Interests:Monica Calderón-Goercke: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Lara Sánchez-Bilbao: None declared, Rosalía Demetrio-Pablo: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Sarcoidosis is a multisystemic disease characterized by the formation of non-necrotizing granulomas. The most frequently affected organs are lungs, skin and eyes. Systemic corticosteroids are the most used drugs in the treatment of this disease. Conventional and biological immunosuppressants (IS) may also be used(1-3).Objectives:To evaluate the systemic treatment of sarcoidosis according to clinical domains.Methods:Study of all consecutive patients diagnosed with sarcoidosis between 1/1/1999 and 1/1/2019 in a tertiary university hospital. The diagnosis was established following the ATS/ERS/WASOG criteria(Eur Respir J. 1999;14(4):735-737):compatible clinical and radiological presentation, evidence of non-caseifying granulomas and exclusion of other granulomatous diseases.Results:We studied 377 patients (188 men/189 women), mean age at diagnosis of 46.0±14.8 years. After a mean follow-up of 13.0±9.3 years, 161 (42.7%) patients did not require treatment. The remaining 216 (57.3%) received oral glucocorticoids (206, 54.6%) with a maximum mean dose of 43.2±19.0 mg/day, conventional IS (60, 16.2%), biological therapy (28, 7.4%) and/or endovenous methylprednisolone (15, 4.0%). Biological therapy was indicated by pulmonary (9, 32.1%), ocular (9, 32.1%), neurological (3, 10.7%), muskuloeskeletal (3, 10.7%), cutaneous (2, 7.1%), nephrological involvement (1, 3.6%); and Heerfordt’s syndrome (1, 3.6%). Adalimumab and Infliximab were the biologics used more frequently (Table).TABLESystemic treatment of sarcoidosis according to clinical domains.Conclusion:Compared to other studies, the high percentage of patients who required systemic treatment is remarkable. It also highlights the frequency of the use of biological drugs in more severe organ involvement (ocular and neurological), which is consistent with the trend in recent years.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8.[2]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94.[3]Calvo-Río V, et al.. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7.Disclosure of Interests:Monica Calderón-Goercke: None declared, Raúl Fernández-Ramón: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Jorge Javier Gaitán-Valdizán: None declared, Rosalía Demetrio-Pablo: 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:Considerable epidemiological variations in prevalence of Behçet’s disease (BD) have been reported. These disparities may either reflect geographical differences, methodological artifacts, changes over time or random fluctuations. In Spain, published BD’s epidemiological studies are scarce.Objectives:To study epidemiological and clinical domains of BD in a well-defined population of Northern Spain, as well as, to compare results with other regions.Methods:We included all consecutive 111 patients, diagnosed of definitive or possible BD by expert rheumatologists between 1980 and 2019. Two Classification criteria were applied: a) International Study Group (ISG) for BD(Lancet. 1990; 335:1078-80), and b) International Criteria for BD (ICBD)(J Eur Acad Dermatol Venereol. 2014; 28:338-47). In addition, a literature review of Medline publications was carried out.Results:In our study, prevalence was higher than in most European populations regardless of the diagnostic criteria applied. Incidence was low (expert opinion: 0.021, ICBD: 0.016, ISG: 0.012). Mean age at onset (36.8±13.2) and gender distribution (55.9% females) were similar to other countries. Pathergy test was performed in 9% of patients giving low results (25.2%). Clinical domains’ frequency was in line with other regions except vascular and gastrointestinal involvement, which were lower. (TABLE)Conclusion:BD’s prevalence in Northern Spain is higher than in most European populations. These differences likely reflect a combination of true geographic variation, methodological artifacts as well as the easy access to Public Health System and its efficiency. In contrast, clinical phenotypes are similar to other regions.TABLEDiagnostic criteria and study periodn cases / population sizeMean age at onset and sex (%females)Prevalence (over 100000) / incidenceOral / genital ulcers (%)Skin lessions/ pathergy test (%)Ocular involvement (%)Joint involvement (%)Neurobehcet/ Vascular/ Gastrointestinal involvement (%)Herrero, A et al. Southern Europe (Cantabria, Spain)Expert opinion, ISG, ICBD / 1980-2019111 (expert opinion) / 86 (ICBD) / 65 (ISG) / 58107836.8±13.2/ 55.919.1 (expert opinion), 14.8 (ICBD), 11.2 (ISG) / 0.021 (expert opinion), 0.016 (ICBD), 0.012 (ISG)99 / 53.168.4 / 25. 235.168.518 / 10 / 4.5Calamia, K. T. et al. North America (Minnesota, USA)ISG / 1960-200513 / NR31 / 305.2 / 0.38100 / 6285 / NR624623 / 23 / NRAltenburg, A. et al. Northern Europe (Berlin, Germany)ISG and ABD classification tree / 1961-2005590 / 339134426 / 584.9 / 1 (estimated)98.5 / 63.762.5 / 33.758.15310.9 / 22.7 / 11.6Mohammad, A. et al. Northern Europe (Skane County, Sweden)ISG / 1997-201040 / 80931730.5 / 334.9 / 0.2100 / 8088 / NR53400 / 20 / NRMahr, A. et al. Southern Europe (Seine-Saint-Denis County, France)ISG / 200379 / 109441227.6 / 437.1 / NR100 / 8090 / 20515910 / NR / 10Salvarani, C. et al. Southern Europe (Reggio Emilia, Italy)ISG, 1988-200518 / 48696133 / 503.7 / 0.24100 / 78100 / NR565011 / 6 / NRAzizlerli, G. et al. Middle East (Istambul, Turkey)ISG / prevalence study101 / 23986NR / 48.542 / NR100 / 70.2Not globally reported / 69.327.7Not globally reportedNR / Not globally reported / NRDavatchi, F. et al. Middle East (Iran nationwide)Expert opinion / 1975-20187641 / NR25.6 / 44.280 / NR97.5 / 64.462.2 / 50.455.638.13.9 / 8.9 / 6.8Krause, I. et al. Middle East (Galilee, Israel)ISG / 15 years (not specific years have been reported)112 / 73700030.6 / 4715.2 / NRNR / 6841 / 44.4587011.6 / Not globally reported / NRNishiyama, M. et al. Asia (Japan nationwide)1987 JCBD / 19913316 / NR35.7 / 50.6NR / NR98.2 / 73.287.1 / 43.869.156.911 / 8.9 / 15.5Disclosure of Interests:Alba Herrero Morant: None declared, Guillermo Suárez Amorín: None declared, Lara Sanchez Bilbao: None declared, Carmen Álvarez Reguera: None declared, David Martínez-López: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Patricia Setien Preciados: None declared, M. Cristina Mata Arnaiz: None declared, Rosalía Demetrio-Pablo: None declared, Miguel Ángel Gordo Vega: None declared, Miguel Á. González-Gay Grant/research support from: AbbVie, MSD and Roche, Speakers bureau: AbbVie, MSD and Roche, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD

PURPOSE: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 ?m. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 ?m; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME. Funding/Support: The study was partially supported by RETICS Programs, 3 RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ 4 (ISCIII) (Spain).

Background Uveitis is the most common ocular manifestation in Behcet’s Disease (BD), which can cause irreversible blindness.1–2 Objectives To assess efficacy, safety and cost-effectiveness of adalimumab (ADA) therapy optimisation in a series of patients with uveitis due to BD. Methods Multicenter study of 74 ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Following remission, optimisation was performed by increasing the ADA dosing interval. Comparison between optimised and non-optimised group was performed. Results Ocular remission was achieved in 65 (86.6%) patients after a median ADA duration of 63–12 months. ADA was optimised in 23 cases. In the remaining 42 ADA was maintained at 40 mg/sc/2 weeks. No baseline differences were found at ADA onset between the optimised and non-optimised groups. Ocular outcomes were similar after a mean ±S.D. follow-up of 34.7±13.3 and 26±21.3 months in the both groups (table 1). Adverse effects were seen in non-optimised group (lymphoma, pneumonia, local reaction and bacteremia). Mean ADA treatment costs were lower in the optimised vs non-optimised group (6101.25 €/patient/year vs 12339.48). Conclusions ADA optimisation in BD uveitis refractory to conventional therapy is effective, safe and cost-effective. References [1] Calvo-Rio V, Blanco R, Beltran E, et al. Anti-TNF-alfa therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year- follow-up study of 124 patients. Rheumatol. 2014; 53(12):2223–31 [2] Santos-Gomez M, Calvo-Rio V, Blanco R, 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 (6Suppl 102):S34-S40 Disclosure of Interest None declared

Background Non ischaemic optic neuritis (NION) is a severe inflammation of the optic nerve that may lead to blindness. It can be primary or associated to immune-mediated inflammatory diseases (IMIDs). The treatment of the NION is based on systemic corticosteroids and conventional immunosuppressive drugs. Objectives To assess the efficacy of the biological treatment in refractory NION to conventional treatment. Methods Multicenter study of 8 patients diagnosed with NION refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were visual acuity (VA) and OCT of the optic nerve and the ganglionar cells. Comparisons were made between baseline and the 1st week, 1st and 6th month and 1st year. (STATISTICA, StatSoft Inc. Tulsa, Oklahoma, USA). Results We studied 8 patients (12 affected eyes) (4♀/4♂); mean age of 34.37±13.30 years. The underlying diseases were SLE (n=1), neuromyelitis optica (n=1), neuroretinitis (n=1), relapsing polychondritis (n=1), idiopathic (n=2) and Behcet’s disease (n=2). Before biological treatment and besides oral corticosteroids patients had received intravenous (IV) methylprednisolone boluses (n=6), cyclosporine A (CyA) (n=1), ciclophosphamide (n=2), micophenolate (n=2), hydroxycloroquine (n=1), methotrexate (MTX) (n=4) and azathioprine (AZA) (n=2). Biological treatment was based on rituximab (n=2) (2 IV. doses of 1 g/very 2 weeks and every 6 months), adalimumab (n=2) 40 mg/week, tocilizumab (n=2) 8 mg/kg/2–4 weeks and infliximab (n=2) 5 mg/kg at 0, 2 and 6 week and then every 8 weeks. The characteristics of the 8 patients are shown in the TABLE After biological treatment we observed an improvement in the ocular parameters: VA [0.60±0.33 to 0.76±0.41, p: 0.04], OCT of the optic nerve [130.63±60.54 to 102.60±8.17, p: 0.1] and OCT of the ganglionar cells [404.60±184.73 to 243±18.38, p: 0.17] at one year. After a mean follow-up of 27±14.47 months there were no severe adverse effects. Conclusions This study shows that treatment with biologic drugs, including ant-TNF drugs, in NION associated to IMIDs, refractory to conventional treatment, seems to be effective. These results must be confirmed in prospective and randomised trials. Disclosure of Interest None declared

Background Cystoid macular oedema (CME) represents the leading cause of blindness in uveitis of different immune-mediated inflammatory diseases (IMIDs). Objectives Our aim was to evaluate the efficacy of Tocilizumab (TCZ) in different IMIDs with refractory CME. Methods Multicentre study of 24 patients with CME due to uveitis of different IMIDs refractory to traditional treatment with systemic corticosteroids and at least one conventional immunosuppressive drug including in most cases biological therapy (n=21). CME was defined by (OCT >300 µm). We studied CME with TCZ in 4 different IMID; juvenile idiopathic arthritis (JiA), Behcet’s disease (BD), Birdshot retinochoroidopathy (BR) and idiopathic. The main outcome was the improvement of macular thickness. Other variables assessed were inflammation of the anterior chamber and vitreous and best corrected visual acuity (BCVA) Results We studied 16 ♀/8 ♂, mean age 35.2±19.3 years. The associated diseases were: JiA (n=9), BD,7 BR4 and idiopathic.4 The ocular patterns were: panuveitis,9 anterior uveitis,6 posterior uveitis5 and intermediate uveitis.4 Most patients had bilateral involvement.22 The biological therapy used before the administration of TCZ were infliximab,8 adalimumab,18 etanercept,2 golimumab,2 rituximab,2 abatacept,3 anakinra1 and daclizumab.1 TCZ administration schedule was 8 mg/kg/4 weeks iv.23 or every 2 weeks.1 TCZ was used in monotherapy12 or combined with conventional immunosuppressive drugs.12 OCT values improved considerably in 12 months: in JiA from 340.6±134.1 µm to 252.5±30 µm, in BD from 375.1±117 µm to 235±7.1 µm, in BR from 550.7±214.4 µm to 295.5±43.2 µm and in idiopathic from 515±219.6 µm to 208.3±46.7 µm (figure 1). Inflammation in anterior chamber and vitritis and BCVA also improved in the 4 subtypes. No minor side effects were observed, so no patient had to stop treatment. Conclusions TCZ seems a rapid effective treatment in severe and refractory uveitic CME, regardless of the underlying IMIDs. References [1] Calvo-Rio V, de la Hera D. et al. Tocilizumab in uveitis refractory to other biologic drugs: a study of 3 cases and a literature review. Clin Exp Rheumatol2014;32(Suppl 84):S54–S57. [2] Calvo-Rio V, Santos-Gomez M, et al. Anti-IL6-R Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to anti-TNF therapy. A multicenter study of 25 patients. Arthritis Rheumatol 2016;69:668–75. [3] Calvo-Rio V, Blanco R, Santos-Gomez M, et al. Efficacy of Anti-IL6-Receptor Tocilizumab in Refractory Cystoid Macular Edema of Birdshot Retinochoroidopathy Report of Two Cases and Literature Review. Ocul Immunol Inflamm2017Oct;25(5):604–609. Disclosure of Interest None declared

Objectives To assess the efficacy of Tocilizumab (TCZ) in refractory thyroid associated orbitopathy (TAO) due to Grave’s disease. Methods Multicenter study of 29 patients with TAO refractory to conventional immunosuppressive therapy. Results We studied 29 patients (58 eyes) (23 women/6 men); mean age at diagnosis 48.79±12.39 years. Besides oral corticosteroids and before the onset of TCZ, patients had been treated with pulses of intravenous methylprednisolone (n=24), methotrexate (n=2) and other drugs (methimazole in 4 cases, leflunomide in 1, selenium in 9). Urgent decompressive surgery had to be performed in 2 patients. According to the classification of severity of the EUGOGO group (European Group on Graves’ Orbitopathy) using the clinical activity score (CAS), before TCZ onset patients whose data were available had severe (n=14 eyes) or moderate (n=22 eyes) disease. Moreover, patients presented exophthalmos (n=30 eyes), strabismus (n=17 eyes), muscle fibrosis (n=15 eyes) and dysthyroid optic neuropathy (n=1). TCZ was used in monotherapy (n=27) or combined with methotrexate (n=2) at 8 mg/kg/iv/4 weeks (n=24) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement in all ocular parameters (TABLE). After a mean follow-up of 8.96±7.55 months using TCZ, all patients experienced ocular improvement, with TCZ withdrawal in 16 cases due to complete remission (n=5) or stability of ocular inflammation (n=11). Only 4 adverse effects were observed (neutropenia, external otitis, otitis media, costal osteitis). Conclusions TCZ appears to be useful in TAO treatment. Reference [1] Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid2008;18(3):333–346. Disclosure of Interest None declared

Background Cystoid macular oedema (CME) is the most serious complication of uveitis. This potentially severe complication may lead to irreversible visual loss.1–2 Objectives To compare efficacy and safety of Tocilizumab (TCZ) vs. Anti-TNF-α drugs in patients with refractory CME to conventional immunosuppressant (IS). Methods Multicenter study of patients with refractory CME to treatment with glucocorticoids and at least 1 conventional IS. The main objective was the improvement of macular thickness. Secondary objectives were the enhancement in best corrected visual acuity (BCVA) and the degree of ocular inflammatory activity. Results 59 patients/112 affected eyes. Causes of uveitis were: Behcet’s disease (n=41), Birdshot’s retinochoroidopathy (n=4), Juvenile Idiopathic Arthritis (n=9), Sarcoidosis (n=1) and idiopathic (n=4). No significant differences were observed at baseline in both groups (TCZ vs Anti-TNF-α) in sex (♂/♀; 8/17 vs. 15/19), mean age (35.6±18.9 vs 40.0±9.1), BCVA (0.40±0.31 vs. 0.48±0.31), Tyndall (1 [0–1] vs. 1 [0–2]), vitritis (1 [0–2] vs. 1 [0–3]) and macular thickness (431.8±165.9 vs. 397.1±138.1) (table 1). 25 patients were treated with TCZ as follows: 8 mg/kg/4 weeks (n=24) and 162 mg sc/2 weeks (n=1). Anti-TNF-α therapy was used in the remaining 34 as follows: IFX (n=12) (5 mg/kg 0, 2 y 6 weeks and every 4–8 weeks) and ADA (n=22) (40 mg/sc/2 weeks). We observed a rapid and sustained improvement in macular thickness after 1 year follow-up in both groups, without objectifying significant differences between them. In the same way, secondary ocular parameters also improved (table 1). Conclusions TCZ and Anti-TNF-α are effective in the treatment of CME refractory to conventional therapy. References [1] Calvo-Rio V, Blanco R, Beltran E, et al. Anti-TNF-alfa therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year-follow-up study of 124 patients. Rheumatol. 2014;53(12):2223–31. [2] Calvo-Rio V, Blanco R, Santos-Gomez M, et al. Efficacy of anti-il6-receptor tocilizumab in refractory cystoid macular edema of Birdshot retinochoroidopathy report of two cases and literature review. Ocul Immunol Inflamm. 2017;25(5):604–609. Disclosure of Interest None declared

Objectives To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as first biologic drug in refractory uveitis with cystoid macular oedema (CME) associated to BD. Methods Multicenter study of 40 patients with BD-associated uveitis with CME refractory or intolerant to standard treatment (corticosteroids and at least one conventional immunosuppressive agent). CME was considered if macular thickness was greater than 300 µm. Comparative outcome measures were macular thickness, improvement of visual acuity (VA), activity of anterior chamber inflammation and vitritis. Results were expressed as mean ±SD for variables with a normal distribution, or as median [25th-75th interquartile range- IQR] when not normally distributed. The comparison of continuous variables among time-periods was performed with the Wilcoxon signed rank test. Results We selected patients with CME from a cohort of 177 patients with refractory BD-related uveitis (n=40). IFX was used in 15 cases and ADA in 25. No significant differences at baseline were observed between IFX vs ADA groups in sex (♂/♀ 8/7 vs 13/12, p=0.93), mean age (38±9 vs 41±10 years, p=0.53), HLA-B51 + (10 vs 19, p=0.87), uveitis pattern (panuveitis 67% vs 80%, posterior uveitis 33% vs 20%, p=0.34), previous conventional treatment (intravenous pulses of methylprednisolone 60% vs 52%, p=0.62, oral corticosteroids 93% vs 72%, p=0.1, methotrexate 53% vs 52%, p=0.93, cyclosporin A 73% vs 88%, p=0.23, azathioprine 53% vs 56%, p=0.86, other drugs 47% vs 68%, p=0.18), and combined treatment (67% vs 64%, p=0.86). After 1 year of therapy, ocular remission was achieved in 60% of cases with IFX and in 76% of cases with ADA (p=0.28). Regarding CME, 65% of patients with IFX reached a macular thickness Conclusions IFX and ADA show a similar efficacy in the treatment of CME in BD-related refractory uveitis. Reference [1] Calvo-Rio V, Blanco R, Beltran E, Sanchez-Burson J, Mesquida M, Adan A, et al. Anti-TNF- therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year follow-up study of 124 patients. Rheumatology (Oxford)2014;53(12):2223–31. Disclosure of Interest None declared

Background This study shows that treatment with biologic drugs, including ant-TNF drugs, in NION associated to IMIDs, refractory to conventional treatment, seems to be effective. These results must be confirmed in prospective and randomised trials. Objectives Our aim was to compare anti-TNFα vs Rituximab (RTX) in refractory PUK. Methods Multicenter study of 24 patients with PUK. All of them presented inadequate response to corticosteroids and at least 1 systemic traditional immunosuppressive drug. Anti-TNFα were used in 17 patients: Adalimumab (n=9) 40 mg/sc every 1–2 weeks, infliximab (IFX) (n=7) 3–5 mg/kg iv/4–6 weeks, etanercept (n=1) 50 mg/week. RTX was used in 7 patients 1–2 g i.v. every 6 or 12 months. The main outcomes were Best Corrected Visual Acuity (BCVA), signs of inflammation (scleritis and episcleritis), progression to corneal thinning, central keratolysis and ocular perforation. Results We studied 24 patients/32 affected eyes. The underlying diseases in the anti-TNFα group were Rheumatoid Arthritis (RA) (n=14), Psoriatic Arthritis (n=2) and Behcet Disease (n=1); and in the RTX group: RA (n=5), granulomatous polyangiitis (n=1) and microscopic polyangiitis (n=1). At baseline there were no significant differences between both groups in general features or in ocular involvement (table 1). Before biologic therapy they had received the following systemic drugs (anti-TNFα vs RTX) i.v. methylprednisolone (2 vs 4), doxycycline (7 vs 1), ascorbic acid (2 vs 0), MTX (11 vs 4), AZA (1 vs 2) and others (7 vs 3). In addition,10 patients, in both groups, had required surgery: amniotic membrane (n=5), penetrating keratoplasty (n=2), conjunctival resection (n=2), tissue adhesives (n=2), conjunctival flap (n=1) and lamellar keratoplasty (n=1). Once the treatment was initiated the ocular outcome was similar (table 1). After a mean follow-up of 22.53±22.60 (anti-TNFα) and 22.28±8.28 months with RTX the following severe side effects were observed: supraventricular tachycardia (n=1) with RTX and pulmonary tuberculosis (n=1) with IFX. Conclusions In this study, anti-TNFα therapy and RTX were equally effective for the treatment of peripheral ulcerative keratitis associated to rheumatic diseases refractory to conventional treatment. Disclosure of Interest None declared

Objectives To assess the efficacy of Tocilizumab (TCZ) in refractory uveitis associated to extraocular manifestations due to Behcet’s disease (BD). Methods Multicenter study of patients with BD refractory to standard systemic treatment (conventional immunosuppressive drugs and/or anti-TNF-α agents). Results We studied 11 patients (7 men/4 women) (20 affected eyes); mean age 38.4±20.4 years. Uveitis was bilateral in 9 patients. The pattern of ocular involvement was: panuveitis (n=8; with retinal vasculitis in 4), anterior uveitis (n=2) and posterior uveitis (n=1). Cystoid macular oedema (CME) was present in 7 patients. The clinical course was recurrent (n=7) or chronic (n=4). Apart from the visual complications, at TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n=7), arthritis (n=4), folliculitis/pseudofolliculitis (n=4), erythema nodosum (n=2), livedo reticularis (n=1), intestinal affection (n=1), and neurological involvement (n=2). Before TCZ, they had received systemic corticosteroids, conventional immunosuppressive drugs and biologic agents, adalimumab (n=8), infliximab (n=4), golimumab (n=3), canakinumab (n=1), or etanercept (n=1). TCZ was used in monotherapy or combined with conventional immunosuppressive drugs at 8 mg/kg/iv/4 weeks (n=10) or 162 mg/sc/week (n=1). TCZ yielded rapid and maintained improvement in all ocular parameters (TABLE). After a mean follow-up of 9.5±8.05 months using TCZ, all patients experienced ocular improvement, with complete remission in 8 of them. However, TCZ was only effective in 3 of the patients with extraocular manifestations. This biologic agent had to be withdrawn in 2 cases, 1 due to a severe infusion reaction and 1 due to arthritis impairment. Abbreviations: CME, cystoid macular oedema; MRI, magnetic resonance imaging; TCZ, tocilizumab. Conclusions TCZ appears to be useful in highly refractory BD-related uveitis. However, there are controversial results regarding its efficacy in the treatment of extraocular manifestations of BD. References [1] Santos-Gomez M, Calvo-Rio V, Blanco R, Beltran E, Mesquida M, Adan A. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicenter open label study. Clin Exp Rheumatol2016;34(6Suppl 102):S34–S40. [2] Calvo-Rio V, de la Hera D, Beltran-Catalan E, Blanco R, Hernandez M., Martinez-Costa L. Tocilizumab in uveitis refractory to other biologic drugs: a study of 3 cases and a literature review. Clin Exp Rheumatol2014;32(Suppl 84):S54–S57. [3] Calvo-Rio V, Santos-Gomez M, Calvo I, et al. Anti-IL6-R Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to anti-TNF therapy. A multicenter study of 25 patients. Arthritis Rheumatol2016;69:668–75. Disclosure of Interest None declared

Purpose: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behcet disease (BD) who achieved remission after the use of this biologic agent. Design: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Subjects: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. Methods: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Main Outcome Measures: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. Results: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean +/- standard deviation follow-up of 34.7+/-13.3 and 26+/-21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). Conclusion: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and costeffective. (C) 2018 by the American Academy of Ophthalmology

Background Uveitis is a severe manifestation of Juvenil Idiopathic Arthritis (JIA). Anti-TNFa are recommended in refractory cases, mainly infliximab (IFX) or adalimumab (ADA) (Levy-Clarke et al. Ophthalmology 2014; 121: 785–796). However, sometimes they are ineffective, contraindicated or not tolerated. The next therapeutic step is not defined. Objectives To compare the efficacy of Golimumab (GLM) and Tocilizumab (TCZ) in related AIJ uveitis refractory to conventional immunosuppressive drugs and anti-TNFα. Methods Multicenter study of 33 patients with uveitis associated-JIA. They were refractory to conventional treatment with high dose of corticosteroids and at least a) one conventional immunosuppressive drug and b) one anti-TNFa. For this reason it was decided to iniciate TCZ or GLM. TCZ was used in 25 patients: 8 mg/kg/4 w iv (n=21), 8 mg/kg/2 w (n=2); 8 mg/kg/8 w (n=1) and 2.9 mg/kg sc/w (n=1). GLM was used in 8 patients (50 mg/sc/month). We assessed visual acuity (VA), degree of intraocular inflammation, vitreous inflammation and macular thickening (with OCT). Quantitative variables were expressed with mean±SD or median [IQR], according to its distribution. They were compared with the Student t or the Mann-Whitney U test, respectively. Dichotomous variables were expressed as percentages and compared by the chi-square test. Results We studied 33 patients/61 affected eyes. There were no significant differences between TCZ and GLM at baseline in sex (♂/♀;4/21 vs 3/5; p=0.19), mean age (18.5±8.3 vs 19.9±8.7; p=0.55), positive ANA (95% vs 100%; p=0.7), uveitis duration before TCZ or GLM onset (116.4±93.6 vs 142.3±74.7 p=0.46), number of previous biological treatments (1.9±1.1 vs 2±1.4; p=0.84), VA (0.57±0.35 vs 0.5±0.37; p=0.42), combined immunosuppressive therapy (88% vs 75%; p=0.37), presence of cells in the anterior chamber (median, 1 [0–1] vs 1 [0.25–1.5]; p=0.6), vitritis (0 [0–0] vs 0 [0–1]; p=0.7), macular thickening (358.7±92.2 vs 313.6±77.1; p=0.32). There were no significant difference in the efficacy between TCZ and GLM (TABLE). After a mean follow-up of 20.48±11.7 months with TCZ and 24.25±17 months with GLM the following side effects were observed: TCZ: viral conjunctivitis plus bullous impetigo (n=1), severe thrombocytopenia and pneumonia. This last patient showed hemolytic anemia, thrombocytopenia and splenomegaly, for this reason treatment with TCZ was discontinued. With GLM cutaneous reaction was observed in 2 patients. Conclusions TCZ and GLM seem to be equally effective and safe for refractory uveitis associated-JIA. The superiority of one or the other should be established with prospective randomized studies “Head to Head” Disclosure of Interest None declared

Objectives To assess the efficacy of tocilizumab (TCZ) at short and long term follow-up for severe juvenile idiopathic arthritis-associated uveitis. Methods Multicentre study of 25 patients who had inadequate response to traditional treatment with corticosteroids and at least one conventional immunosuppressive drug including biological therapy. The outcome variables were the degree of inflammation, visual acuity and macular thickness. The results are expressed as mean±SD for normally distributed variables, or median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test. Results We studied 25 patients (21 women/4 men); mean age 18.6±8.3. Uveitis was bilateral in 22. JIA subsets were oligoarthritis (n=17), polyarthritis (5), psoriatic (2) and enthesitis-related arthritis (1). Ocular sequelae at TCZ onset were cataracts (13), glaucoma (7), synechiae (10), band keratopathy (12), maculopathy (9), and amblyopia (5). Pattern of uveitis was: anterior (17), panuveitis (4), intermediate (2) and posterior (2). Before TCZ, they had received corticosteroids, conventional immunosuppressive drugs and biologics, including adalimumab (24), etanercept (8), infliximab (7), abatacept (6), rituximab (2), anakinra (1), and golimumab (1). TCZ dosage regimen was 8 mg/kg IV/4 weeks (21), every 2 weeks (2), every 8 weeks (1), or 2.9 mg/kg sc every week (1). All outcome variables showed a rapid and maintained improvement (Table 1) after a follow up of one year (n=21), 2 years (n=11), and 3 years (n=5). A reduction in the daily median dose of prednisone from 10 mg [0–15 mg] to 0 [0–0 mg] in 3 years, (p Conclusions TCZ is useful at short and long term follow-up for severe Juvenile Idiopathic Arthritis-associated uveitis. It is possible to optimize the TCZ dose. Disclosure of Interest None declared

Objectives To assess the long term efficacy and optimization of Infliximab (IFX) in refractory Uveitis of Behcet Disease (BD) Methods Multicentre study of Uveitis associated-BD refractory to conventional immunosupressive drug. Ocular inflammation was evaluated with “SUN criteria” (Am J Ophthalmol 2005;140:509–516) and the macular thickening with OCT. Results are expressed as mean±SD or median [IQR] (comparison, Wilcoxon test) Results We studied 100 patients/180 affected eyes (54M/46W), mean age 40.7±10.1. The ocular pattern was panuveitis (n=62), posterior (27) and anterior uveitis (11). Before IFX they received iv MP (28), cyclosporine (75), azathioprine (56), metotrexate (43) and others (33). IFX dose ranged between 3–5mg/kg/4 or 8 weeks. In patients in remission IFX was optimized (n=28) or stopped (n=20). Conclusions IFX is an effective long term-treatment in refractory Uveitis of BD. Optimization and even discontinuation of IFX after remission is possible. Disclosure of Interest None declared

Objectives To evaluate the efficacy of adalimumab (ADA) in short and long term follow-up in refractory uveitis of Behcet9s disease (BD) Methods Multicenter study. Ocular inflammation was evaluated according to “SUN working Group” (Am J Ophthalmol 2005;140:509–516), and the macular thickening with OCT. A comparison was carried out between baseline, and follow-up visits. Results are expressed as mean±SD or median [IQR]. Continuous variables were compared with Wilcoxon test. Results We studied 74 patients/132 affected eyes (39M/35W); mean age 38.7±11.3. The ocular pattern was panuveitis (n=45), posterior uveitis (n=14), anterior uveitis (n=14) and intermediate uveitis (n=1). Before ADA, systemic treatment with corticosteroids, iv metilprednisolone (n=23), Cyclosporin A (58), azathioprine (33), metotrexate (31) and other drugs (28) was used. The dose of ADA was 40 mg/2 weeks/ sc in monotherapy (n=22) or combined (n=52). Most patients showed a rapid and progressive improvement (TABLE). The 24 patients (37 affected eyes) with CME showed a significant improvement. ADA was optimized in 23 (31.1%) that were in remission for 15.3±9 months. Interval of administration was increased to 3 (n=6), 4 (13), 5 (1), 6 (1) and 8 weeks. After a mean follow-up of 13.0±9.7 months after optimization, 21 patients were stable and 2 had a severe flare. In 4 patients ADA was stopped after 35.2±9.3 months in remission. The main adverse effects observed were lymphoma (n=1), pneumonia (1), and 2° bacteriemia by E. Coli (1) Conclusions ADA was effective in short and long-term follow-up in refractory uveitis associated to BD. Optimization or even suspension of ADA is possible. Disclosure of Interest None declared

Background The prevalence of thrombosis in antiphospholipid syndrome (APS) and the factors vary depending on the population studied. Although aPL have a strong relationship with thrombosis and pregnancy morbidity, the value of each type of aPL as a marker to develop APS it is not fully clarified. Objectives To analyze the incidence of thrombosis in patients with positive aPL that do not meet clinical criteria for disease. To identify potential risk factors for thrombosis. To analyze the possible protective role of primary thromboprophylaxis. Methods Retrospective study of patients with positive aPL on at least 2 times, separated by a minimum of 12 weeks in medium or high titers without fulfilling clinical criteria for APS. The patients were selected from the database of the Department of Immunology of a tertiary hospital (1999- 2004). The presence of vascular event was confirmed through imaging tests. Cases of ischemic optic neuropathy (ION) were diagnosed by clinical and electrophysiological testing. Results After a mean follow-up of 146±60.3 months, of the 138 patients included in the study, 13 (9.4%) developed thrombosis. The mean time to thrombotic episode was 81.4±41.7 months. Several classic cardiovascular risk factors (CVRF) such as tobacco (61.5% in thrombosis group vs 23.2% in the group without thrombosis;p=0.003), hypertension (53.8% vs 15.3%;p=0.001) and dyslipidemia (DLP) (38.5% vs 5.6%;p=0.001) were more frequent in patients with thrombosis. These 3 classic CVRF were independent risk factors for thrombosis in the univariate analysis, with an OR of 6.5 (95%CI 2.0–21.3) for hypertension, 5.3 (95%CI 1.6–17.5) for tobacco and 10.5 (95%CI 2.7–40.8) for DLP. Regarding the different antibodies, only the lupus anticoagulant (LA) (p=0.062) and anticardiolipin antibodies (aCL) IgM (p=0.14) tended to be more frequent in patients with thrombosis. Positivity to the 3 types of antibodies (AL, aCL, AB2GPI) was associated with increased risk of thrombosis (OR 7 [95%CI 1.9–28.5]; p=0.004). Multivariate analysis showed as independent risk factors for thrombosis: smoking (OR 8.3 [95%CI 1.3–52.5]; p=0.024), hypertension (OR 15.9 [95%CI 1.8–138.7]; p=0.012), DLP (OR 16.9 [95%CI 1.4–108.3]; p=0.027) and IgM aCL (OR 18.7 [95%CI 12–277.7]; p=0.033). Of the 13 thrombotic events, 10 were arterial: 4 acute myocardial infarctions, 2 thrombosis of central retinal artery, 2 OIN 1 transient ischemic attack and 1 stroke. Three thrombosis occurred in venous territory as deep venous thrombosis of lower extremities, with secondary pulmonary thromboembolism in 2 patients. Regarding treatment, 102 patients received prophylaxis with ASA 100 mg, showing a tendency towards protection (OR 0.774 [95%CI 0.2–2.7]; p=0.686). Conclusions The incidence of thrombosis in patients with positive aPL that do not meet clinical criteria for the disease is about 10%. The tobacco, DLP, hypertension and IgM aCL are independent risk factors. Autoantibodies load increases the risk of thrombosis. The protective role of aspirin in this population seems limited and may raise primary thromboprophylaxis with oral anticoagulation in patients considered as high risk. Disclosure of Interest None declared

Background Antiphospholipid Syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis and/or pregnancy morbidity together with the presence of positive antiphospholipid antibodies (aPL) (anticardiolipin antibodies (aCL), anti -beta2 glycoprotein I (AB2GPI) and/or lupus anticoagulant (LA). There is a clear relationship between aPL and some events not included in the clinical criteria such us the hematologic manifestations. Among these, thrombocytopenia has been described in 20–50% of patients with APS. Although thrombocytopenia in APS is usually not serious, its impact on the clinical curse of the diseasesis unknown. Objectives a) To study the probability of developing clinical APS in patients with positive aPL and thrombocytopenia b) To identify potential risk factors for the development of APS. c) To study the association of thrombocytopenia with aPL autoantibodies. Methods Retrospective study of patients with positive aPL on at least 2 times, separated by a minimum of 12 weeks in medium or high titers without fulfilling clinical criteria for APS. The patients were selected from the database of the Department of Immunology of a tertiary hospital (1999–2004). Thrombocytopenia was defined as a platelet count ≤100000 platelets/L. We excluded patients with other causes of thrombocytopenia. Results 17 of 138 (12%) patients in the study had thrombocytopenia (mean platelet count 60,000/mm 3 ). Ten patients received oral glucocorticoids. Only 2 patients with 3 were treated with intravenous gammaglobulins. Smoking was more common in patients with thrombocytopenia (47.1% vs 24%; p=0.044). The risk for thrombocytopenia was almost 3 times higher in smokers (OR 2.8; 95%CI 1.0–8.0; p=0.044). We found no statistically significant relationship with the distribution of the different antibodies, except for AL (OR 13.5, 95%CI 3.8–47.6; p After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis (4 arterial: 1 anterior ischemic optic neuropathy, 1 transient ischemic attack, 1 stroke and 1 acute myocardial infarction, and 1 deep venous thrombosis of the lower limbs with secondary pulmonary embolism), fulfilling clinical criteria for APS. The mean time from the confirmation of the presence of aPL to the diagnosis of APS was 73±61.5 months. Patients with thrombocytopenia had higher number of thrombosis compared with patients with normal platelet count (29.4% vs 6.6%, OR 5.9; 95%CI 1.7–20.9; p=0.003). Conclusions a) In our series, the incidence of thrombocytopenia in patients with positive antiphospholipid antibodies that do not meet clinical criteria for APS is 12%. APL-positive patients who develop thrombocytopenia have a potential risk of developing APS in the future. b) Tobacco use could be a risk factor for the development of thrombocytopenia in this population. c) Autoantibodies load is a risk factor for the development of thrombocytopenia. Disclosure of Interest None declared