Search

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.

To describe the clinical and therapeutic management of rheumatoid arthritis (RA) patients with biological disease-modifying antirheumatic drugs (bDMARDs), alone or in combination with conventional synthetic DMARDs (csDMARDs), as well as analysing changes over time in bDMARD use. An observational, retrospective, multicentre study was conducted in the rheumatology departments of 10 public Spanish hospitals. Patients with RA treated with bDMARDs at baseline who had medical records available in the data collection period 2013-2016 were included. All visits to rheumatology departments recording any type of bDMARD modification (dose, etc.) were collected. Clinical characteristics, concomitant treatment, resource use, work productivity and quality of life (QoL) were recorded. 128 patients were included: 81 received first-line bDMARD treatment, 28 second-line bDMARD treatment and 19 received third or later lines. Mean study follow-up was 4.1 years. Assessment of DAS28 was available in 54.6% of visits. At baseline, 48.7% of patients had moderate-high disease activity. At final observation, 69.5% of patients continued with the first bDMARD. Tumour necrosis factor blockers were administered to 85.2% of patients in first line, 45.7% in second line and 18.1% in third or later lines. At final observation, 80.2% of patients still felt pain/discomfort. As expected, those with higher disease activity had higher loss of work productivity and lower QoL, as assessed by DAS28, than patients with lower disease activity. Drugs represented 82.6% of the total cost. In this Spanish cohort of 128 patients, most patients remained on the first prescribed bDMARD, despite remaining signs and symptoms.

The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS). This process is an inflammatory picture, involving an NLRP3 INFLAMOSOME-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. ANAKINRA is a potent biological drug, capable of blocking this IL 1 beta. We propose its use in controlling ARDS secondary to COVID-19 infection.

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: Tofacitinib (TOFA) is the first inhibitor of JAK kinases with approval for the treatment of psoriatic arthritis (PsA) in Europe (July 2018)1. ToFA has shown efficacy in refractory patients to anti-TNF2. Objectives: A) to assess efficacy and safety of TOFA in the first cases in Spain in clinical practice. B) to compare the profile of clinical practice patients with clinical trial. Methods: Study of 41 patients of clinical practice with PsA treated with TOFA in Spain. The diagnosis of PsA was made using CASPAR criteria. Patients who received at least one dose of TOFA were included. Results are expressed as percentage, mean±SD or median [IRQ]. Results: 41 patients (23♀/18♂), mean age of 50.2±10.7 years (table 1). Pattern joint involvement was as follows: peripheral (n=25), axial (1) and mixed (15). During the PsA evolution, in addition to arthritis, patients also presented enthesitis (60.9%), nail involvement (39%) and dactylitis (31.7%). Prior TOFA, most patients had received oral prednisone or equivalent (max. 17.9±13.6 mg/d), synthetic immunosuppressants (mean 1.9±0.7) and biological therapy (TB) (3.4±1.9). TB were as follows: etanercept (29), adalimumab (29), infliximab (16), golimumab (13), certolizumab (14), secukinumab (30), ustekinumab (22). Apremilast was used in 10. After a mean follow-up of 12.6±9.1 years after the PsA diagnosis, TOFA was started (5 mg/12 h). 60.9% associated prednisone (9.4±6.1 mg/d). In 17 (41.5%) TOFA was started in combined therapy: methotrexate (9) and leflunomide (8); in the remaining 24, monotherapy was prescribed. In addition to active arthritis patients presented skin involvement (53.6%), enthesitis (26.8%), nail involvement (29.2%) and dactylitis (17.1%). Patients of clinical practice compared with clinical trial have a longer duration of PsA, functional disability (HAQ) and received a higher proportion of corticosteroids and TB (anti-TNF and non-anti-TNF) (table 1). After a median follow-up of 4 [3-10.5] months, patients showed prompt improvement in the main variables, both in activity indexes (PASI, DAS28, DAPSA) and laboratory test (table 2). Minor side effects were reported in 10 patients (gastrointestinal symptoms), and TOFA was discontinued in 1 due to persistent symptoms. Conclusion: In this preliminary study, first patients of clinical practice in Spain with TOFA in PsA had a longer evolution and received a greater number of TB than those of clinical trial. As in the TOFA clinical trial, it seems effective, rapid and relatively safe in daily clinical practice for refractory PsA. References [1] https://www.ema.europa.eu/documents/overview/xeljanz-epar-medicine-overview_es.pdf [2] Gladman D. N Engl J Med2017; 377: 1525-36. Disclosure of interests: Jose Luis Martin-Varillas: None declared, Eva Galindez: None declared, Esteban Rubio Romero: None declared, agusti Sellas-Fernandez: None declared, Roberto Daniel Gonzalez Benitez: None declared, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, abbVie, and Janssen, Jose Campos Esteban: None declared, Olga Rusinovich: None declared, Vanesa Calvo-Rio: None declared, Francisco Ortiz-Sanjuan: None declared, Clara Ventin-Rodriguez: None declared, Luis Fernandez-Dominguez Speakers bureau: Celgene, Novartis, Janssen, antia Crespo Golmar: None declared, Ximena Elizabeth Larco Rojas: None declared, Manuel Moreno : None declared, alejandro Escudero Contreras: None declared, Emma Beltran: None declared, Rafael Melero: None declared, Maria jose Moreno: None declared, Enrique Raya: None declared, Beatriz arca: None declared, Maria-Luisa Peral: None declared, Olga Maiz: None declared, Raul Veroz Gonzalez: None declared, alfonso Corrales: None declared, Natalia Palmou-Fontana: None declared, Belen atienza-Mateo: None declared, J. Loricera: 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 Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology, and approximately 60% or 70% of the patients can develop a chronic poliphasic form of the disease or a chronic polyarthritis. Due to the rarity of this disease, the treatment of AOSD is not based on a controlled study, but in the experience based on real cases. Objectives Describe the different treatments employed in a patient cohort diagnosed with adult-onset Still’s disease (AOSD). Methods Descriptive, restrospective study of patients treated in our Hospital (2008-2018), diagnosed with AOSD according to the classification criteria of Yamaguchi. The data were achieved by the review of the clinical records. Results Twenty-four patients (15 women), average age of 41±13 years, were included. Two women, with presentation on the symptoms at 8 and 3 years old, first diagnosed with systemic juvenile idiopathic arthritis (S-JIA), and then with AOSD. The initial treatment was based in non-steroidal anti-inflammatory drugs (96%) and glucocorticoids (0,5-1 mg/kg/day) (96%) for symptom control, with the necessity to add oral or subcutaneous methotrexate at a dose of 15 mg per week in 13 patients (54%). Only two patients used acetyl salicylic acid as initial treatment, with no improvement. Five patients used also biological treatments with a standard doses, with the neccesity of various drugs to achieve their clinical remission. Nowadays, all patients have their clinical remission. Patient 1: Infliximab, rituximab, tocilizumab and baricitinib. Patient 2: Etanercept and rituximab. Patient 3: Etanercept, adalimumab and infliximab. Patient 4: Etanercept, infliximab and tofacitinib. Patient 5: Infliximab, tocilizumab, baricitinib and sarilumab (great responde to a anti-IL6, tocilizumab were removed because of a local reaction in the injection’s spot, althought it had a good response too). Two patients with clinical remission with JAK-kinase inhibitors (baricitinib and tofacitinib, respectively), one patients with anti-TNF (infliximab) and another one with anti-CD20 (rituximab). Conclusion In general, our results match with what it is published in the literature. For the treatment of AOSD has been used high doses of ASA (4g/day) or NSAID. However, the required doses (with their respective adverse effects), its limited responses and the frequent relapses after its suppression make difficult to maintain it. Nowadays, the systemic glucocorticoids are our first choice (0,5 to 1 mg/kg/day). A high average of our patients have a positive response with it, but in a 54% of the cases were neccesary to add methotrexate or others DMARDs because of a partial response with steroids. In the physiopathology of the AOSD there is an increase of pro-inflammatory cytokines, as the tumor necrosis factor, IL-1 e IL-6. The use of therapies that inhibit these molecules (anti-TNF, anakinra or canakinumab as anti-IL1 or tocilizumab or sarilumab as anti IL-6) is being a progress. The inhibitors of IL-1 can be more efficient for systemic manifestations, while the inhibitors of IL-6 are for articular and systemic affectation. The TNF inhibitors should being used for the articular affectation only. In our patient cohort there is no patient with anti-IL1, a patient in clinical remission with anti-TNF and another one with anti-IL-6. Prospective studies with a higher number of patients is neccesary to define better the AOSD treatment. Disclosure of Interests None declared

Background Sarcoidosis (S) is a systemic granulomatous disease of unknown etiology. The most frequent affectation is pulmonary, ocular and cutaneous, although sarcoidosis can damage other organs, such as the musculoskeletal system. Objectives To describe the clinical characteristics and the radiological pattern, in a cohort with predominant pulmonary S, as well as to establish the relationship between the angiotensin converting enzyme (ACE) levels and the S course (chronification or remission). Methods This is a retrospective descriptive study of patients treated in our hospital, since 2008 to 2018, with diagnosis of S. The data was obtained through the review of medical records. The delay in the diagnosis of S was defined as the difference in months between the initial diagnostic suspicion and the final diagnosis of S. We use Chi-square tests to study the association between ACE levels and the course of the disease. Results Fifty-five patients (31 women) were included, with a mean age of 52 ± 12 years. The first diagnosis was: 85% S, 10% lymphoma and 4% tuberculosis. The median of months for the definitive diagnosis of S was 5.5 months. Extrapulmonary clinical manifestations in table 1. The ACE is increased in 38 patients (70%). Simple x-ray and high resolution tomography of chest were done in all patients. Pulmonary stage 2 was the most frequent (51%), followed by stage 3 (16%), stage 0 (14%) and stage 4 (9%). In 90% of the patients, histological confirmation was obtained by transbronchial (47%), cutaneous (11%) or lymph node biopsy (29%). 94% of the patients have been treated with oral glucocorticoids, 52% associate immunosuppressive therapy (Methotrexate 27% and Azathioprine 14%) or biological treatment (1 patient with Adalimumab and another with Infliximab). In 54% of the patients the S had a chronic course and in 43% S remitted. Increased levels of ACE were associated with clinical remission of the disease and normal levels with chronicity (p: 0.013). Conclusion The results of our study resembles, in general, what has been published in the literature. In our study, elevated ACE is associated with remission of the disease, contrary to the published, in which increased levels of ACE in symptomatic patients may reflect disease activity. Disclosure of Interests None declared

Background: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia and a deficient production of specific antibodies. Almost 30% of patients with CVID develop an autoinmmune and granulomatous disease, similar to clinical and histological sarcoidosis (S), it affects the lung fundamentally. This can lead to a misdiagnosis of S in a patient with CVID, this leads to inadequate treatment and increases the morbidity and mortality of the disease. Objectives: Describe the clinical and radiological characteristics of a cohort of patients diagnosed with S with predominant pulmonary involvent. Make a study of immunoglobulin (IG) levels to see the frequency of CVID in these patients. Methods: Retrospective descriptive study of patients treated in our Hospital (2008-2018), with diagnosis of S. The data was obtained by reviewing medical records. The delay in the diagnosis of S was defined as the difference in months between the initial diagnostic suspicion and the final diagnosis of S. In patients with low levels IG, we have done and expanded ID study. Results: 55 patients (31 women) were included, with a mean age of 52 ±12 years. The initial diagnosis was: 85% S, 10% lymphoma and 4% tuberculosis. The median of months from the start of the clinic to the diagnosis of S was 5.5 months. Regarding the clinic, 21% patients present fever at the beginning of the disease, and 65% extrathoracic localization (cutaneous was the most frequent in 27%, and renal was the least frequent 5%). Simple x-ray and high resolution tomography of chest were done in all patients. Pulmonary stage 2 was the most frequent (51%), followed by stage 3 (16%), stage 0 (14%) and stage 4 (9%). In 90% of the patients, histological confirmation was obtained by transbronchial (47%), cutaneous (11%) or lymph node biopsy (29%). Igs were normal in 87% of patients, only 4 patients had low IG levels (Ig G in 3 patients and Ig M in 1). An extended ID study was performed in these 4 patients, being diagnosed with CVID 3 patients. Results of the 4 patients and the differential characteristics between CVID and S in table 1. Conclusion: Although their clinical presentation and histological appearance may be identical, the management of these two conditions is very different. The difficulties in the differential diagnosis between S and CVID, shows the importance of a history of screening for recurrent infections and the measurement of IG levels before the diagnosis of possible S. Disclosure of Interests: None declared

1Seville, Seville, Spain Background Assessment of pain improvement during treatment for Rheumatoid Arthritis (RA) may be useful to clinical decision between providers and their patients (pts). Baricitinib (BARI) once daily, an oral, selective Janus Kinase (JAK)1/JAK2 inhibitor, reduced disease activity levels in Rheumatoid Arthritis (RA) patients (pts) with an inadequate response (IR) to methotrexate (MTX). Objectives To Evaluate the likelihood of achieving different levels of pain control with BARI 2 mg or 4 mg in patients with RA with inadequate response to traditional DMARDs or biological DMARDs. Methods Prospective observational registry of pts with RA who start treatment with BARI, in a third level Spanish Hospital (October 2017- June 2018). BARI 2 mg is started in patients with inadequate response to traditional DMARDs and BARI 4 mg in patients with inadequate response to biological DMARDs. The pts were assessment of pain was assessed with 0-100 mm visual analog scale (VAS) at each study visit. The likelihood of achieving >=25%, >=50% and >=70% pain VAS improvement through week 12 and analyze if there are significant differences between the group of patients with BARI 2 mg and BARI 4 mg (Mann-Whitney test). The statistical study was carried out with the SPSS15 computer package. Results We included 38 pts (28 women), mean age 52 ± 12 years. Pain VAS improvement for all patients, baseline pain and weeks 12. The frequency is the percentage of improvement with respect to the baseline. In BARI 2 mg group, 58% of pts (p75) have experienced a decrease greater than pain VAS improvement than baseline and in BARI 4 mg group, 55% of pts (p75) have experienced a decrease greater than pain VAS improvement than baseline. No statistically significant differences were found in the two treatment groups (BARI 2 mg and BARI 4 mg) (p 0.847). Conclusion Our results, in general, agree with what is published in the literature (RA treated with BARI reported greater improvements in pain control when compared to adalimumab or placebo, a post-hoc analysis of the Phase 3 RA-BEAM study). BARI treated pts reported significantly greater and more rapid reductions in pain severity as measured by the pain VAS, improvements were sustained 12 weeks, without finding differences in pts receiving BARI 2 mg or BARI 4 mg. Disclosure of Interests None declared

Background: Immunotherapy has revolutionized the treatment of cancer. The use of checkpoints inhibitors aimed at stimulating the immune system to mediate regression of established malignant tumors has shown a noticeably increase in the last decade. However, immunotherapy has been associated with side effects novel to cancer patients such as immune-related adverse events (IAEs) that can affect any organ or system, either during the course of immunotherapy or once the treatment was completed. Objectives: To survey the occurrence and type of AAEs in 190 cancer patients treated with immunotherapy between 2011 and 2018. Methods: We surveyed the occurrence of IAEs in cancer patients who received immunotherapy in the Oncology Service at ‘Virgen del Rocio’ University Hospital (Seville, Spain) between 2011-2018. The types of cancer present in the patients analysed included: non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, kidney cancer, bladder cancer and others. The checkpoints inhibitors analysed included Ipilimumab (CTLA-4), Nivolumab (PD-1), Pembrolizumab (PD-1) and Atezolizumab (PD-L1). The nature of IAEs (rheumatic/non-rheumatic), the magnitude of complaint (mild/moderate/severe) and the outcome of patients depending on IAEs management was analysed. Finally, we used a multivariate analysis in search for patterns in IAE occurrence depending on cancer type, patient and treatment factors. Results: A total of 190 patients were collected, 143 men and 47 women having NSCLC (51.1%), melanoma (25.3%), kidney cancer (6.8%), bladder cancer (5.3%), SCLC (2.1%) and others. They received immunotherapy with Atezolizumab (15.8%), Ipilimumab (4.7%), Nivolumab (61.1%) and Pembrolizumab (18.4%). Overall, 28 patients (14%) developed an AAE secondary to immunotherapy. Four of them involved rheumatic diseases (1 seronegative polyarthritis, 1 inflammatory myopathy and 2 rheumatic polymyalgia), whereas other non-rheumatic diseases were observed: 13 endocrine (12 thyroiditis and 1 DM type I debut with ketoacidosis), 5 pulmonary (pneumonitis), 3 dermatological (2 atopic dermatitis and 1 psoriasis), 2 digestive (colitis and autoimmune pancreatitis) and 1 neurological (hypophysitis). The drug that showed the highest occurrence of IAEs was Nivolumab (30%). In these patients, IAEs were associated with a median number of cycles of 7 (Q1 = 4, Q3 = 17.7, non-parametric data, Shapiro-Wilk test, p Conclusion: Immunotherapy is changing the typology of side effects in cancer patients, including IAEs. The cases analysed showed a relatively small number of rheumatic events that were easily solved with corticosteroids (nor the immunotherapy treatment was suppressed or immunosuppressive treatment was necessary). The study highlights the benefits of involving multidisciplinary medical teams to manage oncologic patients treated with immunotherapy towards the early detection and treatment of IAEs. References [1] Michael A. Postow, M.D., Robert Sidlow, M.D., and Matthew D. Hellmann, M.D. Immune-Related Adverse Events Associated with Immune Checkpoint BlockadeN Engl J Med 2018; 378:158-168. DOI: 10.1056/NEJMra1703481 Disclosure of Interests: None declared

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease mediated by the immune system, which affects the musculoskeletal system and the skin. It is a disease with increased expression of TNF-alpha and IL23/IL17 cytokines, which are therapeutic targets whose neutralization has a great impact on the control of the disease. Ixekizumab is a monoclonal antibody inhibitor of IL-17 indicated for the treatment of moderate-severe psoriasis and PsA. Ixekizumab is administered subcutaneously every 4 weeks, and according to the latest studies, it is a well-tolerated drug and an effective treatment option with significant improvement in the quality of life of patients with cutaneous psoriasis and PsA. Objectives: -Describe the clinical characteristics, tolerance, safety and survival of a cohort of patients diagnosed with psoriasis or PsA, who have started treatment with Ixekizumab. -Correlate skin involvement and joint with the quality of life of the patient through the life questionnaire (DLQI) in patients treated with Ixekizumab. Methods: An observational, cross-sectional and retrospective study was conducted on a cohort of 29 patients who started treatment with Ixekizumab in our hospital in the last year (2018). The data were obtained through the review of patients’ medical records and through telephone contact to carry out quality of life questionnaires (DLQI). Results: Twenty-nine patients were included, of which 22 were males (79.5%). The mean age of the patients was 47 years. Of the cases included, 22 of the patients presented cutaneous Psoriasis (75.8%), 6 of the patients with PsA (20.7%) and 1 patient presented with Dermatomyositis antiMDA 5 (3.5%). Of the 29 patients included, 24 (82.2%) did not present adverse effects. Of the 5 patients who presented adverse effects, in 100% of the cases they were mild. All patients had received prior therapy with disease modifying drugs (DMARDs), and 31% were naive to biological therapy. A total of 4 patients required concomitant therapy with corticosteroid treatment, 3 of them with PAs and 1 with dermatomyositis anti MDA 5. The average of the DLQI of the patients analyzed was 4 and an average PASI of 1 after the start of the treatment, obtaining an Overall improvement of the skin. A statistically significant Pearson correlation of 0.895 was found between DLQI and PASI (dependent variable), with a strong degree of association. In which patients with a lower score in the DLQI had a lower PASI. Regarding the pain produced by the autoinjector, measured according to the EVA scale, it was 2 (mild pain), and none would abandon the treatment for this reason. Of all the patients, 9.1% abandoned the treatment due to inefficiency. Conclusion: The treatment with Ixekizumab presents some promising results in the treatment of cutaneous psoriasis and PsA. Treatment with Ixekizumab presents a significant improvement in the quality of life of patients. Ixekizumab is a well-tolerated drug with good efficacy in the short-medium term. It has also been shown to be a safe drug among the patients included in the study. However, long-term studies with a larger number of patients are required to evaluate the efficacy and safety of Ixekizumab. Disclosure of interests: None declared

Objective To describe disease-modifying antirheumatic drug (DMARD) patterns in routine clinical practice in adult rheumatoid arthritis (RA) patients and to ascertain the reasons for methotrexate (MTX) discontinuation. Methods A cross-sectional observational study was conducted from March to October 2014 at the Rheumatology Units of seven hospitals in Spain. In a single visit, the treating rheumatologist completed an online case report form. This report contained sociodemographic and RA variables. This study was conducted in accordance with Good Clinical Practice and local and national research legislations. Results A total of 301 patients (71% women) with a mean age of 56.7±14.0 years and disease duration of 3.6±1.5 years were examined. The patients had RA with moderate disease activity, at least one poor prognostic factor, and comorbidities. The mean time between RA diagnosis and prescription of the first conventional synthetic DMARD (csDMARD) was 2.4±6.0 months. A total of 295 patients (98%) started the first csDMARD on monotherapy. MTX was the most-prescribed first-line drug (n=233, 79%). The mean treatment time of the first-line csDMARD was 27.0±19.4 months. Of these patients, 98% progressed to a second-line csDMARD; 118 patients were changed to another DMARD, mainly due to inefficacy (51, 37%), adverse events (AEs, 37, 27%), or intolerance (18, 13%). The use of MTX as second-line therapy reduced from 79% to 51%. At the time of the study, 200 patients (66%) received a csDMARD as monotherapy and 45 (15%) a combination of ≥2 csDMARDs. Fifty-five (18%) patients were being treated with a biological drug in monotherapy (16, 29%) or in a combination with a csDMARD (39, 71%), mainly MTX, 147 patients (57%) received steroids. Biological DMARD were prescribed as the second line for 42% of patients and 51% of patients received the third-line therapy or beyond. The rate of AEs that motivated a change in the csDMARD was 34%. Conclusion MTX was the most-used csDMARD as first and second-line therapy together with corticosteroids. The combination of two or more csDMARDs as first-line treatment was very infrequent. MTX toxicity and intolerance were higher and more significant than inefficacy but progressively decreased with use.

Background:Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of Immunoglobulin-A vasculitis (IgAV) [1], an inflammatory vascular pathology.Interleukin (IL)17Ais a genetic risklocusfor autoimmune diseases, such as giant cell arteritis [2] and spondyloarthritis [3].Objectives:To determine the potential influence ofIL17Aon IgAV.Methods:FiveIL17Atag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and healthy controls were observed when eachIL17Agenetic variant was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the fiveIL17Apolymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIL17Awhen patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIL17Aon the pathogenesis of IgAV.References:[1]Autoimmun Rev 2018; 17: 301-15[2]Ann Rheum Dis 2014; 73: 1742-5[3]Mediators Inflamm 2018; 2018: 1395823.Acknowledgments:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Diego de Argila: None declared, Maximiliano Aragües: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: 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, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: 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

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

Objective (1) To analyse the implementation of multidisciplinary care models in psoriatic arthritis (PsA) patients, (2) To define minimum and excellent standards of care. Methods A survey was sent to clinicians who already performed multidisciplinary care or were in the process of undertaking it, asking: (1) Type of multidisciplinary care model implemented; (2) Degree, priority and feasibility of the implementation of quality standards in the structure, process and result for care. In 6 regional meetings the results of the survey were presented and discussed, and the ultimate priority of quality standards for care was defined. At a nominal meeting group, 11 experts (rheumatologists and dermatologists) analysed the results of the survey and the regional meetings. With this information, they defined which standards of care are currently considered as minimum and which are excellent. Results The simultaneous and parallel models of multidisciplinary care are those most widely implemented, but the implementation of quality standards is highly variable. In terms of structure it ranges from 22% to 74%, in those related to process from 17% to 54% and in the results from 2% to 28%. Of the 25 original quality standards for care, 9 were considered only minimum, 4 were excellent and 12 defined criteria for minimum level and others for excellence. Conclusions The definition of minimum and excellent quality standards for care will help achieve the goal of multidisciplinary care for patients with PAs, which is the best healthcare possible.

Background Peripheric Ulcerative Keratitis (PUK) is a severe inflammation that may lead to ocular perforation. PUK may be primary or associated with systemic conditions. Treatment is based on corticosteroids and conventional systemic immunosuppressive drugs. Objectives To evaluate biologic therapy in cases with severe and refractory PUK. Methods Multicenter study from 9 hospitals. Patients presented inadequate response or intolerance to conventional therapy with corticosteroids and at least 1 systemic traditional immunosuppressive drug. The main outcome measures were visual acuity, signs of inflammation, progression to corneal thinning, central keratolysis and ocular perforation. Comparisons were made between baseline and 1st week, 1st month, 6th month and 1st year. Statistical analysis was performed using the software STATISTICA (StatSoft). Results were expressed as mean±SD for variables with a normal distribution, or as median [IQR] when they were not normally distributed. The comparison of continuous variables was performed using the Wilcoxon test and categorical variables with chi-square test. Results We studied 27 patients/35 affected eyes (7 men/20 women), mean age, 57.2±16.3 years (range 28–89). PUK was primary in 1 case whereas in the 26 remaining cases, the underlying diseases were Rheumatoid Arthritis (RA) (n=19), Psoriasic Arthritis (n=2), RA+Felty syndrome+common variable immunodeficiency (n=1), Behcet Disease (n=1), Type I diabetes mellitus (n=1), granulomatous polyangiitis (n=1) and microscopic polyangiitis (n=1). They received the following topical therapy: corticosteroids (n=18), antibiotics (n=17), lubricants (n=18), autologous serum (n=11), topical cyclosporin 2% (n=11) and topical tacrolimus 0.03% (n=1). Besides oral corticosteroids and before the onset of the biologic therapy they had received iv pulses of methylprednisolone (n=8), methotrexate (16), oral doxycycline (9), azathioprine (3) and ascorbic acid (2). Moreover, 10 patients required surgery: amniotic membrane (n=7), penetrating keratoplasty (n=4), conjunctival resection (n=3), tissue adhesives (n=2), conjunctival flap (n=1) and lamellar keratoplasty (n=1). Anti-TNFα drugs were the most common biologic agents used in these cases (n=19): Adalimumab (ADA) (n=10; 37%), Infliximab (IFX) (n=8; 29.6%) and etanercept (n=1; 3.7%). In the remaining 8 cases the biologic agents were rituximab (n=7; 25.9%) and tocilizumab (n=1; 3.7%). The main outcome measures are summarized in the Table. After a mean follow-up of 23.7±20 months, all objective outcomes had improved with a reduction of the median prednisone dose from 33.7 [17.5–52.5] mg at baseline to 0 [0–2.5] mg (p=0.028). The main observed adverse effects were supraventricular tachycardia (n=1) and pulmonary Tuberculosis (n=1). Conclusions In our series, biological therapy, especially IFX and ADA, is effective and relatively safe in patients with PUK refractory to standard systemic treatment. 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

Objective Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. Methods This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. Results The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1–9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5–45) at the initiation of TCZ to 2.5 mg/day (IQR 0–30) at 12 months. After a median followup of 19 months (IQR 12–31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. Conclusion TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.

Objective To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Methods Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. Results A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis ( n = 8), psoriatic arthritis ( n = 6) and non-radiographic axial SpA ( n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate ( n = 13), sulfasalazine ( n = 6), pulses of methylprednisolone ( n = 4), azathioprine ( n = 3), leflunomide ( n = 2), and cyclosporine ( n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept ( n = 7), adalimumab ( n = 7), infliximab ( n = 6), and certolizumab ( n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy ( n = 7) or in combination with conventional immunosuppressive drugs ( n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0–0)] was significantly reduced compared to baseline findings [1 (0–3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. Conclusions Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis.

Resumen El uso de los glucocorticoides en la artritis reumatoide ha sido objeto de debate en las ultimas decadas. Parece existir evidencia probada, en cuanto a su capacidad antiinflamatoria y su poder de disminuir la progresion radiologica, principalmente si se utiliza en artritis reumatoide de inicio reciente. Sin embargo, sigue cuestionandose su uso debido a sus potenciales efectos secundarios, sobre todo cuando se utilizan en altas dosis y/o durante periodos prolongados. En esta revision, intentaremos resumir la evidencia existente sobre este aspecto desde los inicios, alla por los anos cincuenta del siglo xx , hasta las ultimas publicaciones.

The ideal therapy for lupus nephritis (LN) should reduce mortality. Although cyclophosphamide (CYC) has been used in the clinical setting for 30 years, the ability of this drug to achieve this goal is not supported by robust evidence. The first National Institutes for Health (NIH) trial in 1986 led to a shift from oral to intravenous (IV) CYC. The three NIH trials together then led to the dogma that high-dose IV CYC is the only cytotoxic agent superior to steroids alone in LN and to its general acceptance as the standard of care. Since then, high-dose IV CYC has been shown to have no impact on survival and to have a large number of adverse effects. The Euro-Lupus Nephritis Trial found that low-dose IV CYC could be used as an alternative to high-dose regimens and was associated with fewer secondary effects. Other studies have shown that other agents such as mycophenolate mofetil (MMF) have similar or even greater efficacy and a better safety profile. IV CYC is the only drug for which long-term data on LN is available. As evidence of other therapies such as MMF accumulates, however, IV CYC might no longer be considered the standard treatment for LN.

The use of glucocorticoids in rheumatoid arthritis has been the source of frequent debate in the last few decades. There is evidence on its anti-inflammatory capacity and its power to decrease radiologic progression, particularly if used in recent onset rheumatoid arthritis. However, there are still some voices questioning its use. Their arguments are its potential side-effects, especially when the glucocorticoids are used in high doses and/or for extended periods of time. In this review, we will try to summarize the evidence regarding this issue, from the beginning of the discussion in the fifties to the last releases.