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Objective: To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods: A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients’ association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. Results: Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. Conclusions: The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice., Este proyecto fue financiado por Merck Sharp & Dohme® España y avalado por las siguientes asociaciones/sociedades: CONARTRITIS (Coordinadora Nacional de Artritis asociación, de pacientes que representa a las personas afectadas por AR, APs, AIJ y EspA), OPENREUMA (Asociación de otros profesionales sanitarios dedicados a la reumatología) y SORCOM (Sociedad de Reumatología de la Comunidad de Madrid)

Resumen Objetivos Desarrollar recomendaciones sobre la actividad fisica y el ejercicio para pacientes con espondiloartritis (EspA) basadas en la opinion de expertos. Metodos Dos grupos de expertos, uno de fisioterapeutas, rehabilitadores y profesionales de la actividad fisica y deporte y otro de reumatologos con interes en EspA, se reunieron para discutir los resultados de grupos focales con pacientes sobre barreras al ejercicio y de una encuesta a reumatologos sobre ejercicio en EspA. A continuacion se redactaron unas recomendaciones preliminares que fueron sometidas a la opinion de los expertos de ambos grupos mediante metodologia Delphi a dos rondas. Resultados Se emitieron 21 recomendaciones que cubren el ejercicio fisico, la adaptacion al paciente, el modo de dar los mensajes, el manejo del dolor, el tipo de ejercicios indicado y el seguimiento. El grado de acuerdo varia ligeramente entre los grupos de expertos pero en general fue alto. Los items discordantes o con poco acuerdo fueron eliminados del consenso. Conclusiones Se han emitido recomendaciones sobre cuando y como prescribir ejercicio fisico y monitorizarlo en pacientes con EspA basadas en la opinion de expertos en espondilitis y en la prescripcion de ejercicio. Deberemos confirmar si estas recomendaciones son utiles para la practica clinica y tienen efecto en los pacientes con EspA atendidos por reumatologos.

Despite the evidence, there are doubts about the positioning of apremilast in the psoriatic arthritis (PsA) treatment algorithm. The objective of this project was to collect the scientific evidence and the experience of a group of rheumatologists who are experts in the management of PsA with apremilast in clinical practice in Spain.A scientific committee made up of 6 experts proposed 5 clinical scenarios where the evidence on the use of apremilast in PsA was controversial: (i) Efficacy in peripheral PsA; (ii) Efficacy in enthesitis and dactylitis; (iii) Efficacy in PsA with skin involvement; (iv) Comorbidities; and (v) Apremilast safety. After this, a panel of 17 rheumatologists with expertise in PsA management discussed these scenarios and generated a questionnaire with 50 questions and 156 items following the Delphi methodology. This questionnaire was anonymously answered by the panel.After 2 voting rounds, the panel of experts reached consensus in 93 of the 156 items raised (59.6%) (67 in agreement and 26 in disagreement). The degree of consensus was 53.3% in the area of "Efficacy in peripheral PsA"; 60.0% in "Efficacy in enthesitis and dactylitis"; 50.0% in "Efficacy in PsA with skin involvement"; 57.1% in "Management of comorbidities in patients with PsA"; and 67.3% in "Implications of safety in the use of apremilast".The structured opinion of the experts complements the available evidence and contributes to the establishment of consensual guidelines for the use of apremilast in PsA.

Resumen Objetivos Identificar las comorbilidades prioritarias en la espondiloartritis axial (EspAx) y recomendar como hacer su seguimiento desde una perspectiva eminentemente practica. Metodos Se selecciono a un grupo multidisciplinar (10 reumatologos [6 expertos en EspAx], 2 medicos de familia, una internista, una cardiologa, una gastroenterologa y una psicologa). En una primera reunion de discusion, se establecieron el alcance y los usuarios, y se voto una lista de comorbilidades sobre la base de la frecuencia y el impacto. Los panelistas debian defender con argumentos consistentes la inclusion de cada comorbilidad/item en el documento. Cuatro panelistas y 2 metodologos, desarrollaron revisiones sistematicas en temas controvertidos. En una segunda reunion se presentaron los resultados de las revisiones y los argumentos de todos los items a incluir. Tras esta reunion se redacto el documento final. Resultados El documento final incluye 2 listas de comprobacion (checklist), una para profesionales sanitarios y otra para pacientes, que recogen: riesgo cardiovascular, comorbilidad renal, riesgo gastrointestinal, estilo de vida, riesgo de infecciones y vacunacion, afectacion pulmonar, medicacion concomitante, trastornos psicoafectivos, osteoporosis y riesgo de fractura. Ademas, el documento refleja los argumentos para incluir cada item y la manera de recoger los items. Asimismo, el panel considero oportuno establecer unas «practicas a evitar» aplicables a la comorbilidad de la EspAx. Conclusiones Se generaron 2 listas de comprobacion y un listado de escenarios a evitar para facilitar el manejo de las comorbilidades de la EspAx. En pasos posteriores probaremos su utilidad y su aceptacion por un grupo amplio de usuarios que incluya medicos, pacientes y enfermeras.

The objective is to establish recommendations, based on evidence and expert opinion, for the identification and management of comorbidities in patients with psoriatic arthritis (PsA). The following techniques were applied: discussion group, systematic review, and Delphi survey for agreement. A panel of professionals from four specialties defined the users, the sections of the document, possible recommendations, and what systematic reviews should be performed. A second discussion was held with the results of the systematic reviews. Recommendations were formulated in the second meeting and voted online from 1 (total disagreement) to 10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation were assigned using the Oxford Centre for Evidence-Based Medicine guidance. The full document was critically appraised by the experts, and the project was supervised at all times by a methodologist. In a final step, the document was reviewed and commented by a patient and a health management specialist. Fourteen recommendations were produced, together with a checklist to facilitate the implementation. The items with the largest support from evidence were those related to cardiovascular disease and risk factors. The panel recommends paying special attention to obesity, smoking, and alcohol consumption, as they are all modifiable factors with an impact on treatment response or complications of PsA. Psychological and organizational aspects were also deemed important. We herein suggest practical recommendations for the management of comorbidities in PsA based on evidence and expert opinion.

Objective To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients’ association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. Results Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. Conclusions The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.

Background The impact of comorbidity on the diagnosis, prognosis, and treatment of rheumatic diseases could be very high. However, several studies have depicted a sub-optimal assessment of comorbidity in these diseases. Objectives To generate common, simple and practical support materials (checklists, questionnaires and other complementary materials) for rheumatologists, health professionals and patients, in order to: 1) Assess comorbidity; 2) Identify and implement preventive procedures; 3) Define referral criteria to other health professionals, in patients with rheumatoid arthritis (RA), axial spondylitis (axSpA), and psoriatic arthritis (PsA). Methods This project was promoted by CONARTRITIS (Association of patients with arthritis), OPENREUMA (Multidisciplinary association of professionals dealing with patients with rheumatic diseases) and SORCOM (Rheumatology Society of the Madrid Region). A multidisciplinary team specialized in comorbidity in inflammatory arthritis was established (6 rheumatologists, 2 primary care physicians, 2 nurses, 1 internist, 1 psychologist). A qualitative study was performed following these phases: 1) Review of the GECOAR1, GECOAX2 and GECOAP3 projects, that were focus on the evaluation of comorbidity in RA, axSpA and PsA, as well as an exhaustive bibliographic search in Medline; 2) Generation of preliminary checklists (different versions and formats) to be used by health professionals and patients for the identification, management and prevention of comorbidity; 3) Patient focus group in which the preliminary patients checklist was evaluated and discussed; 4) Nominal group meeting in which the selected health professionals analyzed all the checklists and modified them taking into account the opinion of the patients; 5) External evaluation of the modified checklists by patients, health professionals and rheumatologists, all of them outside the project; 6) Generation of the final checklists based on everything collected in the previous phases. Results Three checklists for clinical practice were designed, two for health professionals (one to identify comorbidity, another on prevention/health promotion), one for patients. The comorbidity checklist includes, for example, the evaluation of cardiovascular risk factors, depression and anxiety, allergies or infections. The prevention checklist includes life style issues (smoking, diet, exercise), social life, sexuality, sleep, or oral hygiene. The checklists also specify the evaluation method (questions, specific questionnaire, etc.). Conclusion The use of specific checklists for the identification, management and prevention of comorbidity inpatients with RA, axSpA and PsA might contribute positively in their prognosis. References [1] Loza E, et al. Rheumatol Int. 2015 Mar;35(3):445-58. [2] Gonzalez C, et al. Reumatol Clin. 2018 Nov - Dec;14(6):346-359. [3] Torre-Alonso JC, et al. Rheumatol Int. 2017 Aug;37(8):1239-1248. Disclosure of Interests Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Carlos M. Gonzalez: None declared, Maria del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Silvia Garcia-Diaz: None declared, Juan Carlos Hermosa: None declared, Cristina Lajas: None declared, Leticia Leon: None declared, Juan Carlos Obaya: None declared, Maria Rodero: None declared, Carmen Suarez: None declared, Virginia Villaverde: None declared, Juan Carlos Torre-Alonso: None declared

Background: In the last years multiple genetic variants have been associated with autoimmune disease (AD) risk. However, much less is known on the association with important environmental factors like diet. Objectives: The objective of the present study is to characterize the dietary patterns of six prevalent ADs, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE). Methods: A cross-sectional cohort of 11,621 individuals from Spain encompassing 1,949 RA, 2,186 psoriasis (PS), 1,437 PsA, 699 SLE, 1,415 ulcerative colitis (UC), 1,952 Crohn’s disease (CD) and 1,983 healthy controls, was recruited by the IMID-Consortium. The weekly consumption frequency of main food categories was recorded, together with drinking habits and smoking status. Multivariate linear models were used to test for association while adjusting for confounders. Results: Patients with AD targeting the digestive system showed the largest differences in comparison to controls. In the rheumatic ADs several food categories were also found to be consumed differently compared to controls. SLE had a high consumption of sweets and pastries, and RA ate more fruit and bread/wholegrain foods and less meat and cold cuts compared to controls. In PsA the dietary pattern differences with controls where milder, and non-overlapping with psoriasis. Disease activity was significantly associated with specific food categories in CD, UC and PS, mildly in RA and SLE, and PsA showed no association. High smoking cessation rates were observed in UC, CD and SLE, but not in Ps, RA and PsA. Tea/coffee and alcohol consumption was low in all ADs compared to controls. Conclusion: Our results show previously unreported associations with dietary habits in rheumatic ADs. Disclosure of Interests: Antonio Julia: None declared, Sergio Hilario Martinez: None declared, Jesus Tornero: None declared, Juan D. Canete: None declared, Antonio Fernandez-Nebro: None declared, Francisco Blanco: None declared, Jesus Rodriguez: None declared, Francisco J Lopez-Longo: None declared, Benjamin Fernandez-Gutierrez: None declared, Jordi Gratacos: None declared, Jose Javier Perez Venegas: None declared, Carolina Perez: None declared, Ruben Queiro Silva: None declared, Alejandro Olive: None declared, Mercedes Alperi-Lopez: None declared, Carlos A. Montilla-Morales: None declared, Jose Luis Andreu: None declared, Juan Carlos Torre-Alonso: None declared, M Angeles Aguirre-Zamorano: None declared, Hector Corominas: None declared, Paloma Vela Casasempere: None declared, Victor Martinez Taboada : None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Joan Miquel Nolla: None declared, Isidoro Gonzalez-Alvaro: None declared, Santiago Munoz-Fernandez: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen, Carlos M. Gonzalez: None declared, Antonio Zea: None declared, Maria Lopez Lasanta: None declared, Daniel Roig: None declared, Jose M Pego-Reigosa: None declared, Mireia Lopez Corbeto: None declared, Pedro Zarco-Montejo: None declared, Mercedes Freire Gonzalez: None declared, Alba Erra: None declared, Elvira Diez Alvarez: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Esther Rodriguez Almaraz: None declared, Alicia Garcia: None declared, Patricia Carreira: None declared, GEORGINA SALVADOR ALARCON: None declared, Cesar Diaz Torne Consultant for: Grunenthal, Speakers bureau: Grunenthal, Ricardo Blanco: None declared, Alfredo Willisch Dominguez: None declared, Jose Antonio Mosquera Martinez: None declared, Simon Sanchez Fernandez: None declared, Julio Ramirez: None declared, Sara Marsal: None declared

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

To develop and evaluate a web application based on multimedia animations, combined with a training program, to improve the prescription of exercises in spondyloarthritis (SpA). After a review of exercises included in the main clinical trials and recommendations of international societies, a multidisciplinary team—rehabilitators, rheumatologists, physiotherapists, computer scientists and graphic designers—developed a web application for the prescription of exercises (EJES-3D). Once completed, this was presented to 12 pairs of rehabilitators–rheumatologists from the same hospital in a workshop. Knowledge about exercise was tested in rheumatologists before and 6 months after the workshop, when they also evaluated the application. The EJES-3D application includes 38 multimedia videos and allows prescribing predesigned programs or customizing them. A patient can consult the prescribed exercises at any time from a device with internet connection (mobile, tablet, or computer). The vast majority of the evaluators (89%) were satisfied or very satisfied and considered that their expectations regarding the usefulness of the web application had been met. They highlighted the ability to tailor exercises adapted to the different stages of the disease and the quality and variety of the videos. They also indicated some limitations of the application and operational problems. The EJES-3D tool was positively evaluated by experts in SpA, potentially the most demanding group of users with the most critical capacity. This allows a preliminary validation of the contents, usefulness, and ease of use. Analyzing and correcting the errors and limitations detected is allowing us to improve the EJES-3D tool.

Juan Carlos Torre-Alonso,1 Rubén Queiro,2 Marta Comellas,3 Luís Lizán,3,4 Carles Blanch5 1Rheumatology Department, Faculty of Medicine and Health Sciences, University of Oviedo, Hospital Monte Naranco, Oviedo, Spain; 2Rheumatology Division, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain; 3Outcomes 10, Castellón de la Plana, Spain; 4Medicine Department, Jaime I University, Castellón de la Plana, Spain; 5Health Economics & Market Access, Novartis Pharmaceuticals, Barcelona, Spain Objective: This review aims to summarize the current literature on patient-reported outcomes (PROs) in spondyloarthritis (SpA). Patients and methods: We performed a systematic literature review to identify studies (original articles and narrative and systematic reviews) regarding PROs (health-related quality of life [HRQoL], satisfaction, preferences, adherence/compliance, and persistence) in SpA patients published in the European Union through December 2016. International databases (Medline/PubMed, Cochrane Library, ISI Web of Knowledge, Scopus) were searched using keywords in English. The methodological quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine criteria. Results: A total of 26 publications met the inclusion criteria. Generally, studies indicated that SpA has a negative impact on patients’ HRQoL. In patients with ankylosing spondylitis, physical domains were more affected than emotional ones, whereas for psoriatic arthritis, both physical and psychological factors were strongly affected by the disease. Data indicated that biological agents (BAs) greatly contributed to improvement in HRQoL in both ankylosing spondylitis and psoriatic arthritis patients. Findings on compliance with BAs were heterogeneous. However, persistence rates exceeded 50% irrespective of the BA administered. Results on preferences indicated that most SpA patients prefer being involved in decisions regarding their treatment and that besides efficacy and safety, frequency and route of administration may influence patients’ preferences for BAs. Conclusion: Implementing management programs for SpA patients focuses on the physical, emotional, and social consequences of the disease, in addition to assessing and including patient preferences in the treatment decision-making process, could be crucial to improve patients’ HRQoL and ensure their satisfaction and compliance with treatment. Keywords: spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, patient-reported outcomes, European Union, systematic review

Objective The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panellists for a rational use of synthetic disease modifying antirheumatic drugs (DMARDs) and biologicals in psoriatic arthritis (PsA) patients. The present document also focuses on important aspects in the management of PsA, such as early diagnosis, therapeutic objectives, comorbidities and optimisation of treatment. Methods The recommendations were agreed by consensus by a panel of 8 expert rheumatologists, previously selected by the Spanish Society of Rheumatology (SER) through an open call. The phases of the work were: identification of key areas for updating the previous consensus, analysis and synthesis of scientific evidence (modified Oxford system, Centre for Evidence-based Medicine, 2009) and formulation of recommendations based on this evidence and by consensus techniques. Results Seventeen recommendations were issued for the treatment of PsA patients. Six of them were of general nature, ranging from the early diagnosis and treatment to the importance of assessing comorbidities. The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease. Likewise, the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included. Conclusions We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics.

Background PsA has a higher heritability than PsV, indicating the existence of additional PsA-specific genetic factors. To date, however, the specific genetic basis underlying PsA is poorly understood. Objectives The objective the present study was to identify new genetic variation specifically associated with PsA risk. Methods In order to characterize the genetic basis of PsA, we performed a GWAS meta-analysis at the single-marker level as well as at the pathway level (GWPA). A cohort of 835 PsA patients and 1,558 controls from the Spanish population was genotyped for >550,000 SNPs. GWAS data from a second cohort of 1,430 PsA patients and 1,417 controls from the North American population was also used. In order to confirm the specificity of the new genetic variation associated with PsA risk, we analyzed the association with purely cutaneous psoriasis (PsC, n=614) and rheumatoid arthritis (RA, n=1,191). We performed a pharmacogenetic analysis to investigate the new PsA-specific pathways as a source for drug discovery in PsA. Results GWAS meta-analysis identified a new association between B3GNT2 gene and PsA (P Conclusions The present study represents an important step towards the characterization of the genetic factors specific to PsA risk. Disclosure of Interest None declared

Background During the development of recommendations and implementation aids of the GECOAx project, the importance of avoiding certain situations was highlighted. Objectives To recognize what prescriptions, risk assessments, or preventive strategies are wrong practices and should thus be avoided in clinical practice. To establish not to do recommendations in the management of the comorbidity of AxSpA. Methods A multidisciplinary group was selected [10 rheumatologists, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 2 family physicians]. With the support of 3 methodologists, and after interactions aimed to edit a document for the management of comorbidity launched by the same panel, a list of Not to do recommendations was issued. In a discussion meeting, evidence was provided to support the recommendations, items without sufficient basis were removed, and the final list was produced. Results A summary list of Not to do recommendations (Table 1) was issued. Conclusions These recommendations aim to avoid making common mistakes in clinical practice and to help better management of frequent comorbidity in patients with AxSpA. Acknowledgements This project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the manuscript. Disclosure of Interest None declared

Background The management of comorbidity in patients with axial spondyloarthritis (Ax-SpA) needs improvement; the implementation of clinical practice guidelines is still deficient and heterogeneous. Objectives To prioritise comorbidities in Ax-SpA and to elaborate practical aids for their identification and follow-up. Methods A multidisciplinary panel [10 rheumatologists (6 experts in Ax-SpA), 2 family doctors, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 3 methodologists] prioritised, in a discussion group, a list of comorbidities based on frequency and impact. Each comorbidity was discussed largely and systematic reviews were performed to support or discard items. In a second meeting, items to be included were presented, discussed, and those with lower priority disregarded. Results The panel produced a checklist for health professionals and another for patients. Each item is supported by arguments and references. Table 1 shows, schematically, the items included in the checklists. Conclusions These checklists are intended to facilitate the systematic evaluation of co-morbidity associated with Ax-SpA, thus allowing an earlier detection and better control and management of these patients by the rheumatologist. Acknowledgements This project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the abstract. Disclosure of Interest None declared

Aim: Variation at PDE3A-SLCO1C1 locus has been recently associated with the response to anti-TNF therapy in rheumatoid arthritis. We undertook the present study to determine whether PDE3A-SLCO1C1 is also associated with the response to anti-TNF therapy in psoriatic arthritis. Patients & methods: Genomic DNA was obtained from 81 psoriatic arthritis patients that had been treated with anti-TNF therapy. PDE3A-SLCO1C1 SNP rs3794271 was genotyped using Taqman realt-time PCR. The clinical response to anti-TNF therapy was measured as the change from baseline in the level of disease activity according to the DAS28 score. Results: A significant association between rs3794271 and anti-TNF response in psoriatic arthritis was found (beta = -0.71; p = 0.0036). Conclusion: PDE3A-SLCO1C1 locus is also associated with response to anti-TNF therapy in psoriatic arthritis. Original submitted 12 May 2014; Revision submitted 18 August 2014

a b s t r a c t Objectives: Improving referral of patients with back pain to rheumatologists could accelerate the diagnosis of axial spondyloarthritis. The RADAR study compared two strategies in the referral of patients with chronic back pain (> 3 months) with an onset before the age of 45 years from primary care centers to rheumatology departments, in relation to the diagnosis of axial spondyloarthritis. Patients and methods: Each primary care center was assigned a referral strategy for its patients: (a) strategy 1, patients who had one of the 3 following criteria: inflammatory back pain, HLA-B27 positivity or sacroiliitis in imaging; or (b) strategy 2, patients who had 2 of the following 6: inflammatory back

Resumen Objetivo Establecer las caracteristicas diferenciales segun el sexo y el tiempo de evolucion de la enfermedad en aquellos pacientes diagnosticados de espondilitis anquilosante (EA) asistidos en consultas de reumatologia de toda Espana, incluidos en el Registro Espanol de Espondiloartritis (REGISPONSER), asi como la repercusion diagnostica y terapeutica que ello conlleva. Pacientes y metodos Estudio transversal y observacional de 1.514 pacientes con EA seleccionados de entre 2.367 con espondiloartritis incluidos en REGISPONSER. En cada paciente se evaluaron y registraron de modo exhaustivo los datos demograficos, epidemiologicos, sociosanitarios, clinicos, analiticos, radiologicos y terapeuticos previstos en el protocolo de REGISPONSER que componen el Conjunto Minimo Basico que identifica la enfermedad. La funcion fisica se evaluo mediante «Bath Ankylosing Spondylitis Functional Index». La actividad clinica mediante velocidad de sedimentacion globular, proteina C reactiva y «Bath Ankylosing Spondylitis Disease Activity Index» (BASDAI). A cada paciente se le realizaron radiografias anteroposterior de pelvis, anteroposterior y lateral de columna lumbar y lateral de columna cervical, y se puntuaron segun el indice «Bath Ankylosing Spondylitis Radiographic Index Spine» (BASRI-Spine), que mide el dano estructural. Resultados De los 1.514 pacientes seleccionados, 1.131 (74.7%) eran hombres. Encontramos que existen diferencias significativas en la edad tanto al inicio de los sintomas como en el dia de la inclusion entre ambos grupos, siendo menor en los hombres. Tambien obtuvimos diferencias en el tiempo de evolucion de la enfermedad, que fue menor en el grupo de las mujeres. En cuanto a la existencia de antecedentes de EA entre los familiares de primer grado, las formas familiares fueron mas frecuentes entre las mujeres, tambien resulto superior en estas la puntuacion media del BASDAI, con independencia del tiempo de evolucion. Por el contrario, la mejoria del dolor con la toma de antiinflamatorios no esteroideos fue mayor en el caso de los hombres, asi como la severidad radiologica, ambas de forma significativa. Conclusiones Entre los pacientes con EA espanoles existen algunas diferencias en las manifestaciones clinicas y cuando se controlo segun el tiempo de evolucion, tambien encontramos diferencias radiologicas segun el sexo; los hombres muestran mas dano estructural, mientras que las mujeres presentan mayor actividad. Estos datos sugieren que el fenotipo de EA difiere entre generos, lo que puede influir en el manejo diagnostico y posterior eleccion terapeutica.

Objectives To identify priorities among comorbidities in axial spondyloarthritis (AxSpA) and recommend how to follow them from an eminently practical perspective. Methods A multidisciplinary group was selected (10 rheumatologists—6 of them experts in AxSpA—, 2 general practitioners, an internist, a cardiologist, a gastroenterologist and a psychologist). In a first discussion meeting, the scope and users were established and a list of comorbidities was voted based on frequency and impact. The panellists had to defend the inclusion of each comorbidity/item in the document with consistent arguments. Four panellists and two methodologists developed systematic reviews on controversial topics. In a second meeting, the results of the reviews and the arguments concerning the items to be included were presented. After the meeting, the final document was drafted. Results The final document includes two checklists, one for health professionals and another for patients; they incorporate cardiovascular risk, renal comorbidities, gastrointestinal risk, lifestyle, risk of infections and vaccinations, pulmonary involvement, concomitant medication, psycho-affective disorders, osteoporosis, and risk of fracture. In addition, the document reflects the arguments favouring the inclusion of each item and how to record the items for subsequent collection. The panel considered it also appropriate to likewise establish «practices to avoid» applicable to comorbidity in AxSpA. Conclusions Two checklists and a list of situations to avoid were generated to facilitate the management of comorbidities in AxSpA. In a future step, their utility and acceptance will be tested by a broad group of users that includes doctors, patients and nurses.

Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS.Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit.A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate.High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.

Several classification criteria for psoriatic arthritis have been proposed in the literature but it is still unclear which one of them best represents the diseases' ample spectrum. None of these classification criteria have been universally accepted. New classification criteria (CASPAR) have been recently published. Their application is simple, fast and easy to perform. In addition, they show two important qualities. One is that they allow for the diagnosis of psoriatic arthritis even when there is no skin disease present at the moment of diagnosis. The other is is that it enables us to classify a patient as having psoriatic arthritis in spite of a positive rheumatoid factor. The CASPAR criteria have a sensitivity of 91.4% and a specificity of 98.7%. It seems, in contrast, that it is not as high for recent-onset psoriatic arthritis. Therefore establishing the definition of inflammatory arthritis becomes paramount.

OBJECTIVE To evaluate the therapeutic effectiveness of reducing the infliximab dose interval to 6 weeks in spondyloarthropathy patients not responding to 5 mg/kg every 8 weeks. METHODS After 30 weeks of infliximab therapy, 25 patients were classified as responders [Bath Ankylosing Spondylitis Activity Index (BASDAI)

To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors involved in psoriatic arthritis (PsA).DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequence-specific oligonucleotide probes to determine HLA-C. To examine whether MICA (class I major histocompatibility complex chain-related gene A) confers additional susceptibility, trinucleotide repeat polymorphism in the transmembrane region of the MICA gene was investigated by radioactive PCR. Further analysis of MICA was made by PCR-single-strand conformational polymorphism to determine the allelic variant corresponding to MICA transmembrane polymorphism.Our results reveal new findings: 1) the frequency of the Cw*0602 allele was significantly increased in both patient groups: psoriasis (corrected P [Pcorr]10(-5), relative risk [RR] 6.2), PsA (Pcorr10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a significantly higher frequency in PsA patients (Pcorr0.00035, RR 3.2), whereas a similar distribution was found in both the control and psoriasis population, 3) this polymorphism corresponds to the MICA-002 allele and was found to be overrepresented in patients with the polyarticular form (Pcorr0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independent of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributable to 1 allele when the relative risk is1) in PsA patients who carry Cw*0602.The data obtained in this study are consistent with the polygenic inheritance of psoriasis. Cw*0602 appears to be the stronger genetic susceptibility factor for psoriasis. Independent of the HLA-C association, MICA-A9 polymorphism corresponding to the MICA-002 allele is a possible candidate gene for the development of PsA.

Background Genome-wide association studies (GWAS) in Psoriatic Arthritis (PsA)patients and controls have allowed the identification of multiple variants associated with disease risk. To date, however, no GWAS for PsA phenotypes has been reported. Objectives The main objective of this study was to identify new genetic variation associated with clinical phenotypes in PsA. Methods A total of n=835 patients diagnosed with PsA using CASPAR criteria were recruited in the discovery stage and genotyped for >600,000 single nucleotide polymorphisms. GWAS were performed for clinical and biological phenotypes associated with joint and skin disease. After allelic association analysis, those SNPs with highest level of significance were analyzed in an independent cohort of n=414 PsA patients. Results In the GWAS stage, several genomic regions showing high evidence of association with different PsA phenotypes (P Conclusions Usign a GWAS approach, new loci associated with axial and peripheral disease in PsA have been identified. Disclosure of Interest None declared

Background Psoriatic disease (PsD) is associated with multiple comorbidities. When establishing management protocols, the periodicity for detection and evaluation of such comorbid conditions needs to be specified. Objectives To establish guidelines for the follow-up of selected comorbidities in patients with PsD. Methods An expert panel with specialists in Rheumatology, Internal Medicine, Dermatology and General Practitioners defined the comorbidities with higher impact on PsD based on the existing literature and their experience. The periodicity for detection and monitoring of comorbidities in the Rheumatology setting was established by consensus after iterations and systematic review. Results The expert panel agreed to evaluate comorbidities as part of routine clinical practice at the time of diagnosis, upon changes in systemic treatment and at follow-up visits (evidence level 5, level of agreement 8.8). In any case, monitoring must be customized depending on the risk profile, morbidity, comorbidities and patient preferences. The following table shows the proposed periodicity for detection, assessment, and monitoring of the most important comorbidities in PsD. Conclusions This proposal for a periodic assessment of comorbidities in patients with PD allows systematic clinical monitoring of the patient by the Rheumatologist and Dermatologist, and can contribute to the early detection and management of these comorbidities Acknowledgement The GECOAP project was funded by Merck Sharp & Dohme of Spain Disclosure of Interest None declared

Objectives To establish recommendations for the management of comorbidities in patients with psoriatic disease (PsD). Methods A multidisciplinary panel drafted the recommendationsin a nominal group session. Evidence from four systematic reviews was added. Agreement was assessed by two-rounds Delphi technique. Recommendations with an agreement ≥7/10 by at least 70% of participants were kept in. Results A total of 19 recommendations on three key topics were issued: 1) screening of specific comorbidities, 2) specific preventive or therapeutic actions, and 3) general management. Conclusions Disease control coupled with the management of comorbidities is critical to ensure optimal patient care. These recommendations suggest actions on detection, management and integration of care in PsD. Acknowledgement GECOAP project was funded by Merck Sharp & Dohme of Spain Disclosure of Interest None declared

Improving referral of patients with back pain to rheumatologists could accelerate the diagnosis of axial spondyloarthritis. The RADAR study compared two strategies in the referral of patients with chronic back pain (3 months) with an onset before the age of 45 years from primary care centers to rheumatology departments, in relation to the diagnosis of axial spondyloarthritis.Each primary care center was assigned a referral strategy for its patients: (a) strategy 1, patients who had one of the 3 following criteria: inflammatory back pain, HLA-B27 positivity or sacroiliitis in imaging; or (b) strategy 2, patients who had 2 of the following 6: inflammatory back pain, HLA-B27 positivity, sacroiliitis in imaging, family history of axial spondyloarthritis, extra-articular manifestations or good response to nonsteroidal antiinflammatory drugs. The rheumatologist established the final diagnosis.Eighty-eight Spanish patients (mean age 36.8 years [SD 8.7], 55.7% females and 44.3% males) were referred for evaluation, 60 patients under strategy 1 and 28 under strategy 2. A definitive diagnosis of axial spondyloarthritis was established in 25.4% with strategy 1 and in 28.6% with strategy 2 (p=NS). Inflammatory back pain was the criterion most commonly used for referral, and the agreement rate between the primary care physician and rheumatologist was 75%.A simple referral strategy based on one of three3 criteria proved as effective as a strategy based on two of 6 criteria in diagnosing axial spondyloarthritis. Inflammatory back pain was the criterion most commonly used for patient referral.

Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.

To describe the differential characteristics by gender and time since disease onset in patients diagnosed with ankylosing spondylitis (AS) attending the Spanish rheumatology clinics, including those on the "Spanish Registry of spondyloarthritis" (REGISPONSER), as well as the diagnostic and therapeutic implications that this entails.This is a transversal and observational study of 1514 patients with AS selected from 2367 spondyloarthritis cases included in REGISPONSER. For each patient, the demographics, epidemiology, geriatric, clinical, laboratory, radiological, and therapeutic aspects were were evaluated and comprehensively recorded under the aegis of REGISPONSER, constituting the Minimum Basic identifying data for the disease. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical activity was evaluated using erythrocyte sedimentation rate, C reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Each patient underwent pelvic anteroposterior, anteroposterior and lateral lumbar spine as well as lateral cervical spine x rays; they were scored according to the Bath Ankylosing Spondylitis Spine Radiographic Index, which measures structural damage.Of the 1514 patients screened, 1131 (74.7%) were men. We found significant differences in age at onset of symptoms as well as in the day of inclusion, between the two groups, being lower in men. We also obtained differences in the duration of the disease, which was lower in women. As for the existence of a history of AS among first-degree relatives, family forms were more common among women. The mean BASDAI score was also higher in women, regardless of time since onset of disease. In contrast, the improvement of pain with the use of NSAID's and radiological severity were higher in men, both reaching statistical significance.Among the Spanish AS patients, there are some differences in the clinical manifestations, even when the time since onset of disease was controlled; we also found radiological differences by gender; men showing more structural damage, while women were more active. These data suggest that the phenotype of AS differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.

Objective To investigate the potential association of major histocompatibility complex (MHC) markers other than HLA–B27 with ankylosing spondylitis (AS). Methods A total of 603 patients with AS and 542 healthy control subjects, all of whom were HLA–B27 positive, were selected for this study based on clinical criteria. First, high-density genotyping across the MHC region (2,360 single-nucleotide polymorphisms [SNPs]) was performed in a cohort of 191 patients and 241 control subjects. After a fine-mapping study, 5 SNPs from the HLA–DPA1/DPB1 region were validated in a second cohort of 412 patients with AS and 301 healthy control subjects. Results Seventeen SNPs located within or near the HLA–DPA1 and HLA–DPB1 loci showed association with AS (P = 1.38 × 10−5 to 0.05). In addition, multimarker tests, both linkage disequilibrium and sliding windows, showed association of some groups of adjacent SNPs within the HLA–DPA1/DPB1 region with AS (P = 1.0 × 10−4 to 3.96 × 10−7). We validated the association by genotyping 5 SNPs from the DPA1/DPB1 region in an additional cohort and obtained P values from 6.42 × 10−5 to 0.01 in the analysis of the combined cohorts. Subtyping analysis of HLA–DPA1 and HLA–DPB1 showed that HLA–DPA1*01:03, A1*02:01, and B1*13:01 were the subtypes most susceptible to AS. Conclusion HLA markers and linkage disequilibrium blocks near HLA–DPA1 and HLA–DPB1 are statistically associated with AS. We identified a region located around the HLA–DPA1 and HLA–DPB1 loci associated with AS, another region within the MHC that is different from HLA–B27.

Objective.Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the axial skeleton and characterized by ossification of the spinal disc, joints, and ligaments leading to progressive ankylosis. Vertebral osteoporosis is a recognized feature of AS. Studies have confirmed a moderate to high prevalence of vertebral fractures with extremely varying ranges in patients with AS. Our objective was to estimate the prevalence of vertebral fractures in a representative Spanish population of patients with AS using a validated semiquantitative method, MorphoXpress®.Methods.Patients were randomly selected from the 10 initial participating centers of the Spanish National Registry of Spondyloarthropathies (REGISPONSER) by consecutive sampling. All patients fulfilled the New York modified criteria for AS and had a baseline thoracolumbar radiograph. A prevalent vertebral fracture was defined according to the Genant classification criteria.Results.The estimated prevalence of vertebral fractures was 32.4% (95% CI 25.5%–39.3%). The majority of fractures were localized in the thoracic segment (n = 100; 82.%) and were mild (n = 79; 64.8%). In logistic regression analysis, age (odds ratio per year 1.05, 95% CI 1.03–1.08, p < 0.001), disease duration (OR per year 1.03, 95% CI 1.01–1.06, p = 0.011), Bath Ankylosing Spondylitis Functional Index score (OR per score 1.16, 95% CI 1.03–1.30, p = 0.015), Bath Ankylosing Spondylitis Radiographic Index-TS (OR per score 1.25, 95% CI 1.12–1.39, p < 0.001), and wall-occiput distance (OR per cm 1.15, 95% CI 1.08–1.23, p < 0.001) were all associated with prevalent fracture.Conclusion.Semiquantitative methods are needed to improve the diagnosis of vertebral fractures in AS in order to start early treatment and to avoid complications arising from osteoporosis.

Several classification criteria for psoriatic arthritis have been proposed in the literature but it is still unclear which one of them best represents the diseases' ample spectrum. None of these classification criteria have been universally accepted. New classification criteria (CASPAR) have been recently published. Their application is simple, fast and easy to perform. In addition, they show two important qualities. One is that they allow for the diagnosis of psoriatic arthritis even when there is no skin disease present at the moment of diagnosis. The other is is that it enables us to classify a patient as having psoriatic arthritis in spite of a positive rheumatoid factor. The CASPAR criteria have a sensitivity of 91.4% and a specificity of 98.7%. It seems, in contrast, that it is not as high for recent-onset psoriatic arthritis. Therefore establishing the definition of inflammatory arthritis becomes paramount.

The national registry of spondyloarthropathies (REGISPONSER) is launched to classify patients with this group of diseases treated in Spanish rheumatology clinics. This manuscript describes the methodological and organizational background as well as characteristics of patients finally included, and provides a comparative analysis between characteristics of both ankylosing spondylitis and undifferentiated spondyloarthropathy groups of patients.Twelve members of the GRESSER group have participated in the registry, for a one-year recruitment period. All consecutively registered adult patients treated in their clinics met the classification criteria of the European Spondyloarthropathies Study Group (ESSG). Data collected reflect the socio-demographic characteristics, as well as disease activity and functional status, clinical form at onset, treatment used and quality of life; all measured by standard instruments.Throughout 1 yr, 1385 patients have been included in the registry: 939 males (68%) and 440 females (32%), with an average age of 47 +/- 13 years (mean +/- s.d.), and an average disease duration of 12 +/- 9 years. Diagnoses of the included patients were: AS (n = 842, 61%), PsA (n = 290, 21%), u-SpA (n = 205, 15%), reactive arthritis (n = 16, 1.2%), inflammatory bowel disease arthritis (n = 13, 0.9%) and JCA-spondyloathropathy (n = 13, 0.9%). Regarding clinical form, 54% had axial disease, 20% peripheral disease, 24% mixed disease and 0.6% isolated enthesitic form. Low-back pain was the first symptom reported in 53% of the patients, and most common extra-articular disease manifestations were psoriasis (25%), anterior uveitis (16%) and intestinal inflammatory disease (4%). Some kind of work disability was reported by 353 patients (25.5%).Such databases are very useful to obtain information about characteristics of SpA patients treated in a certain location or following a specific treatment practice, and provide a tool for assessing the impact of the disease. Data collected in this registry provide an appropriate clinical and demographic profile of patients suffering from SpA in Spain.

Background Rheumatoid arthritis (RA) is a complex disease of unknown etiology, involving both genetic and environmental factors. Objectives The aim of this study was to analyze the more relevant epidemiological characteristics in a large cohort of patients with RA and controls in the Spanish population. Methods A cross-sectional,comparative,multicenter study of patients with RA and hypernormal healthy subjects for IMID diseases was performed.All patients were recruited through the Immune-Mediated Inflammatory Diseases Consortium (IMIDC).The IMIDC is a network of Spanish biomedical researchers focused in the study of the molecular basis of IMID diseases.All patients included in the present study were selected from the outpatient clinics of 12 Rheumatology Departments at different Spanish university hospitals.An epidemiological questionnaire developed by experts at DNA National Bank was applied to obtain all data. Results 2,366 RA patients and 1,558 healthy subjects were included.77% of RA patients and 40% of controls were female.The mean age of patients with RA was 60±13 years and controls 49±7 years.The height and weight of controls was significantly higher than in patients with RA.The level of statistical significance was decreased by introducing gender and age as covariates.In our cohort,65% of patients with RA had no education or only primary education.Control subjects mostly had secondary or higher education.The physical exercise was significantly more frequent in controls.The gender and age affect the assessment of physical activity performed by both groups of patients.Regarding employment status,most patients with RA were housewives (43%) whereas in controls were external employers (44%).RA patients most frequently used public transportation (39%) while controls use their cars (52%).The mean consumption of tobacco, alcohol and coffee was higher in controls but the significance level decreased in multivariate analysis,confirming the influence of gender and age on these variables.The average number of children in RA patients was higher than controls,a difference that was not confirmed by including confounding factors. Conclusions In this large comparative study we describe for the first time the general epidemiological characteristics in patients with RA and healthy subjects representative of the Spanish population.RA patients are older as compared with controls and most of them are housewives with no education or primary education.The influence of gender confirms the significance level of physical activity,alcohol consumption, smoking, coffee intake, weight, height and average number of children. Disclosure of Interest None declared

Some patients (20–30%) with spondyloarthropathies (SpA) have a persistent and disabling disease,1 for which a limited number of alternative therapeutic approaches exist.2 The successful results from randomised, double blind, placebo controlled trials in ankylosing spondylitis (AS) and SpA which have been published 3–5 suggest that treatment with infliximab is highly effective. However, in most of these studies, criteria for the selection of patients are based on active disease, but not on refractory disease (failure of response to previous drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs). Therefore, we aimed at assessing the effectiveness and safety of infliximab in patients with active and refractory SpA. The study was an open label, multicentre, 38 week prospective study in 40 patients with active and refractory SpA: 34 patients had AS, 3 had arthritis with related inflammatory bowel disease, and 3 undifferentiated SpA. Infliximab (5 mg/kg) was given at weeks 0, …

Objective. To map the locus for susceptibility to psoriasis in patients with psoriatic arthritis. Methods. Seventy-four patients with psoriatic arthritis and 95 patients with psoriasis vulgaris were included in this study. Polymorphic genes and microsatellite markers centromeric (C1―2―5) and telomeric (C1―4―4, OTF3, HCR and the corneodesmosin gene) to HLA-C were studied in an association analysis. Typing was also performed on a control population of 104 matched donors. Results. The allele Cw*0602 was associated both with psoriasis [49 vs 21%, P c < 0.0003; odds ratio (OR) = 3.6, aetiological factor (AF) = 0.72] and with psoriatic arthritis (62 vs 21%, P c < 0.000001; OR = 6.1, AF = 0.83). In psoriatic patients a susceptibility region telomeric to HLA-C that includes C1―4―4 (56 vs 22%, P c < 0.0002; OR = 4.39, AF=0.77), OTF3 (85 vs 60%, P c < 0.0002; OR = 3.7, AF = 0.73) and HCR (63 vs 26%, P c < 0.00001; OR = 3.8, AF = 0.74) was observed. In psoriatic arthritis patients the susceptibility region was delimited by HLA-C and C1―4―4 (384 allele, 56 vs 22%, P c < 0.0002; OR = 4.37, AF = 0.77). Conclusions. Comparing the susceptibility regions associated with the two diseases, an overlapping interval of 100 kb between HLA-C and OTF3, which might contain the psoriasis gene, can be defined.

The distribution of B27 alleles (B*2701-23) was characterized by PCR-SSP in ankylosing spondylitis and related spondyloarthropathies (SpA) in a sample of B27 positive patients from northern Spain. Six B27 alleles were identified: B*2705,02,03,07,08 and B*2713. B*2705 and 02 were the most common alleles in the SpA studied: ankylosing spondylitis (AS) (n = 89), reactive arthritis (ReA) (n = 11), psoriatic arthritis (PsA) (n = 29), and inflammatory bowel disease (IBD) (n = 21). B*2707 and B*2708 were found in PsA patients and B*2703 in one patient with IBD. B*2713 was identified in a healthy control family. B*2713 has not been reported to be represented in either ethnic group. Thus, this population shows higher levels of B27 diversity than other Caucasian groups.

To evaluate the relative contribution of the human leukocyte antigen (HLA)-B27 to psoriatic spondyloarthropathy (PsSpA) susceptibility and to analyze whether this antigen contributes to disease expression.This cross-sectional study included 70 patients (mean age 48 +/- 14.5 years; 44 men and 26 women). PsSpA was defined according to radiological findings (grade 2 or more sacroiliitis), and patients were classified into 3 main subtypes: isolated axial disease (n = 16), axial plus oligoarthritis (n = 29) and axial plus polyarthritis (n = 25). All patients were studied following a standard protocol that included the collection of demographic and epidemiological data, clinical history, radiographs, complementary tests, physical examination, and HLA-B27 testing (serological method). For functional evaluation, the Health Assessment Questionnaire-Specific for spondyloarthropathy (HAQ-S) was used. Patients with and without HLA-B27 antigen were compared on the basis of the data.Twenty-four patients (34%) carried the HLA-B27 antigen (RR 6.4, P.0004). Fifty-six percent of those patients with the isolated axial pattern had this antigen, compared with 24% in the poly-arthritis axial pattern and 31% of those in the oligo-arthritis axial group (P =.016). Univariate analysis demonstrated correlations between HLA-B27 and an earlier age of onset for both psoriasis (P =.028) and arthritis (P =.006), male gender (P =.002), bilateral sacroiliitis (P =.002), and uveitis (P =.026). HLA-B27 negative patients developed more peripheral erosions than HLA-B27 positive patients (P =.05). No correlation was found between B27 and clinical symptoms of back involvement, syndesmophytes, or functional impairment.The HLA-B27 antigen is not only important for PsSpA susceptibility, but also determines some clinical features. This antigen was associated with earlier age of psoriasis and arthritis onset, bilateral sacroiliitis, and male gender. However, it was not associated with either the severity or extension of the spondylitic process or with functional impairment.

To analyze the genetic contribution of HLA in development of psoriatic arthritis (PsA) and to study whether MICA is primarily associated with PsA or whether its association is secondary to linkage disequilibrium with centromeric genes, such as MICB, TNFA, or HLA-DRB1.DNA samples from 81 Spanish patients with PsA and 110 healthy controls were examined by polymerase chain reaction (PCR) sequence-specific primers to type HLA-Cw and HLA-DRB1, PCR sequence-specific oligonucleotides to determine HLA-B, and PCR restriction fragment length polymorphism for tumor necrosis factor-alpha promoter polymorphisms at positions -238 and -308. Analysis of microsatellite polymorphisms in the transmembrane region of MICA and in intron 1 of MICB was also carried out.HLA-Cw*0602 was significantly increased in PsA [60% vs 17%; p(c)0.00002, OR 7.33, etiological fraction (EF) 0.52]. MICA-A9 (60% vs 30%; p(c) = 0.0002, OR 3.57, EF 0.43) and the microsatellite MICB-CA-22 allele (23% vs 7%; p(c) = 0.028, OR 3.9, EF 0.17) were also significantly increased in PsA. MICA-A9 was in linkage disequilibrium with MICB-CA-22 (delta = 0.6). The association of MICA-A9 was independent of MICB-CA-22 and Cw*0602, since it was also associated in MICB-CA-22 negative (p(c) = 0.0015, OR 2.96, EF 0.34) and in Cw*0602 negative patients (p(c) = 0.034, OR 2.83, EF 0.34). TNFA and DRB I alleles were not significantly associated with PsA.Cw*0602 and MICA-A9 appear to be the strongest genetic susceptibility factors for PsA. However, MICA-A9 was associated independently of Cw6. HLA-B alleles and MICB-CA22 are associated secondarily to linkage with MICA. TNFA and HLA-DRB1 were not associated with PsA susceptibility, and our data suggest that their reported association may only reflect the linkage disequilibrium with MICA-A9 among the different populations studied.

Background Psoriatic Arthritis (PsA) is a complex disease and is present in ∼11% in patients with Psoriasis (Ps). Recently, Genomewide Association Studies (GWAS) have expanded the number of risk loci for Ps in >20 new loci. Two of these genes, ERAP-1 and HLA-C , have been shown to interact epistatically in the risk to develop Ps. Objectives We have studied the presence of new genetic interactions between Ps risk lci with the HLA region in Purely cutaneous Psoriasis (PsC) and PsA. Methods Within each Ps risk locus (n=31), the SNP having the highest statistical evidence was selected. The 31 SNPs were genotyped using Taqman technology in a cohort of n=955 PsA, 1,050 PsC and 1,497 hypernormal controls of the Spanish population. The presence of statistically significant gene-gene interactions was performed using a logistic regression model with three parameters to determine the presence of interaction at the allelic level. Results We replicated the previously described interaction of HLA-C and ERAP1 in the PsC cohort but not in the PsA cohort. We identified, for the first time, a significative epistatic association between HLA-C and SERPINB8 . Microarray gene expression studies on cutaneous biopsies corroborate the presence of this interaction at a functional level. In PsA, no statistically significant interactions where identified with variation at HLA-C . However, 6 of the studied genes showed a significant ( P HLA-B27 positivity. Conclusions The present study has identified new genetic interactions associated with the risk to develop PsC and PsA. The functional study of these interactions will improve our knowledge of the biological basis of these complex diseases. Disclosure of Interest None Declared

Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) loci are both highly polymorphic, and some HLA class I molecules bind and trigger cell-surface receptors specified by KIR genes. We examined whether the combination of KIR3DS1/3DL1 genes in concert with HLA-B27 genotypes is associated with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive Caucasian populations were selected, one from Spain (71 patients and 105 controls) and another from the Azores (Portugal) (55 patients and 75 controls). All were typed for HLA-B and KIR (3DS1 and 3DL1) genes. Our results show that in addition to B27, the allele 3DS1 is associated with AS compared with B27 controls (p < 0.0001 and p < 0.003 in the Spanish population and Azoreans, respectively). We also observed that the association of KIR3DS1 to AS was found in combination with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population (30.9% in AS versus 15.2% in B27 controls, p = 0.02, odds ratio (OR) = 2.49) and in Azoreans (27.2% in AS versus 8.7% in B27 controls, p = 0.01, OR = 4.4 in Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27 controls (p < 0.0001 in the Spanish population and p < 0.003 in Azoreans). The presence of this allele in combination with Bw4-I80 had a protective effect against the development of AS in the Spanish population (19.7% in AS, 35.2% in B27 controls; p = 0.03, OR = 0.45). The presence of KIR3DS1 or KIR3DL1 in combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development of AS. The susceptibility to AS could be determined by the overall balance of activating and inhibitory composite KIR-HLA genotypes.