V. Martínez Taboada

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study

Objectives To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. Methods SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patients global health component (DAS28-3)–erythrocyte sedimentation rate (ESR) over 6 months. Results 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3–ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3–ESR at 6 months was significantly greater in rituximab than TNFi patients: −1.5 (0.2) vs −1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (−1.7 vs −1.3; p=0.017) but not intolerance (−0.7 vs −0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3–ESR with rituximab than with TNFi (−1.6 (0.3) vs −1.2 (0.3); p=0.011), particularly those switching because of inefficacy (−1.9 (0.3) vs −1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. Conclusions These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

FRI0387 Factors associated with osteoporosis and fracture in patients with sjÖgren primary syndrome

Background Primary Sjögren’s syndrome (SSp) is a systemic autoimmune disease characterised by exocrine gland affectation and multisystem involvement. In addition to the systemic inflammatory affectation, patients with pSS have additional risk factors to develop osteoporosis (OP) and its major complication, osteoporotic fracture. Objectives The aim of the study is to determine the sociodemographic and clinical factors of pSS associated with the presence of OP and osteoporotic fracture in patients with pSS from the SJOGRENSER registry. Methods SJOGRENSER is a descriptive, cross-sectional and multicenter study of patients with pSS classified according to European-American consensus criteria. Patients attended in consultations of 33 Spanish rheumatology services were randomly included. Both the medical history and the medical interview were used to obtain the data. Epidemiological, clinical, serological and complications were collected. The continuous and categorical variables were analysed by means, medians and frequencies, with their respective deviations and interquartile ranges (p25-p75). Bivariate and multivariate analyses were carried out using a binomial logistic regression to study the factors associated with osteoporosis and osteoporotic fracture in pSS. Results In the SJOGRENSER registry, 437 patients were included (95% women, with a median age of 58.63 (50.02–67.98) years). The prevalence of OP in the cohort was 18.54% (81 patientes). The prevalence of OP in men (n=21) was 19%, 2 men in the age group of 51–64 years and 2 in the group of >64 years. Three hundred of the women in the registry were menopausal (76.4%); a total of 67/300 women with menopausia had OP (15%). A total of 37 osteoporotic fractures (8.5%) were recorded in the cohort. Factors associated with OP in women with SSp in the bivariate analysis were: age (60.5% in the group of >64 years, 28% in the group of 51–64 years and 2.6% in the group ≤50 years, p<0.001), the time course of the disease (11.35 (SD 7.95) vs 7.8 (SD 6.14), p<0.001), the age of menopause (47(SD 7.29) vs 48.11 (SD 5.67), p=0.020), the ESSDAI (6 (DS 7) vs 4 (DS 5), p=0.020), and presence of anti-La (77.6% vs 64.7, p=0.030). In the multivariate analysis, there was an association between OP and age in the 51–64 age group, OR 9.993 (95% CI, 2.301–43.399, p=0.002), age >64 years, OR 20.610 (CI 95% 4.679–90.774, p<0.001) and time course of the disease, OR 1.046 (95% CI 1.008–1.085, p=0.017). Similarly, an association was found between the fracture and age in the 51–64 age group, OR 5.068 (95% CI, 1.117–22.995, p=0.035), age >64 years, OR 7.674 (95% CI 1.675–35.151, p<0.009), the time course of the disease, OR 1.049 (95% CI 1.003–1–097, p<0.036) and the ESSDAI score, OR 1.080 (95% CI, 1.029–1–134, p=0.002). Conclusions Patients with pSS have a considerable prevalence of osteoporosis and osteoporotic fracture. Age and time of evolution were factors associated with the development of OP, and similarly, age, time of evolution of the disease and ESSDAI were factors associated with the development of fracture in patients with pSS. Disclosure of Interest None declared

FRI0358 Factors associated with pulmonary manifestations in sjogren syndrome

Background Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disorder characterised by lymphocytic infiltration of the exocrine glands resulting in dry syndrome. Approximately one-third of patients have extraglandular systemic findings, such as respiratory symptoms (43%–75%), that are also considered to be a cause of morbidity and conditioning quality of life. The aim of the study is to estimate the prevalence of pulmonary manifestations in pSS, and to identify factors associated with its development. Methods SJOGREN-SER (Spanish Rheumatology Society Registry of pSS) is a multicenter cross-sectional study of pSS patients under active follow-up at 33 rheumatology departments through Spain. Patients fullfilled the European-American consensus criteria of 2002. Airway disease (dry cough, xerotrachea, bronchial, hyperresponsiveness and airway obstruction) and pulmonary involvement (ILD, pulmonary amyloidosis, pulmonary arterial hypertension, vasculitis and pleural involvement) were considered according to the definition contained in EULAR Sjögren’s Disease Activity Index (ESSDAI), as well as Sjögren’s Syndrome Disease Damage Index. Bivariate logistic regression models and multivariate analysis were used to establish the independent effect of patient characteristics associated with pulmonary manifestations. The results were considered significant when the P value was less than 0.05. Results The SJOGREN-SER registry included 437 patients (95% women, median age at inclusion 59 years [50–68 years] and mean of ESSDAI 2 (IQR 0–4)). One hundred and seventeen patients (26.8%) had pulmonary manifestations (19.2% airway disease and 9.8% pulmonary involvement). Ten patients presented both. Sociodemographic characteristics were: mean age 59.5 years (SD: 11.46), 94.9% women and 19.6% smokers or former smokers. Patients with pulmonary manifestations had higher ESSDAI score (6 (SD 6) vs 4 (SD 5)), prolonged disease duration (10.05 years (SD: 7.15) vs 7.7 (SD 6.3)) and were ANA positive more frequently (94.9% vs 62.2%). Airway involvement preceded or occurred at the time of diagnosis in 46.4% of patients. Pulmonary involvement occurred 5 years after the diagnosis of pSS in 37.2% of them. [RS1] Twenty-nine patients (6.6%) were diagnosed with ILD. The most frequent radiological patterns were: Non-Specific Interstitial Pneumonia n=14, Usual Interstitial Pneumonia n=5, Lymphocytic Interstitial Pneumonia n=5 and Cryptogenic Organised Pneumonia n=2. Stepwise multivariate analysis was performed including the following variables: sex, age, laboratory findings, disease duration, smoking and ESSDAI. Disease duration (OR of 1.05 (95% CI, 1.006–1.083)), ESSDAI score (OR of 1.044 (95% CI, 1.006–1.083)) and positivity for ANA (OR of 3.725 (95% CI, 1.141–12.159)) were found to be associated factors with pulmonary involvement in pSS. Conclusions Prevalence of pulmonary manifestations in this cohort of pSS patients is substantial due to both airway disease and pulmonary involvement. Disease duration, activity of pSS according to ESSDAI score and ANA positivity were factors associated with the development of pulmonary manifestation. Disclosure of Interest None declared

AB0524 How do we treat dryness in patients with primary sjÖgren’s syndrome? a nationwide study in spain from the sjogrenser registry

Background Primary Sjögren syndrome (pSS) is a systemic autoimmune disease whose main characteristic is the involvement of the exocrine glandular system. Thus, its most common clinical manifestation is eye and mouth dryness. No therapy has been demonstrated to significantly modify disease course and, currently, evidence-based therapy for pSS is mainly limited to symptomatic drugs for drynes. Objectives To describe the dryness treatment in a cohort of primary Sjögren Syndrome patients. Methods SJOGRENSER registry is a multicentre descriptive cross-sectional study of pSS patients, fulfilling European/American criteria, from 33 Spanish rheumatology departments. Data were collected by reviewing clinical records and interviewing the patients. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistics using means, medians and ranges. Chi square test was used to compare categorical variables. A p<0.05 was considered significant. Results Four hundred and thirty seven patients were included (female 95%; median age 58 years). Ninety four per cent of the patients complained of daily, persistent, troublesome dry eyes for more than 3 months, 92% had sensation of sand in the eyes, 16% developed corneal ulcer. Ninety four per cent of the patients complained of dry mouth for more than 3 months and 27% had dental loss. The most frequent ocular dryness treatments were tear substitutes (96%), followed by lubricating ophthalmological ointments (46%), autologous sera solutions (14%), topical corticosteroids (13%), topical cyclosporine (6%). Comparing patients with and without ocular dryness, only pilocarpine and lubricating eye ointment were used significantly with more frequency in symptomatic patients (p<0.05); tear substitutes was used significantly with more frequency in symptomatic patients only in the subgroup of patients that used tear substitutes more than 3 times a day. The most frequent oral dryness treatments were chewing gums or candies without sugar (65%), followed by pilocarpine (56%), special toothpaste (22%), mucolytic agents (20%), saliva substitutes (19%), lubricating oral gel (13%) xylitol (11%) and fluoride (11%). Comparing patients with and without oral dryness, chewing gums or candies without sugar, xylitol and fluoride were not used significantly more frequently in symptomatic patients. In contrast, saliva substitutes, lubricating oral gel, pilocarpine, mucolytic agents and specific toothpaste were used significantly more frequently in symptomatic patients (p<0.05). The median in ESSPRI (Eular Sjögren’s Syndrome Patient Reported Index) in SJOGRENSER cohort was 5.3 (p25-p75, 3.67–7). Only topical corticosteroids and pilocarpina were used significantly more frequently in patients with a dryness VAS≥5 in ESSPRI index. Conclusions Despite the high number of symptomatic patients, the use of dryness treatments is limited in pSS patients. Chewing gums or candies without sugar, xylitol and fluoride remain underutilised in this cohort. Despite the dryness VAS score, patients do not seem to use all the symptomatic therapeutic options available. Disclosure of Interest None declared

AB0519 Laboratory abnormalities in patients with primary sjogren's syndrome

Background Primary Sjögrens syndrome (pSS) is a chronic systemic autoimmune disease often accompanied by analytical abnormalities. Altered levels in serum protein concentration, blood cell count and autoantibodies contribute to the broad spectrum of biological manifestations that characterize pSS. Objectives The objective of this study is to evaluate the presence of laboratory abnormalities in patients with pSS from the SjogrenSER registry. Methods We conducted a multicentre transversal study of a cohort of pSS patients fulfilling 2002 European/American criteria, from 33 Spanish rheumatology departments. Every patient was interviewed for data collection and signed an informed consent. Data were also collected by reviewing medical records. Local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians and rates. Chi-square was used to establish the statistical associations. A p<0.05 was considered significant. Results Four hundred and thirty-seven patients were included. Ninety-five percent of them were women. The median age of the cohort was 58 years. AntiRo antibodies were present in 93.6% of patients and AntiLa antibodies in 67.3% of patients. All patients were ANA+. Rheumatoid factor (RF) was positive in 64.8% of patients. Low levels of C3 and C4 were observed in 14.87% and 14.19% of patients, respectively. Polyclonal hypergammaglobulinemia (HGG) was present in 53% of patients. Thirteen patients had cryoglobulins (2.97%). An increase in β2microglobulin was observed in 22.2% of patients. Fifty-six percent of the patients had hematological involvement: 29% of the patients had anemia, 38% had leukopenia (38% lymphopenia, 10.5% had neutropenia), and 9% had thrombocytopenia. The median ESR was 25 mm. Age at diagnosis and age at onset of symptoms were significantly lower in patients presenting RF+ vs RF- (48.71 vs 53.73, p<0.001 and 44.76 vs 49.53, p=0.001, respectively), decreased C3 vs normal C3 (45.66 vs 51.18, p=0.004 and 42.2 vs 46.99, p=0.018, respectively), decreased C4 vs normal C4 (47.02 vs. 50.89, P=0.042, for age at diagnosis) and HGG (47.59 vs 54, p<0.001, and 43.44 vs 50.16, p<0.001, respectively). ESR was significantly higher in patients with hematological involvement (35.94 vs 26.24, p<0.001), RF+ (36.39 vs 22.91, p<0.001), decreased C3 (37.8 vs 30.53, p=0.026) and C4 (38.71 vs. 30.42, p=0.04)), HGG (36.21 vs 26.03, p<0.001) and increased β2microglobulin (38.80 vs 29.71, p=0.009). ESSDAI (Eular Sjögren Syndrome Disease Activity Index) was significantly higher in patients with haematological involvement (5.58 vs 3.69, p<0.001), RF+ (5.40 vs 3.53, p<0.001) and HGG (5.31 vs 3.93, P=0.011). The median ESSDAI score was 2 (P25-P75, 0–4). Conclusions in SjogrenSER registry all patients were serologically positive. More than half of the patients presented abnormalities in serum proteins and 14% had hipocomplementemia. More than half of the patients had abnormalities, mostly leucopenia and lymphopenia. Patients with analytical alterations were younger at the time of diagnosis and had more often elevated ESR and higher ESSDAI score. Disclosure of Interest None declared

OP0233 Genome-Wide Pathway Analysis Reveals that VEGF Genetic Pathway Is Associated with Oral Ulcers in Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease with heterogeneous clinical manifestations. Recent studies have suggested the existence of a genetic basis for the diverse SLE clinical phenotypes. Also, there is increasing evidence indicating that a substantial part of the genetic variation associated with complex diseases is explained by small-effect genes from common genetic pathways. Objectives The objective of the present study was to identify new genetic variation associated with SLE phenotypes using a genome-wide association study at the pathway level. Methods A total of 598,258 SNPs were genotyped in a discovery cohort of n=482 SLE patients of southern European ancestry using the Illumina platform Quad610. After quality control analysis, including ancestry estimation using principal-component analysis, genome-wide pathway analysis was performed. A total of 14 clinically relevant SLE phenotypes were tested for association with n>700 reference genetic pathways. Significantly associated pathways (corrected P-value <0.05) were subsequently tested for validation in an independent cohort of n=425 SLE patients from the same ancestry. Both discovery and validation cohort patients were Caucasian European and from Spanish origin, and were recruited by rheumatology departments from n=15 Spanish university hospitals. The validated genetic pathways were functionally characterized using in silico analysis on cell types of relevance in SLE pathogenesis. Results In the discovery stage, two genetic pathways were significantly associated with the presence of oral ulcers and antinuclear antibodies in SLE (PFDR<0.05). In the replication stage, we validated the association between oral ulcers and vascular endothelial growth factor (VEGF) genetic pathway (P=1.3e-2). Analyzing the transcriptional effect of the topical immunotherapies used for the treatment of oral ulcers in SLE, we found a significant differential expression of VEGF pathway genes (P<0.05). Conclusions In this work we have performed the first genome-wide association study for clinically relevant SLE phenotype using a pathway-based approach. With this new approach, we have identified and validated the association of VEGF genetic pathway with oral ulcers in SLE. These findings represent an important step towards the characterization of the genetic basis of phenotype heterogeneity in SLE. Disclosure of Interest None declared

FRI0325 Clinical and Serological Features According To Age at Diagnosis of Primary Sjögren's Syndrome

Background Primary Sjögrens syndrome (pSS) is a chronic systemic autoimmune disease that usually affects middle age women. It is characterized mainly by the involvement of the exocrine glands; However, patients with pSS presents a broad spectrum of systemic involvement and serologic characteristics. Objectives The aim of this study is to analyze clinical and serological differences in different age at diagnosis groups in a pSS Spanish cohort. Methods This is a multicenter transversal study of pSS patients whose fulfilled European-American consensus criteria from thirty-three Rheumatology Units. The patients were randomized into the following age groups: <35 years, 35–50 years, 50–65 years and>65 years. Epidemiological, clinical and serological data were collected. All patients signed an informed consent, and the study was approved by the local ethics committees. Qualitative data were compared using the Chi-square tests. Quantitative variables were analyzed with a Kruskal-Wallis test. A value of p<0.05 was considered as significant. Results Four hundred and thirty-seven patients were included. The median age of the cohort was 58 years. Ninety-five percent of them were women.There were no statistically significant differences in the men and women percentage.The disease symptoms were initiated more frequently in 35–50 years group (38.5%).There were no statistically significant differences in the time to disease progression in the four age at diagnosis groups. No statistically significant differences were found in sicca syndrome among age groups. Ocular and oral symptoms were present in 95% of patients. The glandular involvement (46.7%), central nervous system (14.13%) and Raynauds phenomenon (29.3%) showed significantly more often in patients under 35 years. Genital involvement (54.5%) and asthenia (72.4%) showed significantly more often in the group of 35–50 years. The gastrointestinal involvement (20%) occurred significantly more frequently in the group of 50–65 years. Splenomegaly and cardiac involvement were less frequent manifestations in all four groups of patients (<4%). Rheumatoid factor (RF) positive was significantly higher in those under 35 years (77.1%). The anti-anti-SSA and SSB antibodies tended to be more frequently positive in groups <35 years (96.7% and 79.3% respectively) and>65 years (100% and 75% respectively). There were no significant differences in the ANA, anti-DNA, anti-Sm, anti-RNP, cryoglobulins and antiphospholipid antibodies values between groups. Conclusions Patients under 65 years old have an increased degree of systemic involvement. There are no differences in the presence of sicca syndrome. The FR is significantly more common in patients younger than 35-year-old, while the anti-Ro and anti-La antibodies tend to be it in more extreme age groups. Disclosure of Interest None declared

AB0413 Systemic Therapy in Primary Sjögren Syndrome Patients

Background Primary Sjögren syndrome (pSS) is a systemic autoimmune disease involving mainly the exocrine glandular system. Nevertheless, its clinical spectrum includes the development of multiple extra-glandular manifestations which will be determinant for the use of systemic therapy. Objectives The aim of our study was to describe the systemic therapy in a pSS cohort assisted in Spanish Rheumatology Departments and its association with the involvement of different organs. Methods This is a multicenter descriptive transversal study of pSS patients fulfilling European/American consensus criteria. Patients were included by randomization from thirty-three Rheumatology departments. Data were collected by reviewing clinical records and interviewing the patients. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates. Chi-square was used to establish the statistical associations, being considered a p<0,05 as significant. Results Four hundred and thirty-seven patients were included. Ninety-five percent of them were women. The median age of the cohort was 58 years. Eighty-four percent of the patients have been treated (currently or previously) with non-steroidal anti-inflammatory drugs (NSAID), 49% had been treated with glucocorticoids (GC), 7% with boluses of GC, 51% with antimalarial, 13% with methotrexate (MTX), 10% with azathioprine (AZA), 4% with mycophenolate mofetil (MM) and 3% with cyclophosphamide (CF). NSAIDs were significantly used more frequently in patients with joint involvement. GC were significantly used more frequently in patients with joint, pulmonary, central and peripheral nervous system (CNS and PNS) involvement and cytopenia. GC boluses were used significantly more frequently in patients with musculoskeletal, pulmonary and nervous system involvement. Antimalarials were significantly used more frequently in patients with joint involvement. MTX was significantly used more frequently in patients with joint, CNS involvement and cytopenia. AZA was significantly used more frequently in patients with lung and CNS involvement and cytopenia. MM was significantly used more frequently in patients with renal, lung and PNS involvement, and cytopenia. CF was significantly used more frequently in patients with joint, pulmonary, CNS and PNS involvement. Conclusions Despite the absence of clinical controlled studies demonstrating efficacy and safety, systemic therapy use in SSp patients is very frequent. Its use is mainly associated with the presence of musculoskeletal, neurological, pulmonary and haematological manifestations. Disclosure of Interest None declared

SAT0591 Consensus Statement for The Evaluation and Management of Patients with Autoimmune and Inflammatory Diseases during Fertility, Pregnancy, Post-Partum and Breastfeeding

Background Nowadays there is a great variability in evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding, in part due to lack of knowledge. Objectives To develop recommendations on the evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding based on the best evidence and experience. Methods Recommendations were generated following nominal group methodology and Delphi technique. A panel of experts was established (12 rheumatologists). A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in the 1st panel meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinements. A national survey analyzing different aspects of this topic was undertaken separately. Then, a Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Results A total of 14 recommendations (see figure) were generated on the pre-conception period (oral and hormonal anticonception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High risk situations were included as lupus or antiphospholipid syndrome. A consensus >90% was reached in all but one recommendation. Conclusions These recommendations are intended to provide rheumatologists, patients, families and other stakeholders a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding. Disclosure of Interest None declared

THU0010 Genome-Wide Association Study of Anti-Cyclic Citrullinated Protein-Positive Rheumatoid Arthritis Identifies a New Risk Locus in SLC8A3

Background There is strong evidence that Rheumatoid Arthritis (RA) patients expressing anti-cyclic citrullinated peptide antibodies (ACPA) have a differential genetic background compared to ACPA-negative RA patients. Objectives We performed a genome-wide association study (GWAS) on ACPA-positive RA patients to identify additional disease susceptibility genes. Methods A total of 924 ACPA-positive RA patients and 1,524 healthy controls were genotyped in 582,591 single-nucleotide polymorphisms (SNPs) in the discovery phase. The most significant SNPs were then analyzed in an independent cohort of 863 ACPA-positive patients and 1,152 healthy controls. Results In the discovery phase we found suggestive association (P <5e-4) for 60 novel loci with the risk to develop ACPA-positive RA. In the validation phase, we nominally replicated the association of 12 candidate loci (P<0.05 same direction of effect as in GWAS). Combining the data from the discovery and validation cohorts we found a genome-wide significant association between an intronic SNP in Solute Carrier family 8 gene (SLC8A3) and the risk to develop ACPA-positive RA (OR (95%CI): 1.42 (1.25-1.6), combined P=3.19e-8). Conclusions This study identified a new locus associated with ACPA-positive RA. These results support the evidence that RA patients positive for ACPA have a specific genetic background. Disclosure of Interest None declared