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Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the “real-life” results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1–1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3–6.1), being constant over time (0–5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% CI 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = 0.0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-a agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Background: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. Objective: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. Methods: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. Results: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of = 5). Limitations: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. Conclusion: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Background: Methyldibromo glutaronitrile (MDBGN) was one of the most frequent and relevant allergens found in patch testing at the beginning of this century. In 2008, this preservative was banned from cosmetics in Europe and ever since the prevalence of contact allergy to MDBGN has progressively decreased. Despite that gradual decline, MDBGN is still patch-tested in most baseline series. This study assessed the frequency of MDBGN sensitization, epidemiological characteristics of allergic patients, and the relevance of positive patch tests in a nationwide Spanish registry (REIDAC). Patients and methods: We evaluated consecutively patch-tested patients in all participating centres. Using these data, we calculated the proportion of patients with positive patch tests to MDBGN from June 2018 to June 2020 and evaluated the relevance of the positive patch tests. Results: One hundred and fourteen out of 5072 (2.24 %) tested patients were sensitized to MDBGN. Clinical current relevance was confirmed in only one case. Conclusion: Although the frequency of contact allergy to MDBGN remains high, no clinical significance was found in most of these patients (5072 tests needed to obtain one relevant positive result). The clinical usefulness of this allergen seems weak and its continued inclusion in the European baseline series is questionable. Highlights: In 2008 methyldibromo glutaronitrile (MDBGN) was banned from cosmetics in Europe and since then, the prevalence of allergy to it has progressively decreased. Nevertheless, it is still being tested in European baseline series. This study assessed the frequency of MDBGN sensitization, epidemiological characteristics of allergic patients as well as the relevance of positive patch tests in a nationwide registry (REIDAC). The frequency of allergy to MDBGN remains high, but no clinical significance was found. Most of these patients are aged >40 years and probably represent historical sensitizations.

BACKGROUND The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Introduction and objectives Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. Material and method We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. Results The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. Conclusions No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis.

Background Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. Objectives To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. Methods Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. Results A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. Conclusions Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.

Background Little is known about the adverse events (AEs) that lead to suspension of systemic treatments of psoriasis in clinical practice. Objective The study aimed to investigate to AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm). Materials and methods Multicenter, prospective, cohort study of patients with moderate-to-severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies. Results A total of 4218 courses of treatment were used in 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient-years (PY) (95%CI:12.14-13.93), 9.34 events/100PY (95% CI:8.44-10.33) for biologics and 19.67 (95%CI:17.9-21.6) events/100PY for classics (p< 0.001). Of 810 discontinuation-related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100PY (95%CI:41.91-57.72)] and infliximab [26.52/100PY (95%CI:20.98-33.51). Ustekinumab presented the lowest IR (2.6/100PY (95%CI:1.83-3.69). Limitations Observational study with potential selection bias. Conclusion Biologic therapies are associated with a lower rate of discontinuation-related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence. This article is protected by copyright. All rights reserved.

Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries.We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs.Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016.While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Background: The management of HIV-positive patients with psoriasis is controversial and limited to individual cases or short series of patients. Objectives: To evaluate the safety and effectiveness of conventional and biologic immunosuppressive drugs in the treatment of patients with psoriasis and concomitant HIV infection. Methods: A retrospective multicenter study was conducted. The study included data from 2008 to 2016. Inclusion criteria were: HIV adult patients with moderate-to-severe psoriasis, HIV viral load determinations at baseline and at least after 6 months of treatment, and systemic immunosuppressive treatment for at least 6 months. A descriptive analysis was performed. Results: Twenty-three patients with plaque-type psoriasis and HIV infection (five with AIDS) were included. Median follow-up time was 3.2 years. The main drugs used were etanercept, methotrexate, and ustekinumab. In most cases, viral load and CD4 cell count not only remained stable but also improved throughout the follow-up. Six patients presented severe adverse events during the follow-up, four of them in the AIDS stage. At the end of the follow-up period, 76.5% of the patients had achieved a PASI 75. Conclusion: Biologic drugs, both anti-TNF alpha agents and ustekinumab, seem to have an acceptable safety profile and high effectiveness in HIV-positive patients.

Data on infections in patients exposed to biologic therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other immune-mediated connective tissue diseases (ICTD). The purpose of this study was to describe and to compare the risk of serious infections (SI) in patients with RA and other ICTD on anti-TNF or rituximab and to identify predictors of SI. We analyzed RA or other ICTD patients on anti-TNF or rituximab included in the Spanish registry BIOBADASER 2.0 (2000-2011). For each disease group, incidence rate (IR), mortality rate (MR) and IR ratio (IRR) of SI with 95% CI were estimated. Risks were then standardized by age and sex to the general population. Risk factors for SI were assessed by Poisson regression models. A total of 3,301 patients on anti-TNF (n = 3,166) or rituximab (n = 135), of which 176 (5%) had ICTD other than RA, were analyzed. IR of SI was higher in non-RA ICTD than in RA, with an IRR of 3.15 (95% CI 1.86, 5.31) before adjustment and 1.96 (95% CI 1.06, 3.65) after adjustment for age, comorbidity and corticoid use. Mortality due to infections was higher in ICTD although it did not reach statistical significance. Age, disease duration, comorbidities, corticosteroids and ICTD different to RA were all independently associated with SI. Patients with ICTD other than RA are at a high risk of SI when prescribed anti-TNF or rituximab, partly due to the excess comorbidity and immunosuppressive co-treatment, but also to the inflammatory disease. When evaluating the risk/benefit ratio of off-label medications in ICTD patients, age, comorbidities and corticoid use should carefully be taken into account, applying adequate preventive measures.

Objective. To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. Methods. We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biologicos de la Sociedad Espanola de Reumatologia) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. Results. A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. Conclusion. The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases. Copyright © 2013 by the American College of Rheumatology.

OBJECTIVE The objective of this study was to analyse the performance of the Assessment of SpondyloArthritis International Society (ASAS) criteria for the classification of SpA in early SpA clinics. METHODS We used a cross-sectional study of patients referred to early SpA units within the ESPERANZA programme (a Spanish nationwide health management programme designed to provide excellence in diagnosis and care for early SpA). Patients were eligible if they were

Objectives To evaluate the validity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) in early spondyloarthritis (SpA) in comparison with conventional clinical measures of disease activity. Methods Six hundred and seventy-six incident cases of early SpA from the Esperanza programme were included. Patients were categorised into high and low disease activity states based on patient and physician global assessment scores and on the physician9s decision to start treatment with a disease-modifying antirheumatic drug or tumour necrosis factor blocker. The discriminant ability of ASDAS-C-reactive protein (CRP) and ASDAS-erythrocyte sedimentation rate (ESR) was tested using standardised mean differences between patients with high and low disease activity. Convergent validity was tested by Pearson correlation between ASDAS versions and other measures of disease activity. Results ASDAS-ESR and ASDAS-CRP showed good correlation with BASDAI (r=0.79 and 0.74, respectively). Both indices correlated well with the patient global assessment (r=0.70 in both indices) and moderately with the physician global score (r=0.46 and 0.47, respectively). CRP and ESR showed poor correlation with patient- and physician-derived measures. ASDAS performed similarly across the global SpA sample, ankylosing spondylitis (AS), non-radiographic axial SpA and peripheral SpA. Conclusions ASDAS performed as a valid activity score even being slightly better than the Bath Ankylosing Spondylitis Disease Activity Index in its ability to discriminate between high and low disease activity in early SpA. ASDAS performed similarly in AS, early forms of SpA, non-radiographic axial SpA and peripheral SpA.

Background and objective: We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. Methods: Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. Results: Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. Conclusion: Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size. (C) 2016 AEDV. Published by Elsevier Espana, S.L.U. All rights reserved.

Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person-years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1-2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24).

Objective To describe the main demographic and clinical features of patients with spondyloarthropaties in Spain. Patients and methods Review of randomized clinical charts of patients with spondyloarthropaties with at least one visit to the rheumatologist in the previous two years. Information was collected on demographic and clinical data (duration of illness, diagnostic category, disease activity, extra-articular manifestations, comorbidity and work disability). Results 1168 patients were included in the study. Their median age was 49.2 years (39.7–60.5), 68.0% were males, and median time of disease was 105.1 months (48.4–192.5). The diagnoses and clinical data such as the BASDAI were reported only in 34.0% of the patients. The most widely used measure of metrology, the Schober test, was missing in 37.7% of the clinical charts. The patients included had the following diagnoses: ankylosing spondylitis (n=629, 55.2%), psoriatic arthritis (n=253, 22.2%), undifferentiated spondyloarthritis (n=184, 16.1%), arthritis associated to inflammatory bowel disease (n=50, 4.4%), and reactive arthritis (n=16, 1.4%). The most common extra-articular manifestations were psoriasis (20.8%), anterior uveitis (19.4%), and enthesitis (16.9%). Some kind of work disability was reported in 8.3% of the patients. Conclusions Demographic and clinical characteristics of patients with spondyloarthropaties in Spain do not differ as a whole from other published studies, except for undifferentiated spondyloarthritis, which was more likely in our patients than in other studies. The quality of the records of activity in the clinical charts could be improved.

Objective: To identify characteristics of early arthritis units, that may be associated with better referral eficiency. Methods: A national survey of the 36 early arthritis units (EAU) in Spanish Rheumatology Units in 2004 (SERAP project). Survey collected information about general practitioners (GP) educational program to improve knowledge and practical skills of early arthritis, networking and feed-back system and referral efficiency. EAU were classified in two groups according to 25 and 50% of inappropriate referral process, respectively.

Objective To identify characteristics of early arthritis units, that may be associated with better referral eficiency. Methods A national survey of the 36 early arthritis units (EAU) in Spanish Rheumatology Units in 2004 (SERAP project). Survey collected information about general practitioners (GP) educational program to improve knowledge and practical skills of early arthritis, networking and feed-back system and referral efficiency. EAU were classified in two groups according to 25% and 50% of inappropriate referral process, respectively. Results Thirty four of the 36 (94%) EAU, answered the survey. GP were trained in only 1 medical meeting in the primary care clinic, with one or more rheumatologists responsible of GP education. Fourteen of the 34 EAU (42.4%) regularly interacted with GP and only 20 (39.4%) contacted the GP who were responsible for the wrong referral process. Median lag time for referral to the Rheumatology out-patient clinic, was 73 days (15-365 days). The percentage of wrongly referred patients was between 0 and 80% (38%±21). Only 10 EAU (27.8%) referred patients appropriately according to the strictest criteria (25% of inappropriate referral) and 27 EAU (75%), according to 50% of inappropriate referral criteria. Conclusions Only two aspects of the EAU implementation strategy were associated with better referral efficiency: 1) interaction with the GP responsible of the inappropriate referral process and 2) a lower median lag time for referral to the Rheumatology out-patient clinic.

Objective To update the information on long-term safety of biological therapies used for the treatment of rheumatic diseases. Methods BIOBADASER is a safety registry of biological therapies established by the Spanish Society of Rheumatology. A description of BIOBADASER 2.0, a cohort composed of 14 centres within BIOBADASER, is reported from 2000 until 2009. Results The 14 centres have registered 5,493 patients, who have received 8,081 cycles of treatment with biological therapies. 30% (1,666) has received treatment with more than one biologic agent during follow-up. There have been 3,784 treatment discontinuations, with inefficacy or loss of efficacy being the most frequent cause (1,453; 38%), followed by adverse events (1,297; 34%). Up to 7,289 adverse events (AE) have been reported, of which 80% (5,764) were considered as non-serious, nearly 19% (1,340) were notified as serious and about 2% (110) were fatal. The most frequent AE were infections (2,668; 37%), followed by general problems and administration related events (10%). Cardiovascular events and cancer amounted to 7% of the total AE. Conclusions There does not seem to be a trend regarding different risks in BIOBADASER 2.0 with respect to the general registry, or to previous years.

Objective To estimate the frequency of administration related reactions (ARR), the risk window from the starting date, and finally if there are any differences between infliximab, etanercept, and adalimumab. Patients and method BIOBADASER is an adverse event registry established in 2001 for active long-term follow-up of safety of biological therapies in rheumatic patients. Data from patients, diagnosis, treatment, and adverse events are recorded. Results Four-hundred ninety-six relevant ARR were registered, 19.6% (496/2531) of all the adverse events communicated and 6.3% (496/2531) of all the patients registered. The incidence rate per 1000 patients-year with infliximab is 28 cases (95% CI, 25-31), with etanercept 0.2 (95% CI, 0.1-0.4), and with adalimumab 0.2 (95% CI, 0.07-0.7). Treatment was interrupted in more than 50% of all the ARR and 5% of all patients were hospitalized. More than 20% ARR happened after 15 months of treatment; in addition 2 appeared after 5 years of treatment. In delayed reactions the symptoms that most frequently were recorded were rash, fever, malaise, and myalgia. Conclusions ARR can appear in any moment of the treatment; they are among the most frequent causes of treatment interruption. Although with less frequency, ARR are also associated with etanercept and adalimumab with symptoms that cannot be identified as such.

Objective To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biologicos de la Sociedad Espanola de Reumatologia) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). Methods Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresion Clinica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. Results Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103–285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60–64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. Conclusion New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

Objective BIOBADASER is a prospective registry of rheumatic patients treated with biological therapies, which aim is the analysis of long-term survival and safety of these agents. Patients and methods As of January 26th 2006, 6969 patients from 100 centers were included in BIOBADASER. In total, 8321 treatments with biological therapies have been registered. Results Treatment was discontinued in 2351 (28%) occasions, mostly as a result of an adverse event (960; 41%) or inefficacy (942; 40%). A total of 2503 adverse events were notified. Of these, the most frequent ones were infections (909; 36%), followed by post-infusion reactions (500; 20%), skin lesions (255; 10%) and cardiovascular events (165; 7%). Conclusions The analysis reassures us in the increased rate of infections with biological therapies. Neither the rates of neoplasm nor of cardiac failure are significantly increased with these therapies. Specific measures have proved useful in preventing the occurrence of defined events.

Background The safety profile of biologic drugs might have substantial regional differences. Since 2009, the Brazilian Society of Rheumatology runs BiobadaBrasil, a registry for monitoring of biologic therapies in rheumatic diseases, in collaboration with other Latin America countries (BiobadaAmerica) and with Biobadaser Objectives To report the incidence of serious adverse events (SAE) in Rheumatoid Arthritis (RA) patients exposed to biologic drugs in Brazil Methods BiobadaBrasil counts on thirty two centers, from almost all Brazilian states, that prospectively include patients with active rheumatic diseases who started a biologic drug or a synthetic DMARD as a parallel control group. A constant three level monitory of data quality is maintained (online, by phone and “in situ”). This study focuses on SAE (for definition: Protocolo 1.1 at https://biobadaser.ser.es/biobadamerica/Brasil/cgi-bin/upload/documentacion.aspx) in RA patients exposed to biologics from January 2009 to June 2015. Time of exposure was set from start of the drug to the date of last administration or censorship. Continuous variables were expressed as mean with standard deviation (SD). SAE incidence rate was calculated per 1000 patient/years with 95%CI Results Out of a total of 1649 subjects with RA, 1121 were exposed to biologics (4735 p/y), 91% a-TNFs, follow-up 2.8 (2.2) yrs, 85% females, at baseline: age 50 (14) yrs, disease duration 9 (8) yrs, DAS28 5.4 (1.4). Controls were 528 (1971 p/y), follow-up 3.6 (2.2) yrs, 86% females, at baseline: age 54 (13) yrs, disease duration 6 (8) yrs, DAS28 5.1 (3.1). The incidence rates of SAE in the biologics and control groups were 86 [78, 94] vs 34 [27, 44] (ratio 2.5 [1.9, 3.3], p Conclusions In the BiobadaBrasil registry the incidence of SAE is 2 fold higher with biologics than with synthetic DMARDs, and higher with subsequent a-TNF than with the first Acknowledgement for data monitoring P Cabral, for contributing to BiobadaBrasil registry, L.Barbosa, W.Chahade, A.Hayata, A.Kakehasi, M.Pinheiro, A.Ranzolin, M.Scheinberg, F.Sztajnbok, I.Silveira Disclosure of Interest None declared

Background The safety profile of biologic drugs might have substantial regional differences. Since 2009, the Brazilian Society of Rheumatology runs BiobadaBrasil, a registry for monitoring of biologic therapies in rheumatic diseases, in collaboration with other Latin America countries (BiobadaAmerica) and with Biobadaser Objectives To report the incidence of serious infectious adverse events (SIAE) in Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) patients exposed to biologic a-TNF drugs in Brazil Methods BiobadaBrasil counts on thirty two centers, from almost all Brazilian states, that prospectively include patients with active rheumatic diseases who started a biologic drug or a synthetic DMARD as a parallel control group. A constant three level monitory of data quality is maintained (online, by phone and “in situ”). This study focuses on SIAE (for definition: Protocolo 1.1 at https://biobadaser.ser.es/biobadamerica/Brasil/cgi-bin/upload/documentacion.aspx) in RA and SpA (Ankylosing Spondylitis+Psoriatic Arthritis) patients exposed to a-TNFs from January 2009 to June 2015. Time of exposure was set from start of the drug to the date of last administration or censorship. Continuous variables were expressed as mean with standard deviation (SD). SAE incidence rate was calculated per 1000 patient/years with 95%CI Results 1601 subjects with RA (1024) and SpA (577) exposed to a-TNF drugs were included in BiobadaBrasil, 6298 p/y, follow-up 2.9 (2.3) yrs, 65% females, at baseline: age 52 (12.5) yrs, disease duration 8.6 (8) yrs. Controls were 572 (RA 528, SpA 44), 2093 p/y, follow-up 3.6 (2.2) yrs, 90% females, at baseline: age 55 (13) yrs, disease duration 5.3 (7.3) yrs. The incidence rates of SIAE were: a-TNF RA & SpA 35 [30,40] vs controls 15 [10,21], ratio 2.34 [1.6,3.5] p Conclusions In BiobadaBrasil registry, patients exposed to a-TNF drugs had an incidence rate of serious infections 2-fold that of the control group, significantly lower in SpA than in RA. Acknowledgement for data monitoring P Cabral, for contributing to BiobadaBrasil registry, L.Barbosa, W.Chahade, A.Hayata, A.Kakehasi, M.Pinheiro, A.Ranzolin, M.Scheinberg, F.Sztajnbok, I.Silveira Disclosure of Interest None declared

a b s t r a c t Objective: Our objective was to describe the variability in the management of spondyloarthritis (SA) in Spain in terms of healthcare resources and their use. Methods: A review of 1168 medical files of patients seen in randomly selected Spanish hospital rheu- matology departments. We analyzed demographic variables and variables related to the consumption of health resources. Results: The total number of visits to rheumatology were 5,908 with a rate of 254 visits/100 patient- years. The total number of visits to rheumatology specialty nurses was 775, with a rate of 39 visits/ 100 patient-years, and there were 446 hospitalizations, representing a rate of 22 per 100 patient-years. The number of admissions due to SA was 89, with a rate of 18 admissions/100 patient-years. Total visits to other specialists was 4,307 with a rate of 200/100 patient-years. The total number of orthopedic surgeries was 41, which leads to a rate of 1.8 surgeries/100 patient-years.

Objective To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. Methods We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. Results A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of −0.24 (95% confidence interval [95% CI] −0.39, −0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of −0.05 (95% CI −0.09, −0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. Conclusion Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup.

ObjectiveTo investigate in rheumatoid arthritis (RA) the rate and reason of discontinuation of tumour necrosis factor (TNF) antagonists over the past decade.MethodsRA patients in BIOBADASER 2.0 were stratified according to the start date of their first TNF antagonist into 2000–3, 2004–6 and 2007–9 interval years. Cumulative incidence function of discontinuation for inefficacy or toxicity was estimated with the alternative reason as competing risk. Competing risks regression models were used to measure the association of study groups with covariates and reasons for discontinuation. Association is expressed as subhazard ratios (SHR).Results2907 RA patients were included in the study. Competing risk regression for inefficacy shows larger SHR for patients starting treatment in 2004–6 (SHR 2.57; 95% CI 1.55 to 4.25) and 2007–9 (SHR 3.4; 95% CI 2.08 to 5.55) than for those starting in 2000–3, after adjusting for TNF antagonists, clinical activity and concomitant treatment. Competing risk regression analysis for adverse events revealed no differences across the three time intervals.ConclusionsIn RA, the discontinuation rate of TNF antagonists in the first year of treatment is higher more recently than a decade ago, inefficacy being the main reason for the increased rate. The rate of discontinuation for adverse events has remained stable.

Objectives. To assess the retention rate of TNF antagonists in elderly patients suffering from chronic arthropathies and to identify predictive variables of discontinuation by inefficacy or by adverse events (AEs). Methods. All patients treated with TNF antagonists in BIOBADASER 2.0, with a diagnosis of either RA or spondyloarthritis (SpA: AS and PsA) were included and classified as

BACKGROUND: In Europe most dogs with clinical leishmaniosis are treated with leishmanicides, typically antimonials combined with allopurinol and good clinical recovery is observed in a high number of these dogs. Through xenodiagnosis, the capacity of a treated animal to infect the vector of the disease under treatment is assessed as a measure of the chemotherapeutic efficacy of the drug used. The objective of the present study was to evaluate through direct xenodiagnosis the infectivity to Phlebotomus perniciosus of dogs naturally parasitized with Leishmania infantum after treatment, and to follow the clinical and parasite course of disease. Thirty two dogs with clinical leishmaniosis were assigned to one of three treatment groups: meglumine antimoniate plus allopurinol (Group A), meglumine antimoniate (Group B) or allopurinol (Group C). During the study, the dogs were examined before treatment (Day 0) and bimonthly thereafter until Day 180 (six months post-treatment onset). RESULTS: The three groups were scored over time according to the effects of treatment on clinical signs and clinical-pathological variables. Significant differences in clinical scores were observed between Group A and the other two groups, indicating the combined treatment was the most effective. After treatment, bone marrow cultures were positive for the parasite in 30.8% of dogs in some of the check ups (3 or 25% in Group A, 1 or 11.1% in Group B, and 4 or 80% in Group C). Our xenodiagnosis experiments revealed that 15.4% of treated dogs were still able to infect sand flies at some point after treatment (2 dogs or 16.6% in Group A, 2 or 22.2% in Group B and none in Group C). Only 7.7% of the entire study population could infect sand flies as from the second month post-treatment onset. CONCLUSION: The three treatment regimens tested significantly reduced the infectivity of dogs towards sand flies, thus diminishing the epidemiological risks of treated dogs both for human beings and other healthy dogs. Despite its low cure rate, the use of allopurinol after a course of leishmanicide treatment is proposed to keep dogs non-infectious during the disease transmission season (4-6 months in southern Europe). The authors are indebted to the owners of all the dogs participating in this study. Publication of the CVBD6 thematic series was sponsored by Bayer Animal Health GmbH. Sí

Whether the use of tumor necrosis factor antagonists increases the risk of infection remains a subject of open debate. Developing effective strategies of prevention and empirical treatment entails carefully establishing the etiology and prognosis of the infections.Analysis of the Spanish registry BIOBADASER (Feb-2000 to Jan-2006), a national drug safety registry of patients with rheumatic diseases.907 episodes of infection occurring in 6,969 patients were analyzed. The infection incidence observed was 53.09 cases/1,000 patients-years (CI 95% 49.69-56.66). The most frequent infections were skin infection (12.18 cases/1,000 patients-yrs), pneumonia (5.97 cases/1,000 patients-yrs), cystitis (3.92 cases/1,000 patients-yrs), tuberculosis (3.51 cases/1,000 patients-yrs) and arthritis (3.76 cases/1,000 patients-yrs). Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Salmonella spp. emerged as important pathogens. Varicella zoster virus and Herpes simplex virus caused most cases of viral infections. Mucocutaneous candidiasis accounted for most fungal infections. Mortality was increased in infected patients (log-rank test p0.0001). Pneumonia, sepsis, tuberculosis, abdominal infection and endocarditis were associated with significant attributable mortality.A significant number of bacterial, viral and fungal infections occurred in patients with rheumatic diseases treated with TNF antagonists. The information of this study can illuminate clinicians globally on how to address infection in this vulnerable group of patients.

Objective. To compare the safety and retention rate of TNF antagonists used in approved indications (AIs) and non-AIs. Methods. Analysis of the Spanish registry BIOBADASER 2.0 (February 2000 to October 2009). Patients were classified into AIs and off-label uses (OUs), according to the European Medicines Agency approval. Retention rates, incidence rates (IRs) and IR ratios (IRRs) of adverse events (AEs) with 95% CI were compared between uses, by log-rank test, cause-specific Cox regression models and generalized linear models with Poisson’s distribution. Results. First treatment with TNF antagonist was available in 5150 patients, of whom 4594 (89%) were AIs (2854 RA, 882 AS and 858 PsA) and 556 (11%) were OUs [437 chronic arthropathies in the spectrum of SpAs (CA) and 119 chronic immune-mediated diseases (CIDs)]. The IR of AE was largest in CID (649 events per 1000 patient-years) and lowest in PsA (250 events per 1000 patient-years). The occurrence of AEs was significantly associated with OU [IRR of CA vs RA 1.33 (95% CI 1.19, 1.49); IRR of CID vs RA 1.94 (95% CI 1.62, 2.31). The largest hazard ratio for discontinuation was for CID vs RA (1.33; 95% CI 1.02, 1.71) and especially vs AS (2.18; 95% CI 1.63, 2.90). Conclusions. OUs of TNF antagonists need a very close ascertainment of risk/benefit. The safety and retention pattern for CID is similar to that for RA and the pattern for CA resembles that of AS. This study shows an additional value of a national registry.

Objective To estimate the incidence of hospitalisation due to varicella zoster virus (VZV) infection in patients treated with tumour necrosis factor (TNF) antagonists for infl ammatory rheumatic conditions and to compare it with the expected rate in the general population. Methods Secondary data analysis was performed of two large databases: (1) the national registry of rheumatic diseases patients treated with biological agents (BIOBADASER); and (2) the national hospital discharge database Conjunto Minimo Basico de Datos al Alta Hospitalaria. Hospitalisations due to shingles or chickenpox were analysed. For each condition the incidence rate (IR) and the age and gender standardised IR per 100 000 person-years plus the standardised incidence ratio (SIR) and the standardised incidence difference (SID) were estimated. Results In patients exposed to TNF antagonists, the estimated IR of hospitalisation due to shingles was 32 cases per 100 000 patient-years (95% CI 14 to 78), the expected rate in the general population was 3.4 (95% CI 3.2 to 3.5), the SIR was 9 (95% CI 3 to 20) and the SID was 26 (95% CI 14 to 37). The estimated IR of hospitalisation due to chickenpox was 26 cases per 100 000 (95% CI 10 to 69), the expected rate was 1.9 (95% CI 1.8 to 2.0), the SIR was 19 (95% CI 5 to 47) and the SID 33 (95% CI 21 to 45). Conclusions Patients suffering rheumatic diseases exposed to TNF antagonists are hospitalised due to VZV infections signifi cantly more frequently than expected in the general population. Since the absolute IR of hospitalisations due to chickenpox and shingles is low in these patients, the implementation of risky preventive measures may not be justifi ed at present.

Objective To describe the risk of cancer in patients exposed to tumor necrosis factor (TNF) antagonists. Methods The following 2 clinical cohorts were studied: (1) BIOBADASER 2.0: a registry of patients suffering from rheumatic diseases exposed to TNF antagonists (2531 rheumatoid arthritis (RA), 1488 spondyloarthropathies, and 675 other rheumatic conditions); and (2) EMECAR: a cohort of 789 RA patients not exposed to TNF antagonists. Cancer incidence rates (IR) per 1000 patient-years and incidence rate ratios (IRR) were calculated for BIOBADASER 2.0 and EMECAR patients. The IR over time in BIOBADASER 2.0 patients was analyzed by joinpoint regression. The IRR was estimated to compare cancer rates in exposed versus nonexposed RA patients. Standardized incidence and mortality ratios (SIR, SMR) were also estimated. Risk factors for cancer in patients exposed to TNF antagonists were investigated by generalized linear models. Results The SMR for cancer in BIODASER 2.0 was 0.67 (95% CI: 0.51-0.86), and the SIR was 0.1 (95% CI 0.03-0.23). The IR in RA patients exposed to TNF antagonists was 5.8 (95% CI: 4.4-7.6), and the adjusted IRR was 0.48 (95% CI: 0.09-2.45). The IR in patients with previous cancer was 26.4 (95% CI: 4.1-171.5). Age, chronic obstructive pulmonary disease, and steroids were associated with a higher risk of developing cancer. The IR decreased after the first 4 months of exposure, without statistical significance. Conclusion Overall cancer and mortality rates in patients with rheumatic diseases exposed to TNF antagonists are no higher than in the background Spanish population. However special attention should be paid to elderly patients, those with previous cancers, and patients treated with steroids.

Conventional malaria diagnosis based on microscopy raises serious difficulties in weak health systems. Cost-effective and sensitive rapid diagnostic tests have been recently proposed as alternatives to microscopy. In Equatorial Guinea, a study was conducted to assess the reliability of a rapid diagnostic test compared to microscopy. The study was designed in accordance with the directives of the Standards for Reporting Diagnostic Accuracy Initiative (STARD). Peripheral thick and thin films for the microscopy diagnosis and a rapid immunochromatographic test (ICT Malaria Combo Cassette Test) were performed on under five-year-old children with malaria suspicion. The ICT test detected Plasmodium spp. infection with a sensitivity of 81.5% and a specificity of 81.9% while P. falciparum diagnosis occurred with a sensitivity of 69.7% and a specificity of 73.7%. The sensitivity of the ICT test increased with higher parasitemias. The general results showed little concordance between the ICT test and microscopy (kappa = 0.28, se: 0.04). In Equatorial Guinea, the ICT Malaria Combo Cassette Test has proven to be an acceptable test to detect high P. falciparum parasitemias. However, the decrease of sensitivity at medium and low parasitemias hampers that ICT can replace properly performed microscopy at present in the diagnosis of malaria in children. This study was funded by the Spanish International Cooperation Agency (AECI) and the Institute of Health Carlos III within the Network of Tropical Diseases Research Centers (RICET. R06/0021/0000). Sí

Objective. To estimate the incidence of early arthritis (EA) and of RA in adults (>16 yrs) in Spain. Methods. Primary care physicians were instructed in the detection of new cases using a checklist. All cases were evaluated at EA units (EAUs) within 15 days of detection. ACR criteria for the classification of RA were assessed every 6 months thereafter. Results. In an area covering 4 342 378 inhabitants over the age of 16 yrs, 2467 patients were referred to the EAU, of whom 1063 fulfilled EA criteria (43.1%). After 6 months, 362 patients fulfilled RA criteria. The estimated annual incidence of EA was 25/100 000 population (95% CI: 23, 26). The annual incidence of RA was 8.3 cases/100 000 (95% CI: 7.5, 9.2): 11.3/100 000 in women (95% CI: 10.0, 12.8), and 5.2/100 000 in men (95% CI: 4.3, 6.3). The incidence of RA increased with age in both sexes. At the 6 months’ assessment, 187 (51.7%) of the patients with RA were RF positive. The presentation of RA was mainly polyarticular (n ¼ 268; 74.0%). There were 701/1063 patients with EA who did not fulfil RA criteria by 6 months after the first rheumatologist visit. If all cases of undifferentiated arthritis (n ¼ 118; 17%) became RA, the incidence would be in the range of 10 cases/100 000 population. Conclusions. RA incidence in Spain is in the lower range of published data. The incidence of EA is about three times that of RA.

Objectives To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA). Methods We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI). Results The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm 3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)). Conclusions The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.

Objectives To analyse if using risk indices and PIXI scans jointly would reduce requirement for central DEXA to diagnose postmenopausal OP. Methods A stratified sample of postmenopausal women was selected: a random sample of 305 postmenopausal women from Primary care, and 200 consecutive postmenopausal women referred for central DXA measurement from tertiary care. Inclusion criteria: Caucasian female, age ≥50 yrs, and full menopause (amenorrhea ≥12 mo.). Exclusion criteria: previous diagnose of OP, previous treatment with OP drugs (calcium and/or vitamin D and/or estrogens for menopausal symptoms treatment were allowed) or steroids and other drugs related with low BMD, and institutionalized persons OR Steinbrocker’s functional grade 4. Informed consent was obtained. Four risk indices were calculated: SCORE, ORAI, OSIRIS, and OST. All participants underwent two different BMD measurements: a non-dominant heel BMD (PIXI Lunar, Software #50699, GE Corp.), and a central DXA of the hip and lumbar spine (Lunar Prodigy Advance, Software ENCORE 2006, PA+300274, GE Corporation). OP definition according to the WHO was used. Statistical analyses: The diagnostic utility was measured by ROC curves. We calculated the sensitivity and specificity for risk indices, PIXI, and all possible combinations. Logistic regression was performed to build a risk model with the presence or absence of osteoporosis at the central DEXA as dependent variable. The thresholds was established in 2 ways: 1) a cutoff point where the sensitivity and specificity are maximized, and 2) with two cutoff points, where both it sensitivity and specificity reached 90%. Results 505 Caucasian women with a mean (SD) 61 (8) yrs, were recruited. Median (p25-p75) scores for each risk index were: OST 1 (0-3), ORAI 10 (7-14), and SCORE 8 (6-11). The mean (SD) PIXI T-score of the calcaneus was -0.33 (1.14). The mean (SD) femoral neck T-score was -1.01 (1.05), total femur was -0.59 (1.19) and lumbar T-score was -1.18 (1.36). The prevalence of osteoporosis by central DXA was 20% (n=102), 19% (57) in primary care and 23% (45) in tertiary care. The combined algorithm PIXI + OST + SCORE was the greatest area under the curve obtained: 75% (95% CI, 71 to 79). Most favorable threshold for this algorithm stratified subjects into high, medium, and low risk according to 2 cutoff (-20 and -5, respectively), and the most favorable subsequent decision was referral for central DXA if the medium or high risk categories were reached. According to this algorithm (table) 11 (2.2%) false negatives were obtained, but 257 (52%) central DEXA were avoided and a 20 – 35% in costs could have been saved. Conclusions A triage based on a combined algorithm composed of PIXI + OST + SCORE reduces reduce the requirements of central DEXA a 52%, and may savings cost. Disclosure of Interest None Declared

Background Data on infections in patients exposed to biological therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other chronic inflammatory immune-mediated diseases (CIID). Objectives To describe and compare the risk of serious infections in RA and CIID patients on TNF antagonists or Rituximab (RTX) and to identify predictors of serious infections. Methods Data from the Spanish registry BIOBADASER 2.0 (2000-2011) were analyzed. RA or CIID patients >16 years on TNF antagonists (infliximab, adalimumab, etanercept) or RTX were selected. Only first treatment was considered in the analysis. CIID included: systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, poly/dermatomyositis, relapsing polychondritis, Sjogren’s syndrome, adult Still’s disease and vasculitis. For each group, incidence rate (IR) and mortality rate (MR) of serious infections with 95% confidence intervals were estimated. They were compared using incidence rate ratio (IRR) and mortality rate ratio (MRR).The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated according to the Spanish general population. Risk factors for serious infectious were assessed using generalized linear models with Poisson distribution. Results A total of 3,301 patients on TNF antagonists or RTX (95% RA patients and 5% CIID) were analyzed. RA patients were older, there were more women, reported more comorbidities and concomitant treatments compared with CIID patients. We found 331 and 39 serious infections in RA and CIID patients, respectively. The most frequent infections were located in the lower respiratory tract. IR of serious infections was higher in CIID patients, both with TNF antagonists or RTX, but it was only statistically significant in the TNF antagonists group (TABLE). A total of 23 patients on TNF antagonists (22 RA) and 2 with RTX (1 RA) died due to infections which was higher in CIID although it did not reach statistical significance [MRR-TNF antagonists ofCIID vs. RA patients1.6 (0.02, 11.91), MRR-RTX of CIID vs. RA 1.48 (0.09, 23.58)]. Both the SIR and the SMR were increased compared with Spanish general population. In a subanalysis of 292 RA and 16 CIID patients who switched from TNF antagonists to RTX, infections were more frequent in CIID [IRR 1.87 (0.48, 7.24) than in RA (IRR 1 (0.64, 1.59)] but without reaching statistical significance.Multivariate analysis showed that higher age, disease duration, COPD, interstitial lung disease, renal insufficiency, hypertension and concomitant corticosteroids were risk factors for serious infections. In the final multivariate model, adjusted for confounding variables, CIID were associated with a higher risk of infection [IRR 1.96 (1.06, 3.05)] compared with RA. View this table: Table 1. Incidence rate of serious infections Conclusions Serious infections in patients on TNF antagonists or RTX are more frequent in CIID than in RA patients. This remark must be taken into account when a risk/benefit balance for off-label use is made. Disclosure of Interest None Declared

WOS: 000257144900009, PubMed: 18325087, Introduction We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease- modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. Methods The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. Results Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. Conclusion In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.