Functional respiratory impairment and related factors in patients with interstitial pneumonia with autoimmune features (IPAF): Multicenter study from NEREA registry.

BACKGROUND: The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. METHODS: A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. MAIN OUTCOME: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. STATISTICS: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR) and [CI]). RESULTS: 79 IPAF were included, with a mean and a maximum follow-up of 3.17 and 12 years respectively. Along the study, 77.2% received treatment (52 glucocorticoids, 25 mycophenolate, 21 azathioprine, 15 rituximab and 11 antifibrotics). IR was 23.9 [19.9-28.8], and 50% of IPAF developed functional respiratory impairment after 16 months from its diagnosis. Multivariate analysis: usual interstitial pneumonia (UIP) had poorer prognosis compared to non-specific interstitial pneumonia (NSIP) (p = 0.001). In NSIP, positive ANA, increased the risk of poor prognosis. In UIP, glucocorticoids (HR: 0.53 [0.34-0.83]), age (HR: 1.04 [1.01-1.07]), and Ro-antibodies (HR: 0.36 [0.19-0.65]) influenced the prognosis. CONCLUSIONS: IPAF have functional impairment during the first years of disease. Factors predicting deterioration differ between radiographic patterns. Our real-life study suggests the potential benefit of particular therapies in IPAF.

Severe COVID-19 in patients with immune-mediated rheumatic diseases: a stratified analysis from the SORCOM multicenter registry.

OBJECTIVES: To evaluate risk factors for severe Coronavirus Disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis. METHODS: An observational, cross-sectional multicenter study was performed. Patients from 10 Rheumatology departments in Madrid who presented with SARS-CoV-2 infection between Feb 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (sociodemographic, clinical and treatments), using logistic regression analyses. RESULTS: 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age and comorbidities such as diabetes mellitus, hypertension and obesity were associated with severe COVID-19. Corticosteroid doses over 10 mg/day, rituximab, sulfasalazine and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, p<0.001), although there were no differences in overall severity in the multivariate analysis. CONCLUSIONS: This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-TNF therapy were not associated with worse outcomes.

EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis.

BACKGROUND: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses. OBJECTIVES: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain. METHODS: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously. RESULTS: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9). CONCLUSION: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.

Mortality rate in rheumatoid arthritis-related interstitial lung disease: the role of radiographic patterns.

BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19. METHODS: An observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission. RESULTS: The study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model. CONCLUSION: Our results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases.

BACKGROUND: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. METHODS: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. RESULTS: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. CONCLUSION: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.

Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related interstitial lung disease: data from the NEREA Registry.

OBJECTIVES: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.

Hip Fracture in Nonagenarians: Characteristics and Factors Related to 30-Day Mortality in 1177 Patients.

BACKGROUND: The number of nonagenarian patients with hip fracture is increasing. The goals of this study were to describe the characteristics and in-hospital course of a cohort of 1177 nonagenarians admitted for hip fracture compared with younger patients and to identify risk factors for 30-day mortality after admission. METHODS: This is a retrospective observational cohort study including patients aged 65 years or older admitted for hip fracture during various periods from February 1997 to December 2016. We defined 3 age groups: 65-79, 80-89, and 90 years and older. We included sociodemographic variables, baseline functional status, comorbidities, fracture and surgical characteristics, postoperative complications, length of stay, and in-hospital and 30-day mortality. Multiple logistic regression analysis was used to study risk factors for 30-day mortality in surgically treated nonagenarians. RESULTS: Nonagenarians were more likely to be women and to have dementia and heart disease. Some 72% walked independently before the fracture. The most relevant treatable risk factor for 30-day mortality in nonagenarians (in terms of higher odds ratio [OR]) was developing respiratory infection (OR: 4.56, 95% confidence interval [CI]: 2.73-7.63). Better prefracture functional status (higher Katz score; OR: 0.83, 95% CI: 0.74-0.92) and spinal anesthesia (OR: 0.19, 95% CI: 0.05-0.68) decreased risk of 30-day mortality. CONCLUSIONS: Nonagenarian patients with hip fracture differ significantly from younger patients concerning clinical characteristics, medical complications, and in-hospital and 30-day mortality rates. We identified several variables on which we could act to reduce 30-day mortality, such as respiratory infection, electrolyte disorders, polypharmacy, cardiac arrhythmia, and spinal anesthesia.

Validation of a Quality of Life Instrument in Spanish Patients With Rheumatic Diseases: The Rosser Classification System.

OBJECTIVE: The aim of this study was to assess the reliability and validity of the Spanish version of the Rosser classification system for disease states in patients with musculoskeletal disorders. METHODS: Our study was based on a questionnaire validation design. Patients were attended at an outpatient rheumatology clinic at Hospital Clínico San Carlos, Madrid, Spain. The Rosser classification system was completed by the physician from the research team (PMQ) and by the patient (HMQ). Criterion standards: The EuroQol-5D for the HMQ and the physician global estimate (DOCGL) for the PMQ. Internal consistency reliability was assessed using Cronbach α. Test-retest reliability and interobserver reliability were analyzed using the intraclass correlation coefficient. The criterion validity between HMQ and EuroQol-5D and between PMQ and DOCGL was assessed using the Spearman correlation coefficient. RESULTS: The full analysis was based on 4 samples of patients (104 to 266 patients), most of whom were middle-aged women. For HMQ, Cronbach α was 0.70. Test-retest reproducibility was 0.7. With respect to criterion validity, significant correlations in the expected direction were observed. For PMQ, Cronbach α was 0.70, indicating excellent intraobserver and interobserver reliability. With respect to criterion validity, strong correlations were observed between the PMQ and the DOCGL. CONCLUSIONS: The Rosser classification system showed satisfactory reliability and suitable criterion validity for patients with musculoskeletal disorders. The instrument seems to be suitable for clinical decision making and research.

Severe adverse drug reactions to biological disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis in clinical practice.

OBJECTIVES: Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. METHODS: A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included. PRIMARY OUTCOME: discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models. RESULTS: We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs. CONCLUSIONS: Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.

Treatment with methotrexate and risk of relapses in patients with giant cell arteritis in clinical practice.

OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.

Disease Remission in Children and Adolescents with Intermediate Uveitis: A Survival Analysis.

PURPOSE: To report the incidence rate (IR) of remission in pediatric noninfectious intermediate uveitis (IU). METHODS: Longitudinal retrospective cohort study, including 19 patients (32 eyes) between 1985 and 2014, followed-up until loss or January 2016. Remission was defined following the Standardization of Uveitis Nomenclature workshop criteria, prolonged remission as a remission spanning 12 months and until the end of follow-up, and relapse as recurrence of inflammatory activity in an eye in remission. RESULTS: Median follow-up time was 6.3 years. IRs (95% confidence interval) for remission, relapse, and prolonged remission were 18.6 (13.1-26.5), 32.3 (20.6-50.7), and 6.7 (3.8-11.9) episodes per 100 eye-years, respectively. 48% of eyes relapsed in the first year following remission. 25 and 50% of eyes achieved prolonged remission after 5 and 10 years of follow-up, respectively. CONCLUSIONS: Inflammatory relapses may be frequent in noninfectious IU affecting children and adolescents, appearing early after remission. Also, prolonged remission seems infrequent, being achieved late during follow-up.

Long-term continuation of methotrexate therapy in giant cell arteritis patients in clinical practice.

OBJECTIVES: To assess the long-term continuation of methotrexate (MTX) in a cohort of patients with giant cell arteritis (GCA) in daily clinical practice. Factors associated with its discontinuation rate were also investigated. METHODS: A longitudinal study from 1991-2014, was performed. GCA patients with MTX and followed-up in a rheumatology outpatient clinic of Madrid during the study period were included. PRIMARY OUTCOME: discontinuation of MTX due to: adverse drug reactions (ADR moderate and severe); inefficacy; sustained clinical response; patient decision. Covariables: sociodemographic, clinical and therapy. Incidence rates (IR) of MTX discontinuation per 100 patient-years with their 95% confidence interval (CI) were estimated using survival techniques. Factors associated to specific discontinuation causes were analysed using Cox models. RESULTS: We included 108 patients (244 patient-years). The IR was 37.2 [30.3-45.7]. The IR due to ADR, severe ADR, sustained clinical response and inefficacy was 20.8 [15.8-27.4]; 5.7 [3.3-9.6]; 8.2 [5.3-12.7] and 2.8 [1.3-6.0], respectively. Regarding multivariate analysis, younger patients, baseline cardiovascular disease, taking more glucocorticoids and lower initial doses of MTX were associated to a higher discontinuation rate due to inefficacy. Factors influencing the suspension due to ADRs were: older age, baseline. Chronic obstructive pulmonary disease, higher baseline erythrocyte sedimentation rate, several specific clinical patterns at diagnosis, and higher maximum dose of MTX during the follow up. In the final model for sustained clinical response older patients and more recurrences were independently associated to less discontinuation rate. CONCLUSIONS: We provide further data of the potential safety of long-term MTX in the management of GCA. We have also found several factors influencing the continuation of MTX.

Dose down-titration of biological DMARDs in patients with rheumatoid arthritis over time and in daily clinical practice.

OBJECTIVES: To describe and compare dosing optimisation in biological DMARDs (bDMARDs) and relapses after that, in a cohort of rheumatoid arthritis (RA) during clinical practice. METHODS: Observational retrospective longitudinal study of RA patients taking bDMARDs from December 1999 to November 2013. Optimisation was defined as a 15% decrease in dose either reducing single dose or separating dose interval administration, for at least 4 times the recommended period between dosages. Relapse was defined as suspension or starting again with the recommended dose after optimisation. Incidence rates (IR) per 100 patient-years were estimated using survival techniques. Cox multivariate models were conducted to compare bDMARDs expressed in hazard ratios (HR) and confidence intervals [95%CI]. RESULTS: 443 patients and 752 different courses of bDMARDs treatments were included. We observed 146 optimisations with an IR of 8.1. The HR of optimisation in: a) adalimumab, etanercept and rituximab compared to infliximab was 1.56 [1.01-2.4], 1.5 [0.9-2.4] and 0.6 [0.3-1.4], respectively; b) adalimumab, etanercept compared to rituximab were 2.3 [1.2-4.5] and 2.2 [1.2-4.3]. There were no statistically significant differences between adalimumab and etanercept. Following optimisation, 36% relapsed (78% due to disease activity). The IR related to disease activity was 6.3, and was lower for adalimumab and etanercept compared to infliximab (HR: 0.42; [0.19-0.94]; HR: 0.34; [0.13-0.89], respectively). There were no statistically significant differences between etanercept and adalimumab. No patients on rituximab relapsed. CONCLUSIONS: Optimisation was similar between adalimumab and etanercept, and was lower for infliximab and rituximab. After optimisation, rituximab did not relapse, but infliximab did with the highest hazard.

Treatment in rheumatoid arthritis and mortality risk in clinical practice: the role of biologic agents.

OBJECTIVES: To assess the mortality rate (MR) and the mortality risk of a rheumatoid arthritis (RA) inception cohort, with and without biologic agents (BAs). Other factors associated to mortality were also investigated. METHODS: Retrospective longitudinal study of RA patients, attending the rheumatology outpatient clinic of a tertiary Hospital (Madrid), collected over 5 years (2000-2004), and followed from the diagnosis of RA up to the patients' death, lost to follow-up or September 2013. The dependent variable was death and the independent variable was exposure to BAs. Covariables: sociodemographic, clinical and therapy variables. MR was expressed per 1,000 patient-years with the 95% confidence interval [CI]. BA influence on MR was analysed by multivariable Cox models. Clinical and therapy variables were used in a time-dependent manner. The results are expressed in hazard ratio (HR) and [CI]. RESULTS: We included 576 patients and 711 courses of therapy. 19.6% were taking BA, 86% disease-modifying anti-rheumatic drugs (DMARDs) (70% on methotrexate - MTX), and 12% were untreated. There were 133 deaths during 4,981.64 patient-years at risk. The MR for BA was 12.6 [6-26], for DMARDs was 22.3 [18.4-27.1], and for those without treatment was 89.1 [61.9-128.2]. The adjusted HR for mortality in those exposed to BA versus those not exposed was 0.75 [0.32-1.71]). Other variables independently associated with mortality were: age, rheumatoid factor, hospital admissions, Health Assessment Questionnaire (HAQ), and MTX use (HR: 0.44 [0.29-0.66]). CONCLUSIONS: BAs and standard DMARDs are more effective in decreasing mortality compared to no therapy. Patients exposed to Bas were not associated with a significant increase or decrease in mortality when compared to patients with non-biological DMARDs. The use of MTX remains the only drug that has independently shown a beneficial effect on mortality.

Influence of patient personality in the treatment of rheumatoid arthritis.

Individualized treatment of rheumatoid arthritis (RA) based on genetic/serologic factors is increasingly accepted. Moreover, patients are more actively involved in the management of their disease. However, personality has received little attention with respect to perception of the need and adherence to treatment. Our objective was to evaluate whether patient personality was associated with the acceptance or rejection of more aggressive early treatment. We performed a cross-sectional study in two hospitals with early arthritis clinics where sociodemographic, clinical, and therapeutic variables are systematically recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related Control Scale. Aggressive treatment was considered if patients received more than two DMARDs or biological agents during the first year of follow-up. Multivariate logistic regression analysis was performed to determine predictors of aggressive treatment. One hundred seventy-six RA patients were included (80 % women, disease begin median age 55 years). Treatment was considered aggressive in 57.9 % of the sample. Scores were high in extraversion in 50.8 % of patients, neuroticism in 29.5 % and psychoticism in 14.7 %. Neuroticism was the only factor associated with aggressive treatment, which was less probable (p = 0.04, OR = 0.40). Neuroticism also decreased the possibility of receiving a combination of biologics and DMARDs (p = 0.04, OR = 0.28). Patients with high scores on neuroticism are more worried, obsessive and hypochondriac, leading them to reject more aggressive therapy. It is important to educate about their disease so that they will accept more aggressive approaches in clear cases of poor outcome.

The rs3771863 single nucleotide polymorphism of the TACR1 gene is associated to a lower risk of sicca syndrome in fibromyalgia patients.

OBJECTIVES: Fibromyalgia (FM) has been associated with affective spectrum disorders and other chronic pain disorders, which tend to co-occur in individuals and co-aggregate among families. The objective of our study was to investigate the genetic risk factors associated with the presence of related symptoms and with disease severity in subjects affected with FM. METHODS: Two independent cohorts of subjects diagnosed with FM according to the 1990 ACR criteria were studied. A genetic array composed of 320 single nucleotide polymorphisms (SNPs) was analysed in a discovery cohort comprised by 564 patients, and the most suggestive variants were genotyped in a replication cohort, comprised by 397 subjects. The associated conditions and related symptoms analysed were: the presence of depression, sleep disorders, headache, myofascial syndrome, irritable bowel syndrome, chronic fatigue syndrome, vertiginous syndrome, chronic cystitis, and sicca syndrome. FM severity was assessed by the Fibromyalgia Impact Questionnaire and the Hospital Anxiety and Depression Scale. Analyses were adjusted by elapsed time from pain onset, and a meta-analysis was performed to pool the results. RESULTS: Minor allele of the rs3771863 SNP from the TACR1 gene showed a significant association with a lower risk of sicca syndrome (pooled and adjusted OR 0.56, [95%CI 0.42-0.76], p=0.00022). CONCLUSIONS: Our findings indicate a role of the TACR1 gene in the development of sicca syndrome in subjects affected with FM.