Use of risk chart algorithms for the identification of psoriatic arthritis patients at high risk for cardiovascular disease: findings derived from the project CARMA cohort after a 7.5-year follow-up period.

OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.

Serum Advanced Glycation End Products and Their Soluble Receptor as New Biomarkers in Systemic Lupus Erythematosus.

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE-sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Cancer risk with biologic and targeted synthetic DMARDs in patients with rheumatic diseases and previous malignancies: Results from the BIOBADASER register.

OBJECTIVE: to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95 % confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared. RESULTS: A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95 % CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95 % CI 0.2-1.7)], anti-CD20 [0.4(95 % CI 0.1-1)], or anti-IL6 [1.1(95 % CI 0.5-2.4)], anti-CTLA-4 [1.5 (95 % CI 0.7-3.1) or anti-IL17 [0.7 (95 % CI 0.2-2.4) versus TNFi therapy. CONCLUSIONS: We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.

Real-world effectiveness and persistence of reference etanercept versus biosimilar etanercept GP2015 among rheumatoid arthritis patients: A cohort study.

Although several randomized clinical trials have confirmed that there is no difference in efficacy between etanercept and its biosimilar versions in the treatment of rheumatoid arthritis (RA), limited real-world evidence is available. We conducted a cohort study to compare the effectiveness and treatment persistence between the reference etanercept (ETN) and the biosimilar GP2015 in RA patients in a real-life setting. Adults with a diagnosis of RA who initiated treatment with ETN or GP2015, between January 2007 and December 2019, were included. The follow-up period was 52 weeks. The primary outcome was the mean of change in the DAS28-CRP values and the adjusted mean difference from baseline to 52 weeks between ETN and GP2015. Other effectiveness endpoints assessed were the rate of patients who achieved remission or low disease activity (LDA) at week 52, who showed a reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 and rate of good responder patients (those meeting both effectiveness measures) at week 52. Treatment effectiveness over time (baseline, 26 and 52 weeks) was compared between the ETN and GP2015 groups using mixed effects models. Treatment persistence (probability of maintaining the same treatment over time) was also evaluated and shown using Kaplan-Meier survival curves. A total of 115 RA patients were included (ETN, n = 90; GP2015, n = 25). No differences were observed in the primary outcome: DAS28-CRP score decreased from baseline to week 52 [5.1 to 2.7 (mean of change -2.37) in ETN group and 5.0 to 2.2 (mean of change -2.84) in GP2015 group, p-value = 0.372] and the adjusted mean difference was -0.37 (-1.03 to 0.29). No differences were also observed in the other effectiveness endpoints assessed among patients treated with ETN or GP2015: rate of patients who achieved remission (54.1% vs. 66.7%, p-value = 0.303) and LDA (71.6% vs. 80.9%, p-value = 0.391) at week 52, reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 (75.6% vs. 80.9%, p-value = 0.613) and rate of good responder patients (58.1% vs. 76.1%, p-value = 0.202). Drug survival was 82% and 80% for ETN and GP2015, respectively (log-rank p-value = 0.804). Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting.

Clinical Patterns and Follow-Up of Inflammatory Arthritis and Other Immune-Related Adverse Events Induced by Checkpoint Inhibitors. A Multicenter Study.

Objectives: To describe different clinical patterns of rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICI) and their rheumatic and oncologic outcomes. Methods: We classified clinical syndromes according to five different categories: non-inflammatory arthralgias (NIA), rheumatoid arthritis (RA)-like, psoriatic arthritis (PsA)-like, polymyalgia rheumatica (PMR)-like, and a miscellaneous group of patients with other syndromes. We conducted a baseline visit and then follow-up in order to determine their clinical pattern, treatment response, and outcome. Results: We included 73 patients (64% male) with a mean age of 66.1 ± 11.6 years. Main underlying diagnosis was lung carcinoma in 29 (39%) patients, melanoma in 20 (27%), and renal-urothelial cancer in 11 (15%). Main ICI included Pembrolizumab in 24 (32%), Nivolumab 17 (23%), and Atezolizumab 7 (9 %). Seventeen out of seventy-three patients had an underlying rheumatic disease before ICI treatment. Fourteen patients developed other irAEs before or simultaneously with rheumatic syndromes. Main rheumatic irAEs included: RA-like in 31 (42.4%), NIA in 19 (26.0%), PMR-like in 10 (13.7%), and PsA-like in 5 (6.8%), among others. Median time from ICI to irAEs was 5 months (IQR 3-9). Those patients who received combined therapy, had a trend for an earlier presentation than those who received monotherapy (4.3 months IQR 1.85-17 vs. 6 months IQR 3-9.25, p = NS). Mean follow-up time was 14.0 ± 10.8 (SD, months). At the last visit, 47 % were taking glucocorticoids and 11% DMARD therapy. At the last visit, 13 (17.8%) patients remained with persistent arthritis, 19 (26%) had intermittent flares, and 39 (53.4%) had a self-limited pattern. Only in 15.1% of patients ICI therapy was discontinued. Conclusions: We described different patterns according to treatment and irAEs. Combined ICI therapy had an earlier onset of symptoms. Patients who presented as RA-like, had a higher risk of persistent arthritis. After a mean follow-up of more than 1 year, one-fifth of the patients remained with persistent arthritis and 11% required DMARD therapy.

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. FINDINGS: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. INTERPRETATION: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems. FUNDING: The Instituto de Salud Carlos III.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Corrigendum: Impact of Non-Persistence on Healthcare Resource Utilization Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study.

[This corrects the article DOI: 10.3389/fphar.2021.752879.].

The synovial and blood monocyte DNA methylomes mirror prognosis, evolution, and treatment in early arthritis.

Identifying predictive biomarkers at early stages of inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes (MOs) and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) MOs in a prospective cohort of patients with early inflammatory arthritis. DNA methylation profiles of undifferentiated arthritis (UA) blood MOs exhibited marked alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF MOs after comparing patients with UA grouped by their future outcomes, i.e., good versus poor. Patient profiles in subsequent visits revealed a reversion toward a healthy level in both groups, those requiring disease-modifying antirheumatic drugs and those who remitted spontaneously. Changes in disease activity between visits also affected DNA methylation, which was partially concomitant in the SF of UA and in blood MOs of patients with rheumatoid arthritis. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity, and treatment efficacy for the personalized clinical management of early inflammatory arthritis.

Impact of Non-Persistence on Healthcare Resource Utilization and Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study.

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (-€193.99 [195.88] vs. -€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. -€10.90 [157.42], p < 0.001) and total costs (€3268.90 [4821.55] vs. -€334.67 (905.44), p < 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.

Body Mass Index and Disease Activity in Chronic Inflammatory Rheumatic Diseases: Results of the Cardiovascular in Rheumatology (Carma) Project.

OBJECTIVE: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. METHODS: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. RESULTS: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (ß = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (ß = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (ß = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. CONCLUSIONS: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients.

Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study.

BACKGROUND: Vagus nerve stimulation delivered with an implanted device has been shown to improve rheumatoid arthritis severity. We aimed to investigate the safety and efficacy of non-invasive stimulation of the auricular branch of the vagus nerve for the treatment of patients with moderately to severely active rheumatoid arthritis. METHODS: This prospective, multicentre, open-label, single-arm proof-of-concept study enrolled patients aged 18-80 years with active rheumatoid arthritis who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and up to one biological DMARD. Biological DMARDs were stopped at least 4 weeks before enrolment and concomitant use was not allowed during the study. All eligible participants were assigned to use a non-invasive, wearable vagus nerve stimulation device for up to 30 min per day, which delivered pulses of 20 kHz. Follow-up visits occurred at week 1, week 2, week 4, week 8, and week 12 after the baseline visit. The primary endpoint was the mean change in Disease Activity Score of 28 joints with C-reactive protein (DAS28-CRP) at week 12 compared with baseline. Secondary endpoints included the mean change in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the proportion of patients with a minimal clinically important difference of 0·22 on HAQ-DI, the proportion achieving American College of Rheumatology (ACR) 20, ACR50, and ACR70 response, and safety analysis. This study is registered with ClinicalTrials.gov (NCT04116866). FINDINGS: Of 35 patients screened for eligibility, 30 (86%) were enrolled at six centres in Spain between Dec 27, 2018, and Oct 24, 2019, of whom 27 (90%) completed the week 12 visit. The mean change in DAS28-CRP at 12 weeks was -1·4 (95%CI -1·9 to -0·9; p<0·0001) from a mean baseline of 5·3 (SD 1·0). 11 (37%) of 30 patients reached DAS28-CRP of 3·2 or less, and seven (23%) patients reached DAS28-CRP of less than 2·6 at week 12. The mean HAQ-DI change was -0·5 (95%CI -0·7 to -0·2; p<0·0001) from a mean baseline of 1·6 (SD 0·7), and 17 (57%) patients reached a minimal clinically important difference of 0·22 or more. ACR20 responses were reached by 16 (53%) patients, ACR50 responses by 10 (33%) patients, and ACR70 by five (17%) patients. Four adverse events were reported, none of which were serious and all of which resolved without intervention. INTERPRETATION: Use of the device was well tolerated, and patients had clinically meaningful reductions in DAS28-CRP. This was an uncontrolled, open-label study, and the results must be interpreted in this context. Further evaluation in larger, controlled studies is needed to confirm whether this non-invasive approach might offer an alternative treatment for rheumatoid arthritis. FUNDING: Nesos.

Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment: data from the BIOBADASER III register.

OBJECTIVES: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. RESULTS: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. CONCLUSION: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.

Correlation of fatigue with other disease related and psychosocial factors in patients with rheumatoid arthritis treated with tocilizumab: ACT-AXIS study.

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ±â€Š12.5 years, disease duration 8.7 ±â€Š7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ±â€Š4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ±â€Š1.0 at baseline to 2.7 ±â€Š1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ±â€Š11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Retraso diagnóstico y terapéutico de la artritis reumatoide y su relación con dispositivos asistenciales en Catalunya. Estudio AUDIT / Diagnostic and therapeutic delay of rheumatoid arthritis and its relationship with health care devices in Catalonia. The AUDIT study

OBJETIVO: Analizar el retraso diagnóstico y terapéutico en pacientes con AR de reciente comienzo en 19 centros de Catalunya. MÉTODOS: Encuesta epidemiológica en 183 pacientes en que se cuantificaron los tiempos en relación con el retraso diagnostico midiendo: 1) aparición del primer síntoma hasta la primera visita a Reumatología; 2) desde la derivación hasta la primera visita de Reumatología; 3) entre aparición del primer síntoma hasta el diagnóstico, y 4) entre aparición del primer síntoma hasta el inicio del primer FAME. Se definió la existencia de 6 dispositivos asistenciales diferenciados. RESULTADOS: El tiempo medio desde el inicio de los síntomas hasta la instauración de un FAME en pacientes con AR en Catalunya es muy largo (11 meses). Pacientes atendidos en dispositivos como consultas de AR, consultas especializadas en atención primaria y sobre todo en consultas de artritis de inicio son tratados de manera más temprana con FAME. Conclusión. La existencia de determinados dispositivos asistenciales es fundamental para mejorar la atención precoz en la AR

OBJECTIVE: Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. METHODS: We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. RESULTS: The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. Conclusion. the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients