Real-World Persistence and Treatment Patterns in Patients with Psoriatic Arthritis Treated with Anti-IL17 Therapy in Spain: The PerfIL-17 Study.

INTRODUCTION: Given the growing interest and use of interleukin-17 inhibitors (anti-IL17) for the treatment of psoriatic arthritis (PsA), an observational study has been conducted to characterize the patient profile, treatment patterns, and persistence of ixekizumab or secukinumab in patients with PsA receiving them as first anti-IL17. METHODS: This is a multicenter retrospective study, conducted at eight Spanish hospitals where data from adult patients with PsA were collected from electronic medical records. Three cohorts of patients, initiating treatment with an anti-IL17 [secukinumab 150 mg (SECU150), secukinumab 300 mg (SECU300), or ixekizumab (IXE)] between January 2019 and March 2021, were included. Demographic and clinical patient characteristics, treatment patterns, and persistence were analyzed descriptively. Continuous data were presented as mean [standard deviation (SD)] and categorical variables as frequencies with percentages. Persistence rates at 3, 6, and 12 months were calculated. RESULTS: A total of 221 patients with PsA were included in the study [SECU150, 103 (46.6%); SECU300, 38 (17.2%); and IXE, 80 (36.2%)]. Treatment patterns differed by clinical characteristics: SECU150 was initiated more frequently in patients with moderate PsA and less peripheral joint involvement, while patients on SECU300 included those with a higher rate of enthesitis and active skin psoriasis, and patients on IXE showed a longer time since PsA diagnosis, more frequent comorbidities, joint involvement, and diagnosed skin psoriasis. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) were previously administered in 88.2% of patients and biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were administered in 72.9%. The mean number of previous b/tsDMARDs was 2.4 (SD 1.5) in the IXE cohort, 1.7 (SD 0.9) in the SECU300 cohort, and 1.6 (SD 1.0) for those in the SECU150 cohort. The global persistence on all anti-IL17 was 97.2%, 88.4%, and 81.0% at 3, 6, and 12 months, respectively. The most frequent reason for discontinuation across the three cohorts was lack of effectiveness (16.7%; 37/221). CONCLUSIONS: Most of the patients with PsA treated with anti-IL17 in Spain had moderate to severe disease activity, high peripheral joint and skin involvement, and had received previous b/tsDMARDs. More than 80% of patients with a 1-year follow-up persisted on anti-IL17, with the highest rate observed in the IXE cohort, followed by the SECU150 then SECU300 cohorts.

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson's disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study.

Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

INTRODUCTION: Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. METHODS: This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24 weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24 weeks. RESULTS: Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5 years). The median time from PsA diagnosis to starting IXE was 7.7 years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104 weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12 weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24 weeks (p = 0.004). CONCLUSIONS: PsA patients treated with IXE in a real-world setting show high treatment persistence through 104 weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. RETROSPECTIVELY REGISTERED: Date of registration: 25th May 2021.

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms.

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis.

OBJECTIVE: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted 'yes' (yes/no). RESULTS: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients' risk management. CONCLUSIONS: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis / Documento de expertos sobre el uso de terapia combinada de metotrexato con terapias biológicas o terapias dirigidas a pacientes con artritis reumatoide

Objective: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). Methods: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted ‘yes’ (yes/no). Results: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients’ risk management. Conclusions: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.(AU)

Objetivo: Desarrollar recomendaciones sobre el uso de metotrexato (MTX) en combinación con medicamentos modificadores de la enfermedad (DMARD) biológicos (b) o sintéticos específicos (ts) en la artritis reumatoide (AR). Métodos: Se seleccionaron 11 expertos en AR. Dos coordinadores formularon 13 preguntas sobre la terapia combinada de MTX con bDMARD o tsDMARD. Se realizó una revisión sistemática para responder las preguntas. Se establecieron criterios de inclusión y exclusión, así como las estrategias de búsqueda (se realizaron búsquedas en Medline, Embase y la Biblioteca Cochrane hasta enero de 2019). Dos revisores seleccionaron los artículos y recopilaron datos. Simultáneamente, se evaluaron los resúmenes de las reuniones EULAR y ACR. Con base en esta evidencia, los coordinadores propusieron recomendaciones preliminares que los expertos discutieron y votaron en una reunión de grupo nominal. El nivel de evidencia y el grado de recomendación se establecieron utilizando el Centro de Oxford para Medicina Basada en Evidencia y el nivel de acuerdo con un Delphi. El acuerdo se estableció si al menos el 80% de los expertos votaron «sí» (sí/no). Resultados: La revisión sistemática recuperó 513 citas, de las cuales finalmente se incluyeron 61. Se generaron, votaron y aceptaron un total de 10 recomendaciones. El nivel de acuerdo fue muy alto en todas ellas y se logró en la primera ronda de Delphi. Las recomendaciones finales cubren aspectos como la dosis óptima de MTX, la estrategia de reducción o la gestión del riesgo de los pacientes. Conclusiones: Este documento está destinado a ayudar a los médicos a resolver preguntas clínicas habituales y facilitar la toma de decisiones al tratar a pacientes con AR con MTX, en combinación con bDMARD o tsDMARD.(AU)

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review.

OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. METHODS: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. RESULTS: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. CONCLUSION: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.

BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis.

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis.

OBJECTIVE: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted 'yes' (yes/no). RESULTS: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients' risk management. CONCLUSIONS: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.

Norma de calidad para el manejo del paciente con artritis psoriásica: proyecto QUANTUM / Quality standard for the management of patients with psoriatic arthritis: QUANTUM Project

OBJETIVO: Generar una norma de calidad para el manejo del paciente con artritis psoriásica (APs). MÉTODOS: Metodología cualitativa que incluyó: 1) dos grupos focales (uno con pacientes con APs y otro con especialistas no reumatólogos implicados en su cuidado); 2) revisión de la literatura publicada sobre documentos en el ámbito de la calidad asistencial en APs; 3) reunión de grupo nominal donde 15 expertos reumatólogos generaron, de forma consensuada, una serie de criterios de calidad así como fórmulas o medidas objetivas cuantificables para evaluarlas; 4) Delphi para establecer la factibilidad, prioridad y grado de acuerdo con los criterios de calidad, y 5) generación de estándares de calidad y sus atributos. Se realizó un análisis descriptivo de los resultados. RESULTADOS: Se generaron 59 estándares de calidad, 18 de los cuales de cumplimiento obligatorio, agrupados en 4 bloques según unos objetivos específicos: 1) acortar el tiempo hasta el diagnóstico (n=6); 2) optimizar el manejo de la enfermedad (n=26); 3) mejorar la colaboración multidisciplinar (n=9), y 4) mejorar la monitorización (n=18). Para evaluar el cumplimiento de estos estándares en muchos casos se revisarán las historias clínicas. Otras fuentes serán la memoria del servicio y del hospital así como los buscadores bibliográficos. En cuanto al nivel de exigencia a la hora de considerar por cumplido el estándar, algunos son de tipo sí/no, otros están desde el 50 al 100%, y en este rango muchos en el 80%. CONCLUSIONES: Esta norma de calidad debe ayudar en la mejora de la calidad de atención para el paciente con APs

OBJECTIVE: To generate a quality standard for the management of patients with psoriatic arthritis (PsA). METHODS: We employed qualitative methodology that included: 1) Two focus groups (one with patients with PsA and another with non-rheumatologist specialists involved in the care of PsA patients); 2) A narrative literature review of published documents related to the quality of care in PsA; 3) A nominal group meeting in which 15 expert rheumatologists generated and reached a consensus on a series of quality criteria, as well as formulas or quantifiable objective measures to evaluate them; 4) The Delphi method to establish the feasibility, priority and agreement with the quality criteria; 5) A final generation of standards of care and their attributes. A descriptive analysis of the results was carried out. RESULTS: A total of 59 standards of care was generated, 18 of mandatory compliance, grouped into 4 blocks according to specific objectives: 1) early diagnosis (n=6); 2) optimizing the management of the disease (n=26); 3) multidisciplinary collaboration (n=9); 4) monitoring improvement (n=18). To assess compliance with these standards of care, in many cases, the medical records will be reviewed. Other sources will be the records of the service and hospital and bibliographic databases. Regarding the level of compliance, for some of the standards of care this is yes/no; for others, compliance ranges from 50% to 100% and, in this range, in many cases, compliance was 80%. CONCLUSIONS: This set of standards of care should help improve quality of care in PsA patients

Role of IRF5 in the pathogenesis of immunoglobulin-A vasculitis.

OBJECTIVES: Interferon regulatory factor 5 (IRF5) is a major regulator of type I interferon induction and is also critical to produce pro-inflammatory cytokines. An influence of IRF5 genetic variants on the increased risk of immune-mediated diseases has been described. Accordingly, we aimed to evaluate the implication of IRF5 in the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. METHODS: Three tag genetic variants (rs2004640, rs2070197 and rs10954213), representative of 3 different haplotype blocks within IRF5, were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls by TaqMan assays. RESULTS: No significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each IRF5 polymorphism was evaluated independently. Likewise, no significant differences between patients with IgAV and healthy controls were found when we assessed the three IRF5 polymorphisms combined, conforming haplotypes. In addition, there were no significant differences in genotype, allele and haplotype frequencies of IRF5 when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IRF5 on the pathogenesis of IgAV.

Influence of IL17A gene on the pathogenesis of immunoglobulin-A vasculitis.

OBJECTIVES: Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. Interleukin (IL)17A is described as a genetic risk locus for some autoimmune diseases, such as giant cell arteritis and spondyloarthritis. Accordingly, we aimed to determine the potential influence of IL17A on the pathogenesis of IgAV. METHODS: Five IL17A tag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), which cover the major variability of this gene, were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls using TaqMan probes. RESULTS: No statistically significant differences between patients with IgAV and healthy controls were observed when each IL17A genetic variant was analysed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the five IL17A polymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies of IL17A when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IL17A on the pathogenesis of IgAV.

Quality standard for the management of patients with psoriatic arthritis: QUANTUM Project. / Norma de calidad para el manejo del paciente con artritis psoriásica: proyecto QUANTUM.

OBJECTIVE: To generate a quality standard for the management of patients with psoriatic arthritis (PsA). METHODS: We employed qualitative methodology that included: 1) Two focus groups (one with patients with PsA and another with non-rheumatologist specialists involved in the care of PsA patients); 2) A narrative literature review of published documents related to the quality of care in PsA; 3) A nominal group meeting in which 15 expert rheumatologists generated and reached a consensus on a series of quality criteria, as well as formulas or quantifiable objective measures to evaluate them; 4) The Delphi method to establish the feasibility, priority and agreement with the quality criteria; 5) A final generation of standards of care and their attributes. A descriptive analysis of the results was carried out. RESULTS: A total of 59 standards of care was generated, 18 of mandatory compliance, grouped into 4 blocks according to specific objectives: 1) early diagnosis (n=6); 2) optimizing the management of the disease (n=26); 3) multidisciplinary collaboration (n=9); 4) monitoring improvement (n=18). To assess compliance with these standards of care, in many cases, the medical records will be reviewed. Other sources will be the records of the service and hospital and bibliographic databases. Regarding the level of compliance, for some of the standards of care this is yes/no; for others, compliance ranges from 50% to 100% and, in this range, in many cases, compliance was 80%. CONCLUSIONS: This set of standards of care should help improve quality of care in PsA patients.

Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología / Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): aims and methodology

OBJETIVOS: Describir la metodología del Registro Español de Artritis Psoriásica de reciente comienzo de la Sociedad Española de Reumatología (REAPSER), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronósticos de la evolución clínica y radiográfica en una cohorte de pacientes que padecen artritis psoriásica (APs) diagnosticada con menos de 2 años de evolución. MATERIAL Y MÉTODO: Estudio observacional, prospectivo (2 años de seguimiento; periodicidad anual de las visitas), multicéntrico. La intención en la visita basal fue reflejar la situación del paciente antes de que la evolución de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatología. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatólogo. El tamaño muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemográficos; de situación laboral; historia familiar; antecedentes personales y comorbilidad; antropométricos; estilo de vida; uso de los servicios de salud; situación clínica al diagnóstico de APs; afectación articular y dolor espinal; dolor y valoración global de la enfermedad; entesitis, dactilitis y uveítis; afectación cutánea y ungueal; situación funcional y calidad de vida; evaluación radiográfica; determinaciones analíticas; tratamiento; brotes en esqueleto axial y periférico. CONCLUSIONES: El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolución de la enfermedad se viese modificada por la prescripción de FAME en los servicios de reumatología. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis

Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): Aims and methodology. / Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología.

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis.

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.