Alejandro Escudero

First signs and symptoms of spondyloarthritis—data from an inception cohort with a disease course of two years or less (REGISPONSER-Early)

Objective. To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA. Methods. A total of 150 SpA patients were selected from 2367 listed in REGISPONSER (Registro Español de Espondiloartritis de la Sociedad Española de Reumatología). The inclusion criterion was a disease course of ⩽2 yrs from the onset of symptoms or the appearance of the first sign of disease. Results. Forty-six patients had AS, 51 psoriatic SpA (Ps-SpA), 43 uSpA, 5 ReA, 4 IBD arthropathy and 1 JCA. The mean age at onset of symptoms and at diagnosis was higher in Ps-SpA group (48.1 ± 13.6 and 48.5 ± 13.6 yrs) than in AS group (38.1 ± 12.8 and 38.9 ± 12.7 yrs) and uSpA group (36.3 ± 11.5 and 36.9 ± 11.4 yrs). The most frequent signs or symptoms were back pain: 72% AS group and 56% uSpA group. Lower limb arthritis was the first symptom in 57% Ps-SpA patients, 35% uSpA patients and 20% AS patients; upper limb arthritis was the first symptom in 53% Ps-SpA group and <16% of the remainder. Compared with longer duration disease, at onset, AS patients report upper limb arthritis more frequently and uSpA patients report more of enthesitis. Early radiological sacroiliitis was observed in all AS patients, of whom 54% had Grade II, 39% had Grade III and 7% had Grade IV. Conclusions. In our population, the first manifestations of SpA were low back pain and SI syndrome in AS and uSpA patients and peripheral arthritis in the Ps-SpA group. We can find early SI joint affectation in AS patients.

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

Objective— Previous studies have suggested a relationship between anticyclic citrullinated protein (CCP) levels and development of cardiovascular disease in rheumatoid arthritis (RA). However, a limited number of studies have demonstrated an involvement of anti-CCPs in those processes. This study was aimed to define the specific role of these auto-antibodies in the pro-oxidative, inflammatory, and proatherogenic profile observed in leukocytes from RA patients. Approach and Results— Seventy-five RA patients and 31 healthy donors were enrolled. Carotid intima media thickness was evaluated as atherosclerosis marker. Several procoagulant and inflammatory factors, leukocyte activation, and oxidative stress markers were analyzed in plasma and leukocyte subsets. Anti-CCPs were purified from plasma of RA patients, and in vitro treatment of healthy leukocytes was conducted. High titers of anti-CCPs were associated to altered expression of prothrombotic and inflammatory markers, high oxidative stress, and pathological carotid intima media thickness in RA patients. Notably, gene expression analysis showed that lymphocytes were major players in altered inflammatory profile, monocytes were responsible for the protrombotic and atherogenic status, and neutrophils mainly displayed a pro-oxidative feature. In vitro treatment with purified anti-CCPs fully recapitulated that pathogenic profile, promoting the activation of leukocytes. Conclusions— Anti-CCPs are key players in the inflammatory and proatherogenic status of RA patients. The effects are specific of the immune cell targeted, promoting overexpression of thrombotic, inflammatory, and pro-oxidative markers in monocytes; pro-oxidative status in neutrophils; and proinflammatory profile in lymphocytes. Targeting these autoantibodies would be an excellent strategy to prevent the development of cardiovascular disease in RA.

Assessment of the efficacy of joint lavage versus joint lavage plus corticoids in patients with osteoarthritis of the knee

SUMMARY Purpose: Joint lavage (JL), involves the passage of cold sterile 0.9% saline through the knee joint in order to have the fluid reach the inside of the joint capsule. This technique was evaluated as a local treatment for osteoarthritis (OA) of the knee alone (JL) and in combination with intra-articular infiltration with glucocorticoids (JLC). Patients and methods: An overall 299 knees belonging to 205 patients (22% males, 78% females) with a mean age of 67 ± 8u2009years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were randomised in the ratio of 1:4 into two therapeutic groups, namely: JL (n = 62) and JLC (n = 237). All patients received joint lavage on day 0; in those of the JLC group, joint lavage was followed by infiltration of 40u2009mg of triamcinolone acetonide. The efficacy of both treatments was assessed by recording the corresponding values for the following variables: pain strength as measured by a visual analogy scale (VAS), effusion, crepitation, restricted motion, spontaneous pain, pain on pressure, pain on passive motion and pain on active motion; all of these were recorded at the onset of the study, and after 1 and 3u2009months. Results: There were no significant differences in the values of the variables at the different follow-up times. Also, pain severity was similar in both treatment groups. Thus, VAS for pain was 7.3 ± 0.3 for the JL group and 7.1 ± 0.2 for the JLC group at the onset, and decreased to 3.0 ± 0.3 in the former and 2.8 ± 0.2 in the latter after 1u2009month; the decrease was statistically significant in both cases. After 3u2009months, the JL and JLC groups had a VAS of 3.5 ± 0.3 and 3.8 ± 0.2, respectively. Conclusions: The results of this work suggest the absence of significant differences between the two treatments, such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management of osteoarthritis of the knee.

First acute gout attacks commonly precede features of the metabolic syndrome.

Objective:To determine in gout patients, the temporal relationship between the first gout attack and the diagnosis of metabolic syndrome (MS), its components and complications. Subjects and Methods:We included consecutive gout patients attending 2 Rheumatology Departments from Spain (Hospital Universitario Reina Sofía) and México (Hospital General de México). Variables included demographic, clinical, and biochemical data: Hypertension, hypertriglyceridemia, low high density lipoproteins (HDL), obesity, hyperglycemia or diabetes, MS (Adult Treatment Pane III criteria), ischemic heart disease (IHD), and chronic renal failure (CRF). Age and date (year) of the diagnosis of first acute gout attack and associated diseases were obtained. Results:Four hundred seven patients were included (96% men); mean age at onset, mean age at inclusion, and mean duration of the disease were 39.7 ± 13, 52.5 ± 13, and 13.7 ± 9.9 years, respectively. In 90%, the first attack of gout preceded the diagnosis of features of MS, MS itself or its complications (CRF and IHD), 9.8% had previous diagnosis of at least 1 associated disease. At the time of the inclusion (mean, 13.7 years after the first attack), 93% had at least 1 associated disease. The most common were hypertriglyceridemia, 63%; obesity, 54%; hypertension, 45.6%; MS, 40%; hyperglycemia, 37%; low HDL, 17%; diabetes, 15%; CRF, 17%; and IHD, 6.6%. Although patients from the 2 Rheumatology Departments had several demographic and clinical differences, in both groups most of the patients (70% Hospital Universitario Reina Sofía and 95% Hospital General de México) had no diagnosis of any associated disease previous to first bouts and at inclusion most of them had the diagnosis of at least 1 associated disease. Conclusions:First attacks of gout may precede the diagnosis of metabolic abnormalities and associated diseases, and provids a unique opportunity to diagnose, prevent, and/or retard long-term complications in these patients.

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6

OBJECTIVESnTo perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease.nnnMETHODSnLinkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs.nnnRESULTSnFine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans.nnnCONCLUSIONSnThese results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.

Standards of care for patients with spondyloarthritis

To define and give priory to standards of care in patients with spondyloarthritis (SpA). A systematic literature review on SpA standards of care and a specific search in relevant and related sources was performed. An expert panel was established who developed the standards of care and graded their priority (high, mild, low, or no priority) following qualitative methodology and Delphi process. An electronic survey was sent to a representative sample of 167 rheumatologists all around the country, who also gave priority to the standards of care (same scale). A descriptive analysis is presented. The systematic literature review retrieved no article specifically related to SpA patients. A total of 38 standards of care were obtained—12 related to structure, 20 to process, and 6 to result. Access to care, treatment, and safety standards of care were given a high priority by most of rheumatologists. Standards not directly connected to daily practice were not given such priority, as standards which included a time framework. The standards generated for the performance evaluation (including patient and professionals satisfaction) were not considered especially important in general. This set of standards of care should help improve the quality of care in SpA patients.

Validation of a new objective index to measure spinal mobility: the University of Cordoba Ankylosing Spondylitis Metrology Index (UCOASMI).

AbstractSpinal mobility measures are subject to high variability and subjectivity. Automated motion capture allows an objective and quantitative measure of mobility with high levels of precision.n To validate the University of Cordoba Ankylosing Spondylitis Metrology Index (UCOASMI), an index measure of spinal mobility, based on automated motion capture, validation studies included the following: (1) validity, tested by correlation—Pearson’s r—between the UCOASMI and the mobility index Bath Ankylosing Spondylitis Metrology Index (BASMI), and a measure of structural damage, the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); (2) reliability, with internal consistency tested by Cronbach’s alpha, test–retest by intraclass correlation coefficient (ICC) after 2xa0weeks, and error measurement, by variation coefficient (VC) and smallest detectable difference (SDD); and (3) responsiveness, by effect size (ES) in a clinical trial of anti-TNF. Patients for the different studies all had ankylosing spondylitis. Validity studies show correlation between the BASMI (rxa0=xa00.881) and the mSASSS (rxa0=xa00.780). Reliability studies show an internal consistency of Cronbach’s αxa0=xa00.894, intra-observer ICCxa0=xa00.996, test–retest ICCxa0=xa00.996, and a measurement error of VCxa0=xa02.80xa0% and SDDxa0=xa00.25 points. Responsiveness showed an ES after 24xa0weeks of treatment of 0.48. In all studies, the UCOASMI’s performance was better than that of the BASMI. The UCOASMI is a validated index to measure spinal mobility with better metric properties than previous indices.

Identification of patients at risk of non-adherence to oral antirheumatic drugs in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an ARCO sub-study

The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18xa0years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky–Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6xa0years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48xa0years; 37.5%) was double that recorded in patients aged >48xa0years (pxa0=xa00.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (pxa0=xa00.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky–Green assessment tools (kappa coefficientxa0=xa00.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.

Usefulness of a centralized system of data collection for the development of an international multicentre registry of spondyloarthritis

Objective. To present the usefulness of a centralized system of data collection for the development of an international multicentre registry of SpA. Method. The originality of this registry consists in the creation of a virtual network of researchers in a computerized Internet database. From its conception, the registry was meant to be a dynamic acquiring system. Results. REGISPONSER has two developing phases (Conception and Universalization) and gathers several evolving secondary projects (REGISPONSER-EARLY, REGISPONSER-AS, ESPERANZA and RESPONDIA). Each sub-project answered the necessity of having more specific and complete data of the patients even from the onset of the disease so, in the end, obtaining a well-defined picture of SpAs spectrum in the Spanish population. Conclusion. REGISPONSER is the first dynamic SpA database composed of cohorts with a significant number of patients distributed by specific diagnosis, which provides basic specific information of the sub-cohorts useful for patients’ evaluation in rheumatology ambulatory consulting.

Use of prognostic factors of rheumatoid arthritis in clinical practice and perception of their predictive capacity before and after exposure to evidence

The aim of the study is to benchmark the use and attributed importance of well-established prognostic factors in rheumatoid arthritis (RA) in daily clinical practice, and to contrast the use of factors with their ability to predict outcome. Medline was searched (inception-Sep. 2016) for systematic reviews on factors predicting death, disability, structural damage or remission in RA. All factors identified were compiled in a matrix of factorsxa0×xa0outcomes, and scoping reviews for each cell were then performed. A survey to 42 rheumatologists randomly selected explored the use of the list of prognostic factors and inquired about the perceived strength of association with poor prognosis. In a second round, participants were exposed to evidence from the matrix and to responses from other participants. Change on perceived strength of association was evaluated. Rheumatologists report using prognostic factors in clinical practice on a daily basis. Very young onset, joint counts at diagnosis, rheumatoid factor, ACPA, and radiographic erosions are used frequently and correctly recognized as strong predictors. Comorbidities and other associated problems, such as obesity, low bone mineral density, cardiovascular disease, or extra-articular manifestations, are perceived as moderately associated to prognosis but, nevertheless, rheumatologists also use them profusely. Genetic and other biomarkers and osteitis by magnetic resonance are less accessible in daily practice and they obtained better results on second round (probably after knowing the strength of association with prognosis). Rheumatologists use widely most prognostic factors with a strong predictive value. However, factors with low evidence of prognostic value are also used and some factors are not used despite good evidence.