Beneficial effect of temporary methotrexate interruption on B and T cell responses upon SARS-CoV-2 vaccination in patients with rheumatoid arthritis or psoriatic arthritis.

B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.

Volumetric BMD by 3D-DXA and Trabecular Bone Score in Adults With Down Syndrome.

Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm3 vs 206.9 ± 46.7 mg/cm3, p = 0.007, and 250.5 ± 70.1 mg/cm3 vs 275.7 ± 66.2 mg/cm3, p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects.

Clinically significant renal involvement in primary Sjögren's syndrome is associated with important morbidity: data from the Spanish Sjögrenser cohort.

OBJECTIVES: To investigate the prevalence, associated factors, and effects of primary overt renal disease on morbidity in patients with primary Sjögren's syndrome (pSS). METHODS: All patients in the Sjögrenser (registry of adult pSS patients of the Spanish Society of Rheumatology) cohort were retrospectively investigated for the presence of clinically significant renal involvement directly related to pSS activity. RESULTS: Of the 437 patients investigated, 39 (9%) presented overt renal involvement during follow-up. Severe renal disease necessitating kidney biopsy was relatively rare (2%). Renal involvement may complicate pSS at any time during the disease course and is associated with severe disease (indicated by higher scores of involvement, activity, and damage), systemic multiorgan involvement, and a higher frequency of lymphoma. Multivariate analysis showed that older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.07), higher European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores (OR 1.1, CI 1.03-1.18), serum anti-La/SSB positivity (OR 6.65, CI 1.41-31.372), and non-vasculitic cutaneous involvement (OR 5.47, 1.03-29.02) were independently associated with this complication. Chronic renal failure developed in 23 of 39 patients (59%); only 1 of them progressed to end-stage renal disease necessitating renal replacement therapy. Patients with overt renal disease showed higher Sjögren's syndrome disease damage index scores, higher rates of hospitalisation due to disease activity and higher rates of clinically relevant comorbidities. CONCLUSIONS: Overt renal involvement in pSS is not uncommon. Although it usually shows a favourable prognosis, is associated with significant morbidity.

Reproducibility of Metacarpal Bone Mineral Density Measurements Obtained by Dual-Energy X-Ray Absorptiometry in Healthy Volunteers and Patients With Early Arthritis.

Reduction in cortical bone mineral density at diaphysis of metacarpal bones of the hand, evaluated by dual X-ray radiogrammetry, has a bad prognostic value in patients with early arthritis. Nevertheless, this technique is hardly accessible in clinical practice. By contrast, evaluation of cortical bone mineral density at that location has not been previously assessed by conventional dual X-ray absorptiometry. The aim of this study is to evaluate the reproducibility of bone mineral density measurements at diaphysis of metacarpal bones using conventional dual X-ray densitometry in a population of healthy volunteers and patients with early arthritis. Nondominant hand dual X-ray densitometry was performed at three consecutive times with complete hand replacement in 27 subjects: 10 early arthritis and 17 healthy volunteers. Three different evaluators analyzed the 3 measurements of second to fourth metacarpal bones. To assess the reproducibility and accuracy of the measurements, intra- and interobserver agreement degrees, intra- and interclass correlation coefficients, smallest difference detectable assessment, and Bland Altman graphs were calculated. The coefficients of variation obtained for the different metacarpal evaluations were 2.25%, 2.91%, 2.85%, and 2.07% for metacarpal-2, metacarpal-3, metacarpal-4, and mean metacarpal-second to fourth, respectively, with a smallest difference detectable of 0.028, 0.034, 0.028, and 0.03 g/cm2, respectively. The mean intra- and interobserver correlation coefficients between of metacarpal second to fourth were 0.990 (95% confidence interval [CI]: 0.982-0.995) and 0.995 (95% CI: 0.991-0.997), respectively. As expected, women had lower bone mineral density at metacarpal bones, especially after menopause. The results obtained in this study show an excellent reproducibility of bone mineral density measurements at diaphysis of metacarpal bones of the hand, measured by conventional dual X-ray densitometry, in a mixed population of healthy subjects and patients with early arthritis. This is of great interest for longitudinal studies in patients with early arthritis.

Hyperlipoproteinaemia(a) in patients with spondyloarthritis: results of the Cardiovascular in Rheumatology (CARMA) project.

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.

Sustained remission after long-term biological therapy in patients with large vessel vasculitis: an analysis of ten cases / Remisión sostenida tras terapia biológica en pacientes con vasculitis de grandes vasos: análisis de 10 casos

Objectives. To describe the results obtained in clinical practice with the use of biological therapy (BT) in patients diagnosed with Takayasu arteritis (TA) and giant cell arteritis (GCA). Methods. Retrospective single center study of TA/GCA patients who received BT (infliximab [IFX], etanercept [ETN] and tocilizumab [TCZ]). In TA, active disease was defined according to a previous National Institutes of Health study. In GCA, active disease was defined with a modified criteria and clinical manifestations secondary to temporal artery involvement or polymyalgia rheumatica symptoms. Clinical data and outcomes are reported using descriptive statistics. Results. Five patients with TA and 5 with GCA were included. The main reason for starting BT was lack of response to prior therapy and/or ≥2 relapses during GC tapering. Five patients started IFX, four TCZ and 1 ETN. Remission was observed before 6 months in all cases. Only one patient had a relapse during long-term follow-up and the overall GC daily dose was reduced by 70%. Two AEs were considered attributable to IFX and one to TCZ. Conclusion. A favorable and sustained response to BT was observed in our patients with TA and GCA. Thus, BT might be considered as an alternative in patients with large vessel arteritis refractory to conventional treatment or with GC related comorbidities (AU)

Objetivos. Describir los resultados obtenidos en la práctica clínica diaria con el uso de la terapia biológica (TB) en pacientes con diagnóstico de arteritis de Takayasu (AT) y arteritis de células gigantes (ACG). Métodos. Estudio retrospectivo monocéntrico de pacientes con AT/ACG que recibieron TB (infliximab, etanercept y tocilizumab). En AT, la enfermedad activa se definió de acuerdo a un estudio previo del National Institutes of Health. En ACG, la enfermedad activa se definió con dichos criterios modificados y manifestaciones clínicas secundarias a afectación de la arteria temporal o síntomas de polimialgia reumática. Los datos y los desenlaces clínicos se muestran mediante estadística descriptiva. Resultados. Se incluyeron 5 pacientes con AT y 5 con ACG. La razón principal para el inicio de la TB fue la falta de respuesta al tratamiento previo y/o ≥2 recaídas durante la terapia con corticoides. Cinco pacientes comenzaron infliximab, 4 tocilizumab y uno etanercept. La remisión se observó antes de los 6 meses en todos los casos. Solo un paciente tuvo una recaída durante el seguimiento a largo plazo. La dosis diaria de corticoides se redujo globalmente en un 70%. Dos acontecimientos adversos se consideraron atribuibles a infliximab y uno a tocilizumab. Conclusión. Se observó una respuesta favorable y sostenida a la TB en nuestros pacientes con AT y ACG. Por lo tanto, la TB puede ser considerada una alternativa en pacientes refractarios al tratamiento convencional o con comorbilidades asociadas a los corticoides (AU)

Anti-citrullinated protein antibodies are associated with decreased bone mineral density: baseline data from a register of early arthritis patients.

Since the previous studies showed that anti-citrullinated protein antibodies (ACPA) can induce osteoclasts differentiation and activation, even before arthritis onset, the aim of our study was to determine whether ACPA-positivity is associated with lower bone mineral density (BMD) at baseline visit of a register of early arthritis (EA) patients. The study population comprised 578 patients (80% females) from our EA clinic with a median disease duration, 5.1 months (p25-p75: 6-8); median age, 53.6 years (41.9-66.1), 38% ACPA-positive, and 55% fulfilling 2010 criteria for rheumatoid arthritis. BMD was measured using dual X-ray absorptiometry at lumbar spine, hip, and metacarpophalangeal (MCP) joints of the non-dominant hand to evaluate both systemic and juxta-articular bone mass. ACPA titers were determined through enzyme immunoassay. The effect of ACPA on BMD was analyzed using multivariable analysis based on generalized linear models adjusted for various confounders. ACPA-positive patients showed lower bone mass at lumbar spine and hip, but no differences were observed at MCP joints compared to ACPA-negative patients. However, ACPA-positive patients displayed higher disease activity and disability than ACPA-negative patients. After adjustment for gender, age, body mass index, and other bone-related variables, the presence of ACPA remained significantly associated with lower BMD at the lumbar spine, femoral neck, and hip but not at MCP joints. Disease activity was not associated with baseline bone mass. Our data reinforce the previous preclinical findings suggesting that the systemic bone loss detected at the initial phases of early ACPA-positive arthritis is independent of inflammatory status and, therefore, could be mediated by ACPA.

Sustained remission after long-term biological therapy in patients with large vessel vasculitis: an analysis of ten cases.

OBJECTIVES: To describe the results obtained in clinical practice with the use of biological therapy (BT) in patients diagnosed with Takayasu arteritis (TA) and giant cell arteritis (GCA). METHODS: Retrospective single center study of TA/GCA patients who received BT (infliximab [IFX], etanercept [ETN] and tocilizumab [TCZ]). In TA, active disease was defined according to a previous National Institutes of Health study. In GCA, active disease was defined with a modified criteria and clinical manifestations secondary to temporal artery involvement or polymyalgia rheumatica symptoms. Clinical data and outcomes are reported using descriptive statistics. RESULTS: Five patients with TA and 5 with GCA were included. The main reason for starting BT was lack of response to prior therapy and/or ≥2 relapses during GC tapering. Five patients started IFX, four TCZ and 1 ETN. Remission was observed before 6 months in all cases. Only one patient had a relapse during long-term follow-up and the overall GC daily dose was reduced by 70%. Two AEs were considered attributable to IFX and one to TCZ. CONCLUSION: A favorable and sustained response to BT was observed in our patients with TA and GCA. Thus, BT might be considered as an alternative in patients with large vessel arteritis refractory to conventional treatment or with GC related comorbidities.