Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

OBJECTIVES: To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. METHODS: Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. RESULTS: We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. CONCLUSION: In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation.

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS: Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS: After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION: bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.

Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis.

OBJECTIVES: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. METHODS: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. RESULTS: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. CONCLUSION: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.

The prolactin receptor is expressed in rheumatoid arthritis and psoriatic arthritis synovial tissue and contributes to macrophage activation.

OBJECTIVES: Prolactin (PRL) is a lactation-inducing hormone with immunomodulatory properties and is found at elevated levels in the serum of patients with RA and other rheumatic diseases. The PRL receptor (PRLR) has been shown to be expressed by macrophages in atherosclerotic plaques. The aim of this study was to examine PRLR expression by synovial macrophages and its role in the regulation of macrophage activation. METHODS: Serum monomeric 23 kDa PRL levels were measured in 119 RA patients using a fluoroimmunometric assay. PRLR expression was assessed in synovial tissue of 91 RA, 15 PsA and 8 OA patients by immunohistochemistry and digital image analysis. Double IF was used to identify PRLR-expressing cells. The effects of PRL on monocyte-derived macrophage gene expression were examined by quantitative real-time PCR and ELISA. RESULTS: Serum PRL levels were similar in female and male RA patients. Median (interquartile range) PRLR expression was significantly higher (P < 0.05) in RA and PsA synovial tissue compared with OA. PRLR colocalized with synovial CD68+ macrophages and von Willebrand factor+ endothelial cells. In vitro, PRLR was prominently expressed in IFN-γ-and IL-10-polarized macrophages compared with other polarizing conditions. PRL by itself had negligible effects on macrophage gene expression, but cooperated with CD40L and TNF to increase expression of pro-inflammatory genes including IL-6, IL-8 and IL-12ß. CONCLUSIONS: Synovial PRLR expression is enhanced in patients with inflammatory arthritis compared with OA, and PRL cooperates with other pro-inflammatory stimuli to activate macrophages. These results identify PRL and PRLR as potential new therapeutic targets in inflammatory arthritis.

DAS28, CDAI and SDAI cut-offs do not translate the same information: results from the Rheumatic Diseases Portuguese Register Reuma.pt.

OBJECTIVES: . The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients. Cut-off values were defined to classify the states of RA disease activity: remission, low, moderate and high. The aim of this work was to assess disease activity states classified by DAS28, CDAI and SDAI and to analyse their agreement in the Rheumatic Diseases Portuguese Register Reuma.pt. METHODS: . A total of 2795 patients and 14 440 visits were selected from Reuma.pt for analysis. Pearson's correlation coefficients (PCCs) were calculated for the three indices. McNemar's chi-squared tests, PCCs and kappa statistics were performed to analyse and compare the distribution of visits among all disease activity states and indices. RESULTS: A strong correlation was found between the three indices throughout the 14 440 visits: r = 0.874 for DAS28/CDAI, r = 0.877 for DAS28/SDAI and r = 0.984 for CDAI/SDAI (all PCCs with P < 0.0001). However, when categorization in the different disease activity states was analysed, McNemar's chi-squared tests and PCCs revealed significant disagreement between the cut-offs of the three indices. CONCLUSION: DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA.

Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals.

OBJECTIVE: The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals. METHODS: A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs). RESULTS: ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10(-3)] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10(-2)), rs10050860 (OR = 0.7, P = 2.3 × 10(-2)), rs2287987 (OR = 0.6, P = 1.3 × 10(-2)). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10(-3)) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10(-2)). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10(-2), OR = 1.3). No associations were observed in the TNFSF15 region. CONCLUSION: The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis.

CASE REPORT: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. DISCUSSION: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.

Hepatitis B vaccination associated with low response in patients with rheumatic diseases treated with biologics.

BACKGROUND: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs. OBJECTIVES: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs. METHODS: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded. RESULTS: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified. CONCLUSIONS: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Smoking is a predictor of worse trabecular mechanical performance in hip fragility fracture patients.

Clinical risk factors (CRFs) are established predictors of fracture events. However, the influence of individual CRFs on trabecular mechanical fragility is still a subject of debate. In this study, we aimed to assess differences, adjusted for CRFs, between bone macrostructural parameters measured in ex-vivo specimens from hip fragility fracture patients and osteoarthritis patients, and to determine whether individual CRFs could predict trabecular bone mechanical behavior in hip fragility fractures. Additionally, we also looked for associations between the 10-year risk of major and hip fracture calculated by FRAX and trabecular bone mechanical performance. In this case-control study, a group of fragility fracture patients were compared with a group of osteoarthritis patients, both having undergone hip replacement surgery. A clinical protocol was applied in order to collect CRFs [body mass index (BMI), prior fragility fracture, parental history of hip fracture, long-term use of oral glucocorticoids, rheumatoid arthritis, current smoking, alcohol consumption, age and gender]. The 10-year probability of fracture was calculated. Serum bone turnover markers were determined and dual X-ray absorptiometry performed. Femoral head diameter was evaluated and trabecular bone cylinders were drilled for mechanical testing to determine bone strength, stiffness and toughness. We evaluated 40 hip fragility fracture and 52 osteoarthritis patients. Trabecular bone stiffness was significantly lower (p = 0.042) in hip fragility fracture patients when compared to osteoarthritic individuals, adjusted for age, gender and BMI. No other macrostructural parameter was statistically different between the groups. In hip fragility fracture patients, smoking habits (ß = -0.403; p = 0.018) and female gender (ß = -0.416; p = 0.008) were independently associated with lower stiffness. In addition, smoking was also independently associated with worse trabecular strength (ß = -0.323; p = 0.045), and toughness (ß = -0.403; p = 0.018). In these patients, the 10-year risk of major (r = -0.550; p = 0.012) and hip fracture (r = -0.513; p = 0.021) calculated using only CRFs was strongly correlated with femoral neck bone mineral density but not with mechanical performance. Our data showed that among fragility fracture patients active smoking is a predictor of worse intrinsic trabecular mechanical performance, and female gender is also independently associated with lower stiffness. In this population, the 10-year risk of fracture using CRFs with different weights only reflects bone mass loss but not trabecular mechanical properties.

Histopathology of Psoriatic Arthritis Synovium-A Narrative Review.

Psoriatic arthritis (PsA) is a phenotypically heterogeneous chronic inflammatory disease associated to type I major histocompatibility complex alleles whose complex pathogenesis is still not completely understood. The psoriatic synovium shares general features of chronic inflammation with rheumatoid arthritis (RA) and other arthritis, such as hyperplasia of the intimal lining layer, sublining influx of inflammatory cells and neoangiogenesis, but recognizing disease-specific histopathologic findings may help in diagnosis and definition of therapeutic targets. Available literature reports conflicting data regarding the extension of lining hyperplasia, that does not allow depiction from RA. Sublining inflammatory cells consist of T and B cells and macrophages, plasma cells, mast cells and follicular dendritic cells, with a higher amount of overall T, mast cell and IL-17 producing CD8+ T lymphocytes and lower proportion of plasma cells when compared to the rheumatoid synovium. The amount of synovium IL17+ CD8+ T cells correlates positively to measures of disease activity. Lymphoid follicles with characteristics of germinal centers have been identified, similar to the ones described in RA. Neoangiogenesis is more prominent in PsA but can also be an outstanding feature in some RA samples, and different molecules involved in the process appear to have different influence in each disease. IL-17 and IL-22 expression in the synovium does not allow depiction between diseases. Among other cytokines and molecules likely implicated in disease physiopathology, only IL-35 is demonstrated to be reduced in PsA when compared to RA.

Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis - data from the COMOSPA and COMORA studies.

OBJECTIVES: To assess the hierarchy of outcomes contributing to health-related quality of life (HRQoL) in spondyloarthritis (SpA) and rheumatoid arthritis (RA). METHODS: Data from the international cross-sectional COMOSPA and COMORA studies were used. HRQoL was assessed using the EuroQOL 5-dimension 3-level (EQ-5D-3 L). First, multivariable linear regression models were used to identify associations between EQ-5D-3 L (dependent variable) and several demographic and clinical variables (independent variables). Second, a decision tree was built using Chi-square Automatic Interaction Detector, a method of unbiased hierarchical multivariable analysis (dependent variable: EQ-5D-3 L). RESULTS: In total, 3984 patients with SpA and 3920 patients with RA were included. In SpA, HRQoL was associated with BASFI (adjusted B=-0.006; 95%CI=-0.007 to -0.005), ASDAS (-0.052; -0.071 to -0.033), work productivity loss score (-0.002; -0.003 to -0.002), NSAID treatment (-0.052; -0.083 to -0.020), bDMARD treatment (-0.051; -0.082 to -0.021), university education (-0.051; -0.075 to -0.027) and radiographic sacroiliitis (0.035; 0.004 to 0.030). In RA, HRQoL was associated with modified Health Assessment Questionnaire (MHAQ) (-0.220, -0.253 to -0.188), DAS28-CRP-3v (-0.027, -0.036 to -0.018), work productivity loss score (-0.003, -0.003 to -0.002), presence of erosions (-0.042, -0.065 to -0.020), alcohol consumption ≥3 units/day (0.012, 0.001 to 0.024)) and csDMARD treatment (0.034, 0.001 to 0.066). The decision tree revealed BASFI and MHAQ as first variables with the most discriminative power on EQ-5D-3 L, followed by work productivity loss and disease activity, in both SpA and RA cohorts. CONCLUSION: In SpA and RA, physical function is the main contributor to HRQoL measured by EQ-5D-3 L, followed by disease activity and work productivity loss.

Sex differences in axial spondyloarthritis: data from a Portuguese spondyloarthritis cohort.

BACKGROUND: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male's disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy. OBJECTIVE: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging. METHODS: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA registered in the electronic Rheumatic Diseases Portuguese Register (Reuma.pt) were included in this multicentric cross-sectional study. Sociodemographic data, clinical features and imaging were collected from the first record in Reuma.pt. These variables were compared between sexes using Mann-Whitney test and Chi-Square test. Variables with a significant association with variable sex were considered in the multiple variable analysis to adjust the sex effect on the outcome variables. Statistical analysis was performed with R version 4.0.2 and p <0.05 was considered statistically significant. RESULTS: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had an earlier disease onset (25.1 vs 28.4, p <0.001), were younger at diagnosis (26.9 vs 30.4, p<0.001) and were more frequently smokers (32.1% vs 15.7%, p <0.001). Comparing to women, men had worse Bath Ankylosing Spondylitis Metrological Index scores (4.0 vs 3.4, p<0.001), higher levels of C-Reactive Protein (10.5 vs 6.9 mg/L, p <0.001) and were more often Human Leukocyte Antigen-B27 positive (67.8% vs 54%, p <0.001). In contrast, women more frequently had inflammatory bowel disease (8.8% vs 4.9%, p =0.004), higher levels of erythrocyte sedimentation rate (25.0 vs 21.0mm/h, p=0.003) and worse patient-related outcomes- Bath Ankylosing Spondylitis Disease Activity Index (5.7 vs 4.5, p<0.001), Patient Global Assessment (60.0 vs 50.0, p <0.001) and fatigue (6.2 vs 5.0, p <0.001). DISCUSSION: In this large multicentric study from a Portuguese axSpA cohort, we confirmed sex differences in patients with axSpA. This work brings awareness to these differences, resulting in less underdiagnosis and misdiagnosis, optimizing treatment strategies, and improving outcomes in axSpA.

Evaluating antirheumatic treatments using synovial biopsy: a recommendation for standardisation to be used in clinical trials.

Inflammation of synovium is one of the hallmarks of rheumatoid arthritis (RA). Analysis of synovial tissue has increased our understanding of RA pathogenesis, aided in identifying potential therapeutic targets and has been used in the response and mechanistic evaluation of antirheumatic treatments. In addition, studies are ongoing, aimed at the identification of diagnostic and prognostic biomarkers in the synovium. This paper outlines the currently used procedures for sampling and processing of synovial tissue, and presents a standardised recommendation to support multicentre translational research.