The impact of psoriasis on the clinical characteristics, disease burden and treatment patterns of peripheral spondyloarthritis.

OBJECTIVES: To evaluate the clinical characteristics, disease burden, and treatment patterns of peripheral spondyloarthritis (pSpA) patients with and without psoriasis using data from the ASAS-perSpA study. METHODS: We included 433 patients who had a diagnosis of pSpA according to the rheumatologist's diagnosis from the ASAS-PerSpA study. The presence of a personal history of psoriasis was defined as the presence of signs of psoriasis at physical examination or the presence of psoriatic nail dystrophy, including onycholysis, pitting and hyperkeratosis, or a history of psoriasis diagnosed by a physician. Clinical characteristics, patient-reported outcomes and treatment pattern were compared between subgroups with and without psoriasis. RESULTS: A total of 83 patients (19.2%) had a personal history of psoriasis. Patients with psoriasis were older (48.4 vs 43.2 years) and had a longer diagnostic delay (7.4 vs 3.5 years), a higher frequency of dactylitis (36.1 vs 20.0%) and enthesitis (65.1 vs 55.4%) than patients without psoriasis. A longer diagnostic delay (odds ratio [OR] = 1.06 [95% CI 1.01, 1.11]), lower odds for HLA-B27 positivity (OR = 0.31 [95% CI 0.15, 0.65]) and higher odds for enthesitis (OR = 2.39 [95% CI 1.16, 4.93]) were associated with the presence of psoriasis in a multivariable regression analysis. While patient-reported outcomes were comparable between groups, a higher use of biologic DMARDs was observed in patients with vs without psoriasis. CONCLUSION: The presence of psoriasis has an impact on clinical characteristics of pSpA. pSpA patients without psoriasis were less frequently treated with biologic DMARDs despite similar disease burden as compared with patients with psoriasis.

Age at onset in axial spondyloarthritis around the world: data from the Assessment in SpondyloArthritis international Society Peripheral Involvement in Spondyloarthritis study.

OBJECTIVE: Age at onset is useful in identifying chronic back patients at an increased risk of axial SpA (axSpA). However, the majority of data on which the criterion of age at onset <45 years is based originates from Europe. Therefore it is unknown if this criterion applies in other parts of the world. We aimed to assess the age at onset of axSpA and its relationship with HLA-B27 and gender across the world. METHODS: Analyses were applied to patients from 24 countries across the world with an axSpA diagnosis and known age at onset of axial complaints. Cumulative probability plots were used to display the cumulative distribution of age at onset of axial symptoms. Linear regression models were built to assess the effect of HLA-B27 and gender on age at onset of axial symptoms. RESULTS: Of 2579 axSpA patients, 92% had an age at onset of axial symptoms <45 years, with only small variations across the geographical regions [Asia, n = 574 (94%); Europe and North America, n = 988 (92%); Latin America, n = 246 (89%); Middle East and North Africa, n = 771 (91%)]. Age at onset of axial symptoms was consistently lower in HLA-B27-positive patients {median 25 years [interquartile range (IQR) 19-32] vs 31 [IQR 22-39]} and male patients [median 25 years (IQR 19-33) vs 28 (IQR 21-37)], but in multivariable models an additional statistically significant effect of male gender independent of HLA-B27 was only found in Asia. CONCLUSION: Around the world, the great majority of axSpA patients had an age at onset of axial disease of <45 years, with HLA-B27 and male gender associated with earlier disease onset.

Assessment of Subclinical Psychotic Symptoms in Patients with Rheumatoid Arthritis and Spondyloarthritis.

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms.

Which factors explain the patient global assessment in patients with ankylosing spondylitis? A hierarchical cluster analysis on REGISPONSER-AS.

OBJECTIVES: To determine groups of factors (clusters) potentially associated with the patient global assessment (measured with the Bath Ankylosing Spondylitis Patient Global Score (BAS-G)), and to quantify the contribution of each cluster to the patient's well-being. METHODS: This was a cross-sectional study in patients with a diagnosis of ankylosing spondylitis (AS) from the national, multicentre Spanish REGISPONSER-AS registry. A hierarchical cluster analysis was conducted to group the potential factors (sociodemographic, socioeconomic, patient-reported outcomes, physical exploration variables and depression) associated with the BAS-G. The contribution of each cluster to the variability of the BAS-G was evaluated using a multivariate linear regression model and the determination coefficient (R2) for each cluster. RESULTS: A total of 681 patients with complete data were included. Three clusters of variables potentially associated with the BAS-G were found: cluster 1 contained the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), depression, sex (female) and university studies; cluster 2 included the Graffar scale, age and body mass index; and cluster 3 contained the Bath Ankylosing Spondylitis Functional Index (BASFI), the individual items of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain during the last week, nocturnal pain and the number of swollen joints. A total of 6.8% of the variability of the BAS-G was explained by cluster 1, 0.5% was explained by cluster 2, and 60.8% was explained by cluster 3. CONCLUSION: The BAS-G is mostly explained by pain and function, while demographic and socioeconomic factors are weakly associated with the BAS-G. Depression also has a weak effect on this score.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

ASAS Health Index in patients with spondyloarthritis and its association with disease activity and disease burden including fibromyalgia.

OBJECTIVES: To evaluate the association of the Assessment of Spondyloarthritis international Society Health Index (ASAS-HI) with disease activity and disease burden in patients with spondyloarthritis (SpA). METHODS: Observational, cross-sectional and single-centre study from the Córdoba AxSpA Task force, Registry and Outcomes (CASTRO). Scores related to disease activity (BASDAI and ASDAS), functionality (BASFI), structural damage, mobility, health and the presence of concomitant fibromyalgia (FM) were obtained from all patients. ASAS-HI score was considered the main outcome. Pearson's r statistic, Student's t test, and univariate and multivariate linear regressions were performed to assess the association between the ASAS-HI score and the studied covariates. RESULTS: A total of 126 SpA patients were included. The mean ASAS-HI score was 4.6±3.9, showing a "strong" positive linear correlation (r>0.60) with the BASDAI and BASFI and a "moderate" positive linear correlation (r=0.40 to 0.60) with the global VAS and ASDAS. Patients with FM showed a significantly higher ASAS-HI score than patients without FM (9.5±3.2 vs. 3.7±3.4, respectively, p<0.01). Multiple linear regression showed that 57.4% of the ASAS-HI variability (R2=0.574) was explained by the presence of concomitant FM (ß=2.23, 95% CI 0.73 to 3.80, p=0.004), higher scores on the BASDAI (ß=0.62, 95% CI 0.25 to 0.97, p=0.001) and BASFI (ß=0.57, 95% CI 0.26 to 0.88, p=0.001). CONCLUSIONS: The impairment of health in patients with SpA was mainly associated with high disease activity, worsening functionality and with the presence of a possible concomitant FM. Therefore, in patients with high ASAS-HI scores we must evaluate the presence of concomitant FM.

Axial and peripheral spondyloarthritis: does psoriasis influence the clinical expression and disease burden? Data from REGISPONSER registry.

OBJECTIVE: To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). METHODS: Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. RESULTS: A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27+ [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27+ (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. CONCLUSION: These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

Assessment of the relationship between estimated cardiovascular risk and structural damage in patients with axial spondyloarthritis.

AIMS: To evaluate the association of estimated cardiovascular (CV) risk and subclinical atherosclerosis with radiographic structural damage in patients with axial spondyloarthritis (axSpA). METHODS: Cross-sectional study including 114 patients axSpA from the SpA registry of Córdoba (CASTRO) and 132 age- and sex-matched healthy controls (HCs). Disease activity and the presence of traditional CV risk factors were recorded. The presence of atherosclerotic plaques and carotid intima media thickness (cIMT) were evaluated through carotid ultrasound and the SCORE index was calculated. Radiographic damage was measured though modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The association between mSASSS and SCORE was tested using generalized linear models (GLM), and an age-adjusted cluster analysis was performed to identify different phenotypes dependent on the subclinical CV risk. RESULTS: Increased traditional CV risk factors, SCORE, and the presence of carotid plaques were found in axSpA patients compared with HCs. The presence of atherosclerotic plaques and SCORE were associated with radiographic structural damage. The GLM showed that the total mSASSS was associated independently with the SCORE [ß coefficient 0.24; 95% confidence interval (CI) 0.10-0.38] adjusted for disease duration, age, tobacco, C-reactive protein, and non-steroidal anti-inflammatory drugs (NSAID) intake. Hard cluster analysis identified two phenotypes of patients. Patients from cluster 1, characterized by the presence of plaques and increased cIMT, had a higher prevalence of CV risk factors and SCORE, and more structural damage than cluster two patients. CONCLUSION: Radiographic structural damage is associated closely with increased estimated CV risk: higher SCORE levels in axSpA patients were found to be associated independently with mSASSS after adjusting for age, disease duration, CRP, tobacco and NSAID intake.

Clinical manifestations, disease activity and disease burden of radiographic versus non-radiographic axial spondyloarthritis over 5 years of follow-up in the DESIR cohort.

OBJECTIVES: To compare the clinical manifestations, disease activity and disease burden between patients with radiographic (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) over a 5-year follow-up period in the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. METHODS: Patients from the DESIR cohort who had X-ray images of the sacroiliac joints available at baseline and did not leave the study during the 5-year follow-up period because of a diagnosis other than axSpA were included. A unilateral rating of 'obvious sacroiliitis' by the local reader was considered sufficient for classification as r-axSpA. The incidence of first episodes of peripheral and extra-rheumatic manifestations was compared between the two groups using the incidence rate ratio and Cox regressions adjusted for sex, age and tumour necrosis factor blocker (TNFb) intake. Mean values of patient-reported outcomes (PROs) and days of sick leave over 5 years of follow-up were compared using mixed models adjusted for sex, age, TNFb intake and baseline values. RESULTS: In total, 669 patients were included, of whom 185 (27.7%) and 484 (72.3%) were classified as r-axSpA and nr-axSpA, respectively. At baseline, the r-axSpA patients showed a significantly higher prevalence of males. After adjusting for age, sex and TNFb intake, Cox regressions for peripheral and extra-rheumatic manifestations did not show any significant differences between groups. Mixed models also showed similar mean levels in PROs and days of sick leave between groups over time. CONCLUSION: The incidence of peripheral and extra-rheumatic manifestations as well as the disease burden over time remained similar between r-axSpA and nr-axSpA groups after adjusting for intermediate variables. TRIAL REGISTRATION NUMBER: NCT01648907.

Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis.

Objectives: To compare the clinical characteristics, burden of disease (eg, disease activity, function, quality of life), treatment modalities and treatment effect in patients with radiographic and non-radiographic axial Spondyloarthritis (r-axSpA and nr-axSpA). Methods: A systematic literature review (2009-2018) was performed using the participants, intervention, comparator and outcomes methodology. Studies reporting outcomes (clinical presentation, burden of disease, treatment modalities and treatment effect) of both r-axSpA and nr-axSpA were included. A pooled analysis was performed (standardised means difference and relative risk for continuous and binary variables, respectively) and random or fixed effects methods were used depending on the heterogeneity of the studies. Results: 60 studies out of 787 references were included. Pooled analysis showed that, compared with patients with nr-axSpA, patients with r-axSpA were more frequently men (69.6% vs 53.6%), smokers (37.7% vs 31.1%) and had higher mean disease duration (8.6 vs 5.0 years) and longer time to diagnosis (6.1 vs 4.2 years). Peripheral manifestations were more prevalent in nr-axSpA, while uveitis and structural damage on MRI of the sacroiliac joints were more prevalent in r-axSpA. C-reactive protein and the Bath Ankylosing Spondylitis Mobility Index were higher in r-axSpA, while Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life were similar in both groups. No significant differences were found with regard to treatment effect. Conclusions: Patients with r-axSpA and nr-axSpA share a similar clinical presentation except for peripheral involvement, which is more prevalent among nr-axSpA. Except for a more impaired mobility in r-axSpA, both groups showed a comparable burden of disease, treatment modalities and treatment effect.

Assessment of the adherence to disease-modifying drugs in patients with chronic inflammatory rheumatic diseases: Results of a survey of 1594 patients.

OBJECTIVES: a) to describe the self-reported adherence to disease modifying drugs (DMARDs) (methotrexate and biological DMARDs) among patients with chronic inflammatory rheumatic diseases (CIRDs); b) to assess factors associated with non-adherence. METHODS: An observational, cross-sectional, nationwide study was conducted through the use of an electronic survey, which was released via patient organizations in France to rheumatic patients. The main outcome was the rate of non-adherence to DMARDs, which was evaluated with the following question "Have you ever tried to stop or space out your treatment in contrast to what was planned with your doctor?" A positive answer was considered "low adherent". Sociodemographic variables, type of CIRD and treatment information were also collected. Factors associated with low adherence to methotrexate and bDMARDs were explored by univariate and multivariate logistic regressions. RESULTS: Among the 1594 participants who completed the survey, 795 (49.9%) were receiving methotrexate and 709 (44.5%) bDMARDs. A total of 159 (20.0%) were identified as low adherents to methotrexate, and being a woman was independently associated with low adherence (OR 1.90 [95% CI 1.07 - 3.36)] to this drug. Regarding bDMARDs, 177 (25.0%) were identified as low adherent, and the factors independently associated with low adherence were being employed (OR 1.47 [95% CI 1.04 - 2.09]) and no concomitant use of methotrexate (OR 0.51 [95% CI 0.36 - 0.73]). CONCLUSIONS: This study suggests that more than 20% of CIRDs patients are low adherent to their DMARDs, and this is more frequent when bDMARDs are administered as a monotherapy.

Cardiovascular risk factors in patients with spondyloarthritis from Northern European and Mediterranean countries: An ancillary study of the ASAS-COMOSPA project.

OBJECTIVES: The objectives of this study were: (1) to compare the prevalence of cardiovascular disease and cardiovascular risk factors among different phenotypes of spondyloarthritis (SpA); (2) to assess the differences in cardiovascular disease and cardiovascular risk factors between two geographical areas, i.e. Northern Europe vs. Mediterranean region; (3) to identify potential predictive factors for high Framingham Risk Score regarding disease features in SpA and geographical area. METHODS: Ancillary analysis of the international, multicentric, observational, cross-sectional ASAS-COMOSPA study. Cardiovascular disease and cardiovascular risk factors were compared depending on SpA phenotype and geographical regions. Potential factors associated with higher cardiovascular risk (i.e. Framingham Risk Score) were determined by a multiple logistic regression. RESULTS: The most frequent cardiovascular risk factor and cardiovascular disease were smoking (31.2%) and ischemic heart disease (3.2%), respectively. Regarding SpA phenotype, axial SpA patients showed significantly lower prevalence (P<0.05) of hypertension (19.2% vs. 33.8% vs. 26.6% for axial, peripheral and mixed phenotypes, respectively), type 2 diabetes mellitus (4.3% vs. 8.5% vs. 7.4%), dyslipidemia (13.9% vs. 28.4% vs. 15.2%) and ischemic heart disease (2.4% vs. 7.0% vs. 3.2%). Regarding geographical area, a higher frequency of hypertension (34.7% vs. 19.4%,), dyslipidemia (19.3% vs. 14.4%), obesity (29.3% vs. 20.7%) and ischemic heart disease (6.2% vs. 1.8%) was observed for Northern Europe vs. Mediterranean Region, respectively. CONCLUSIONS: Our results suggest that SpA phenotype and geographical area are associated with the prevalence of cardiovascular risk factors and the cardiovascular risk itself, observed in patients in the ASAS-COMOSPA cohort.

Assessment of Fatigue in Spondyloarthritis and Its Association with Disease Activity.

OBJECTIVE: To evaluate fatigue in patients with spondyloarthritis (SpA) and to define its association with disease-related factors and patients' features. METHODS: A cross-sectional multicenter study which includes 2251 patients with SpA selected from the national Spondyloarthropathies Registry (the Spanish Society of Rheumatology; REGISPONSER) Spanish cohort. The primary outcome was the assessment of fatigue performed with the first item of the Bath Ankylosing Spondyloarthritis Disease Activity Index followed by the study of its relation with different factors organized into 4 groups: sociodemographics, emotional, disease-related, and disease activity. Univariate logistic regressions, multivariate logistic regression, and multiple linear regressions were performed to relate fatigue with the studied covariates. RESULTS: Mean fatigue score in all patients with SpA was 4.3 ± 2.9, with statistically significant differences between different SpA types. In univariate logistic regressions, significant differences were seen for many variables included in the 4 groups. Multivariate logistic regression showed that high fatigue score was related with sex (female), emotional component, the Ankylosing Spondylitis Quality of Life score, stiffness, and high levels of 2 visual analog scale items (vertebral pain in the last week and patient's global assessment of disease activity). The multivariate linear regression showed that fatigue was mainly explained by disease-related factors and disease activity (54.1%), but sex and emotional status may also be involved in 13.5% of the variance. CONCLUSION: Fatigue is associated with disease-related factors and mostly with SpA activity. However, the emotional component and sex may contribute to the onset of fatigue.