Patients With Psoriatic Arthritis-Related Enthesitis and Persistence on Tofacitinib Under Real-World Conditions.

OBJECTIVE: Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. METHODS: This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. RESULTS: Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. CONCLUSION: In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.

Influence of the HLA-Cw6 Allele and IFIH1/MDA5 Gene Variants on the Cardiometabolic Risk Profile of Patients with Psoriatic Disease.

BACKGROUND: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. METHODS: A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk were determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. RESULTS: The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 was protective (OR: 0.65). HLA-Cw6 carriers showed a lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p < 0.001) and diabetes (OR: 0.36, p < 0.001), but these findings were no longer apparent upon adjusting the regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. CONCLUSIONS: The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

Managing psoriatic arthritis in different clinical scenarios.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, immune-mediated disease characterized by synovio-entheseal inflammation. It is estimated to affect around 30% of patients with psoriasis and significantly reduces patients' physical function and quality of life. There is a growing number of treatment options for PsA, but due to the heterogeneous clinical features of the disease and prevalence of comorbidities, managing PsA can be challenging. AREAS COVERED: In this article, we review current understanding of the disease and available pharmacological options. Based on published treatment guidelines, emerging evidence and clinical experience, we provide our expert opinion on treatment strategies, taking into consideration the predominant disease domain and the presence of comorbidities, which can impact treatment decisions and clinical outcomes. EXPERT OPINION: Biological and targeted synthetic disease-modifying agents are dramatically improving the lives of patients with PsA. Biosimilar TNF inhibitors offer a particularly versatile and cost-effective option, whilst newer biologics and targeted synthetic molecules that can be used to treat most domains of psoriatic disease are an attractive alternative to TNF inhibitors. Despite a lack of consensus on treatment sequencing and tapering, it is important that PsA patients, especially those with comorbidities, are looked after by a multidisciplinary team to optimize their care.

Osteomalacia in Adults: A Practical Insight for Clinicians.

The term osteomalacia (OM) refers to a series of processes characterized by altered mineralization of the skeleton, which can be caused by various disorders of mineral metabolism. OM can be genetically determined or occur due to acquired disorders, among which the nutritional origin is particularly relevant, due to its wide epidemiological extension and its nature as a preventable disease. Among the hereditary diseases associated with OM, the most relevant is X-linked hypophosphatemia (XLH), which manifests in childhood, although its consequences persist into adulthood where it can acquire specific clinical characteristics, and, although rare, there are XLH cases that reach the third or fourth decade of life without a diagnosis. Some forms of OM present very subtle initial manifestations which cause both considerable diagnosis and treatment delay. On occasions, the presence of osteopenia and fragility fractures leads to an erroneous diagnosis of osteoporosis, which may imply the prescription of antiresorptive drugs (i.e., bisphosphonates or denosumab) with catastrophic consequences for OM bone. On the other hand, some radiological features of OM can be confused with those of axial spondyloarthritis and lead to erroneous diagnoses. The current prevalence of OM is not known and is very likely that its incidence is much higher than previously thought. Moreover, OM explains part of the therapeutic failures that occur in patients diagnosed with other bone diseases. Therefore, it is essential that clinicians who treat adult skeletal diseases take into account the considerations provided in this practical review when focusing on the diagnosis and treatment of their patients with bone diseases.

Are Patients with Axial Spondyloarthritis Who Were Breastfed Protected against the Development of Severe Disease?

BACKGROUND AND AIMS: Breastfeeding is recognized as one of the most influential drivers of the gut microbiome. In turn, alterations in the gut microbiome may play a role in the development and severity of spondyloarthritis (SpA). We aimed to analyze different disease outcomes in patients with axial SpA (axSpA) based on the history of breastfeeding. PATIENTS AND METHODS: A random sample was selected from a large database of axSpA patients. Patients were divided based on history of breastfeeding and several disease outcomes were compared. Both groups were also compared based on disease severity. Adjusted linear and logistic regression statistical methods were used. RESULTS: The study included 105 patients (46 women and 59 men), and the median age was 45 years (IQR: 16-72), and the mean age at diagnosis was 34.3 ± 10.9 years. Sixty-one patients (58.1%) were breastfed, with a median duration of 4 (IQR: 1-24) months. After the fully adjusted model, BASDAI [-1.13 (95%CI: -2.04, -0.23), p = 0.015] and ASDAS [-0.38 (95%CI: -0.72, -0.04), p = 0.030] scores were significantly lower in breastfed patients. Forty-two percent had severe disease. In the adjusted logistic model for age, sex, disease duration, family history, HLA-B27, biologic therapy, smoking, and obesity, breastfeeding had a protective effect against the development of severe disease (OR 0.22, 95%CI: 0.08-0.57, p = 0.003). The selected sample size was sufficient to detect this difference with a statistical power of 87% and a confidence level of 95%. CONCLUSION: Breastfeeding might exert a protective effect against severe disease in patients with axSpA. These data need further confirmation.

Treatment Retention and Safety of Ixekizumab in Psoriatic Arthritis: A Real Life Single-Center Experience.

Background and objectives: Information on the performance of ixekizumab (IXE) in patients with psoriatic arthritis (PsA) in clinical practice is scarce. We aimed to analyze the retention rate and safety of IXE in patients with PsA in routine clinical practice. Methods: A retrospective longitudinal observational single-center study of all patients with PsA who had received at least one dose of IXE. Adverse events (AEs) and drug retention rate were the main study focus. Survival was analyzed using Kaplan−Meier curves and predictive factors using multivariate Cox regression analysis. The hazard ratio (HR) was used as a measure of the association. Results: Seventy-two patients were included (52 women and 20 men). Median disease duration was 5 years (IQR 3−9). More than 90% received ≥2 biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) prior to IXE. Ixekizumab showed a 1-year retention rate of 65% and a 2-year retention rate of 57%. Regarding discontinuation due to AEs, 0.18 AEs per person-year were identified. The number of previous biologics did not influence drug survival but prior use of methotrexate (HR 2.31 (95% CI 1.05−5.10), p < 0.05) and depression (HR 2.40 (95% CI 1.07−5.41), p < 0.05) increased the risk of IXE discontinuation. Conclusions: Ixekizumab showed a good retention rate in a PsA population mostly refractory to biologic and targeted synthetic DMARDs. Drug survival was consistently good regardless of age, gender, metabolic comorbidities, smoking status, or prior number of biologic therapies. This information may be of interest to better position this drug in the PsA treatment algorithms.

Differentiated Effect of Smoking on Disease Activity and Quality of Life among Different Spondyloarthritis Phenotypes.

BACKGROUND AND AIMS: The effect of smoking on disease activity and quality of life (QoL) in spondyloarthritis (SpA) is far from clear. We aimed to evaluate the relationship between smoking and these outcomes in patients with axial SpA (axSpA) and psoriatic arthritis (PsA). PATIENTS AND METHODS: This cross-sectional observational multicenter study included 242 patients with axSpA and 90 with PsA. The association between conventional cardiovascular risk factors and disease activity as well as QoL, in both SpA phenotypes was evaluated. For this, univariate and multivariate regression analyses were performed, as well as confirmatory meta-analyses. RESULTS: Regardless of age, sex, or disease duration, patients with axSpA showed significantly less association with obesity (OR 0.50 (0.26-0.96), p = 0.03) and hypertension (OR 0.33 (0.18-0.62), p = 0.0005). However, axSpA was significantly associated with smoking (OR 2.62 (1.36-5.04), p = 0.004). Patients with axSpA were more likely to be in a category of high disease activity compared with PsA (OR 2.86, p = 0.0006). Regardless of sex, age, disease duration, and education level, smoking was significantly associated with higher disease activity in axSpA (OR 1.88, p = 0.027). A fixed-effects model meta-analysis (OR 1.70, p = 0.038) confirmed the association between tobacco and disease activity. No relationship was found between smoking (or other cardiometabolic risk factors) and structural damage or worse QoL in either disease. CONCLUSIONS: Although the cardiometabolic risk profile is clearly different between both SpA phenotypes, the only clear link between these factors and increased disease activity was observed between smoking and axSpA. Our findings need further confirmation.

Performance of the ASAS Health Index for the Evaluation of Spondyloarthritis in Daily Practice.

OBJECTIVE: The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a tool designed to assess disease impact in spondyloarthritis (SpA), but its clinical performance is barely known. We aimed to test the clinimetric properties of ASAS HI in a real clinical setting. METHODS: This cross-sectional study included 111 consecutive patients with SpA. The measurement properties of ASAS HI were tested against conventional assessment measures. Convergent validity was assessed by Spearman rho correlations, while discriminative validity was analyzed through receiver-operating characteristic (ROC) curves. A multivariate regression analysis was designed to identify ASAS HI items associated with active disease. RESULTS: The average ASAS HI was 5.4 ± 3.8 (interquartile range 3-8). ASAS HI showed high convergent validity against other SpA measures (rho ≥ 0.70, p < 0.0005). The optimal criteria for detecting high/very high disease activity Ankylosing Spondylitis Disease Activity Score (ASDAS) categories was an ASAS HI score > 6, area under the ROC curve 0.86 (95% CI 0.78-0.92), positive likelihood ratio 7.3 (95% CI 3.1-17.1), p < 0.0001. The ASAS HI items significantly associated with Bath Ankylosing Spondylitis Disease Activity Index active disease were "I often get frustrated" (OR 9.2, 95% CI 1.2-69.4, p = 0.032), and "I sleep badly at night" (OR 7.7, 95% CI 1.4-41.6, p = 0.018). As for ASDAS, it was "pain sometimes disrupts my normal activities" (OR 8.7, 95% CI 1.7-45.2, p = 0.010). CONCLUSION: The ASAS HI is a useful and simple instrument for its application in daily practice. Given its good clinimetric properties, it could be used as an additional instrument to evaluate SpA.

Enthesitis and joint erosions are disease traits associated with cardiovascular risk in psoriatic arthritis.

AIM: To analyze the prevalence of subclinical atherosclerosis (SA), as well as the factors associated with it, in psoriatic arthritis (PsA). METHODS: This cross-sectional observational study included 140 consecutive patients with PsA. Systematic COronary Risk Evaluation (SCORE) risk charts and carotid ultrasound (CU) were used to estimate cardiovascular risk (CVR). The presence of plaque and/or a carotid intima-media thickness (cIMT) > 0.9 mm defined SA. Disease features associated with SA were analyzed. RESULTS: The prevalence of SA in this study was 25%. According to the SCORE charts, 42.8%, 35.7%, and 21.5%, had low, moderate, and high-very high CVR, respectively. The best criterion to define a high CVR (by SCORE plus carotid plaques) corresponded to a cIMT > 0.63 mm (area under the ROC curve 0.75 (0.66-0.82), p < 0.0001). Patients in minimal disease activity (MDA) showed less SA (cIMT > 0.9 mm, 6.2% vs. 30.2% in non-MDA, p < 0.05, and carotid plaques in 23.7% vs. 32.6% in non-MDA). Disease factors associated with SA were age (OR 1.08 (1.03-1.13), p < 0.001), smoking (OR 4.26 (1.44-12.65), p = 0.01), enthesitis (OR 3.76 (1.36-10.40), p = 0.01), and erosive disease (OR 5.23 (1.33-20.50), p = 0.02). CONCLUSIONS: Subclinical atherosclerosis was associated with both classic CVR factors as well as others more linked to the inflammatory nature of this disease. Patients reaching the MDA showed less SA. Cardiovascular risk should be closely monitored in PsA patients who develop enthesitis and/or structural damage. Key Points • Subclinical atherosclerosis is relatively common in psoriatic arthritis. • Patients reaching the minimal disease activity response show less subclinical atherosclerosis. • Patients with enthesitis and/or structural damage are a high-risk population for subclinical atherosclerosis.

Disease Activity in Psoriatic Arthritis Index and Psoriatic Arthritis Impact of Disease Questionnaire: correlation and sensitivity to change in a real clinical setting.

OBJECTIVES: The performance of many outcome measures for psoriatic arthritis (PsA) is almost unknown in real clinical practice. Our objective was to study the correlation and sensitivity to change of the Disease Activity in Psoriatic Arthritis (DAPSA) index and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire in a real practice setting. METHODS: This was a prospective, open, non-controlled study that included 60 consecutive patients with PsA treated with ustekinumab. Most had been previously treated with one or more biologic therapeutic agents. The correlation (Spearman's rho coefficient) and the sensitivity to change [Standardized Mean Response (SMR)] of DAPSA and PsAID were studied. Effect size values of 0.20, 0.50 and 0.80 corresponded to low, moderate and high sensitivity to change, respectively. RESULTS: More than 70% of patients achieved therapeutic goals (21.7% were in remission and 50% in low disease activity according to DAPSA categories). Two out of three patients reached an acceptable symptomatic state (PsAID <4). The correlation between final values of both instruments was substantial (Spearman's rho: 0.62, p<0.0001). The SMR for the PsAID was 1.08 (0.95-1.21) and for DAPSA was 1.5 (1.37-1.63), both values corresponding to instruments with a high sensitivity to change (>0.80). The best PsAID cut-off value for identifying DAPSA remission was 3.32 with an area under the ROC curve of 0.82. CONCLUSIONS: DAPSA and PsAID seem to be useful instruments for a more comprehensive assessment of PsA in daily practice. Our results can help to disseminate the use of these instruments in the clinical practice of many rheumatologists.

Analysis by Age Group of Disease Outcomes in Patients with Psoriatic Arthritis: A Cross-Sectional Multicentre Study.

OBJECTIVES: Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups. METHODS: This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: < 40, 40‒49, 50‒65 and > 65 years. Physical functioning, disease activity, remission rates and disease impact were compared. RESULTS: Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40-49 years, 26.4% (n = 60) were 50-65 years and 33.0% (n = 75) were patients > 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p < 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged < 40 years, 13.1% of patients aged 40-49 years and 26.7% of patients aged 50-65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged < 40 years, more patients > 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p < 0.05). CONCLUSIONS: Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.

Obesity in psoriatic arthritis: Comparative prevalence and associated factors.

Obesity is a common cardiovascular risk factor in psoriatic disease. Although the prevalence of obesity is high, the factors associated with it in patients with psoriatic arthritis (PsA) are poorly understood. We aimed to analyze the frequency and obesity-associated factors in a cohort of PsA.This retrospective cross-sectional study included 290 consecutive patients with PsA according to CASPAR criteria. Three-hundred ten psoriatic patients without arthritis and 600 outpatients without inflammatory conditions were used as comparison populations. The factors associated with obesity were analyzed first using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach.This series included 159 men (54.8%) and 131 women (45.2%), with an average age of 54 ±â€Š12 years. Obesity was more common both in psoriasis (36.5% vs 22%, OR 2.1 [95%CI: 1.5-2.8), P < .01]) and PsA (27.6% vs 22%, OR 1.4 [95%CI: 1.0-1.9], P < .05) than in the non-inflammatory population. Obesity was more frequent in psoriasis (36.5%) than in PsA (27.6%), OR 1.5 95% CI: 1.1 to 2.1, P < .05. After correcting for age, sex, disease duration, and other confounders, independent associations with obesity (P < .05) were: PsA family history (OR 3.6, 95%CI: 1.1-12.4), evolution as axial disease (OR 4.4, 95%CI: 1.0-15.4), and dyslipidemia (OR 3.5, 95%CI: 1.5-8.6).Obesity is common in psoriatic disease, but much more frequent among patients with cutaneous than joint disease. Patients who present with spondylitis during evolution are more prone to this comorbidity, and therefore, should be closely monitored to correct this eventuality in a timely manner.

Hypertension is associated with increased age at the onset of psoriasis and a higher body mass index in psoriatic disease.

BACKGROUND AND AIMS: High blood pressure (HBP) is a common comorbidity in psoriatic disease. Some studies indicate a higher prevalence of HBP among arthritis patients, in relation to psoriasis alone, within the psoriatic spectrum. Our objective was to study the prevalence of HBP in both types of patients as well as to analyse the factors associated with it. METHODS: A cross-sectional observational study of 600 patients with psoriatic disease attended in a multidisciplinary clinic of a reference centre. We first analysed the frequency of this comorbidity and then the factors associated with it using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach. RESULTS: A total of 144 patients were hypertensive (24%). Of patients with arthritis, 86/290 (29.7%) had HBP, compared with 58/310 (18.7%) with psoriasis (OR 1.7 95%, CI 1.25-2.50, p = 0.003). Hypertension was independently associated with higher age at onset of psoriasis (OR 1.04, 95%CI 1.03-1.06, p < 0.001) and a higher body mass index (OR 1.13, 95%CI, 1.06-1.22, p < 0.001). CONCLUSIONS: HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. Patients with a higher body mass index and those with later-onset psoriasis are more prone to this comorbidity. KEY POINTS: • The factors of psoriatic disease associated with HBP are little known. • HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. • In patients with psoriatic disease, for each point of increase in the body mass index, the risk of HBP increases by 13%. • For each year of onset of psoriasis above 40 years, the risk of HBP increases by 4%.

Polyarticular evolution and late-onset psoriasis may be associated with cardiovascular disease in psoriatic arthritis.

BACKGROUND AND AIMS: Patients with psoriatic arthritis (PsA) have high prevalence of cardiovascular risk factors (CVRF), and they also show higher rates of cardiovascular disease (CVD). We aimed to corroborate these findings and identify factors associated with these events in our clinical setting. METHODS: This cross-sectional study included 340 consecutive patients seen in a tertiary care hospital. The prevalence of CVRF was compared to that of 600 outpatients without inflammatory conditions. To analyze CVD-associated factors, odds ratio (OR) values were calculated by conditional logistic regression analysis. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. RESULTS: Patients with psoriatic arthritis had higher frequencies of hypertension (36% vs 23%, OR 2.4, 95%CI: 1.6-2.7, P < 0.0001), diabetes (13.8% vs 5%, OR 2.8, 95%CI: 1.7-4.3, P < 0.0001), obesity (35% vs 22%, OR 2.1, 95%CI: 1.5-2.8, P < 0.0001) and tobacco use (26% vs 21%, OR 1.4, 95%CI: 1.0-1.8, P < 0.05). More PsA patients had CVD compared to non-inflammatory patients (9.4% vs 5.8%, OR 1.68, 95%CI: 1.02-2.76, P < 0.05). Independent CVD-associated factors were: an age of onset of psoriasis >40 years (OR 3.4, 95%CI: 1.1-10.0, P < 0.05), a high number of swollen joints during evolution (OR 2.9, 95%CI: 1.1-8.0, P < 0.05), hypertension (OR 5.3, 95%CI: 1.6-17.6, P < 0.01) and dyslipidemia (OR 2.6, 95%CI: 1.0-7.2, P < 0.05). CONCLUSIONS: Cardiovascular risk should be carefully evaluated in patients with PsA whose disease presents a high inflammatory burden and in those with late-onset psoriasis.

Prevalence and type II diabetes-associated factors in psoriatic arthritis.

Diabetes is a common cardiovascular risk factor in psoriatic arthritis (PsA). Although the prevalence of diabetes is high, the factors associated with it in PsA are poorly understood. We aimed to analyse the prevalence of type II diabetes and diabetes-associated factors in a hospital-based population with PsA. This cross-sectional study included 340 consecutive patients attended in a tertiary care hospital. The prevalence of diabetes was compared to that of 600 outpatients without inflammatory conditions. To analyse diabetes-associated factors, odds ratio (OR) values were calculated by conditional logistic regression analysis. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. Diabetes was more prevalent among PsA patients (13.8 vs. 5%, OR 2.8, 95% CI: 1.7-4.3, p < 0.0001). Diabetes-associated factors in the univariate analysis (p < 0.05) were the following: an age of onset of psoriasis > 40 years, an age of onset of arthritis > 40 years, a low educational level, family history of psoriasis, pustular psoriasis, high number of swollen joints during follow-up, hypertension, dyslipidemia, obesity, and cardiovascular events. After controlling for several confounders, diabetes was significantly associated with late-onset psoriasis (OR 8.2, 95% CI: 1.9-12.4, p = 0.002) and hypertension (OR 7.5, 95% CI: 1.5-13.3, p = 0.008). Diabetes risk should be carefully evaluated in patients with PsA whose psoriasis begins after 40 years.