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.

Searching for a Novel HLA-Cw6-Linked Cardiometabolic Endotype in Psoriatic Disease.

BACKGROUND/OBJECTIVES: In recent years, a possible connection between HLA-Cw6 and a distinctive cardiometabolic (CM) profile in patients with psoriatic disease (PsD) has been proposed, although there is still little support for this. Our aim was to further investigate this possible association by studying a large population of PsD patients. METHODS: For this study, three different cohorts of patients with PsD were analyzed: two with a majority of cutaneous psoriasis, pooled n: 600, and a third with only psoriatic arthritis-PsA-cases, n: 340. Potential relationships between HLA-Cw6 and the different CM risk factors (hypertension, diabetes, obesity, dyslipidemia) were analyzed using univariate and multivariate regression models, while the final net effect was assessed using fixed- or random-effects meta-analyses, as appropriate. RESULTS: In the PsA cohort, no association was detected between HLA-Cw6 carriership and any of the CM comorbidity factors. In psoriasis cohorts, after correcting for age, sex, disease duration, and arthritis, HLA-Cw6 carriers had a reduced diabetes risk (OR 0.49, 95%CI: 0.26-0.91, p = 0.026). This latter effect was confirmed by a fixed-effects meta-analysis of the included cohorts (pooled OR: 0.50, 95%CI: 0.27-0.90). CONCLUSIONS: This work demonstrates a potential protective effect of the HLA-Cw6 allele on the risk of diabetes in PsD. Our findings together with those of others seem to confirm the existence of a novel HLA-Cw6-linked cardiometabolic endotype in this disease.

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.

Altered sleep in axial spondyloarthritis and psoriatic arthritis: Post hoc comparative study based on a sleep-specific question from the ASAS health index.

BACKGROUND AND AIMS: Sleep problems are common in spondyloarthritis (SpA), but the factors associated with them are only partially known. In this study, responses to item #16 from the Assessment of SpondyloArthritis international Society-Health Index (ASAS HI) that explores the sleep category according to the International Classification of Functioning, Disability and Health (ICF) were compared between psoriatic arthritis (PsA) and axial SpA (axSpA). METHODS: Post hoc analysis of a multicentre cross-sectional study included a total of 201 consecutive patients. The prevalence, correlations, and disease factors associated with a positive response to item #16 were analyzed in both SpA populations. RESULTS: Forty-eight/111 (43.2%) patients with axSpA and 42/90 (46.7%) with PsA reported sleep problems. There was a moderate-high correlation between item #16 and the ASAS HI sum score in both populations (r≥.59). In axSpA, poor sleep was associated with disease activity (OR 8.45, p<.001), biological therapy use (OR .24, p<.05) and CRP levels (OR .16, p<.05). In PsA, disturbed sleep was independently associated with disease activity showing a dose-response effect (OR 1.16, p<.001). Taking both populations together, disease severity (OR 6.33, p<.001) and axSpA (OR .50, p<.05) were independently associated with a positive response to item #16. Correlations between the different components of the ASAS HI and item #16 were markedly different in both populations. CONCLUSIONS: A positive response to item #16 was common in both SpA phenotypes. However, the link between inflammatory burden and disturbed sleep was higher in axSpA than in PsA.

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.

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.

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.

Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA-C∗06 Status.

The human leukocyte antigen-C∗06 (HLA-C∗06, formerly HLA-Cw6) is the main genetic biomarker in psoriatic disease. It has been related to several phenotypic traits in psoriatic disease, but its role in relation to cardiometabolic comorbidities is unknown at present. Here, we analyze the potential connections between this biomarker and the cardiometabolic profile of these patients. We carried out a cross-sectional observational study including 400 patients recruited at a single university hospital. Clinical and classical cardiometabolic factors were compared between HLA-C∗06-positive and HLA-C∗06-negative individuals (OR with 95% CI). Multivariate regression analyses were carried out to check for disease traits associated with different cardiometabolic risk factors. The study population included 215 men (53.8%) and 185 women (46.2%), mean age of 46 ± 15 years, and an average disease evolution of 17 ± 12.6 years. Ninety-three (23.3%) patients met CASPAR criteria for psoriatic arthritis. HLA-C∗06 carriers (n: 160, 40%) showed an earlier age at disease onset, psoriasis family history, and more severe skin disease (type I disease). After correcting for age, sex, and disease duration, they also showed less hypertension (13.8% vs. 24.2%, OR 0.7 (95% CI: 0.42-0.78), p = 0.025), lower waist circumference (94.4 ± 13.7 vs. 98.3 ± 13.8 cm), and lower BMI (27 ± 4.4 vs. 28.1 ± 4.8, p < 0.05). We confirmed the well-known association between HLA-C∗06 and type I psoriatic disease. As a novel finding, patients carrying HLA-C∗06 showed a better cardiometabolic profile. In any case, these findings need further confirmation.

Altered sleep in axial spondyloarthritis and psoriatic arthritis: Post hoc comparative study based on a sleep-specific question from the ASAS health index / Alteración del sueño en la espondiloartritis axial y la artritis psoriásica: análisis basado en el índice de salud ASAS

Background and aims: Sleep problems are common in spondyloarthritis (SpA), but the factors associated with them are only partially known. In this study, responses to item #16 from the Assessment of SpondyloArthritis international Society-Health Index (ASAS HI) that explores the sleep category according to the International Classification of Functioning, Disability and Health (ICF) were compared between psoriatic arthritis (PsA) and axial SpA (axSpA). Methods: Post hoc analysis of a multicentre cross-sectional study included a total of 201 consecutive patients. The prevalence, correlations, and disease factors associated with a positive response to item #16 were analyzed in both SpA populations. Results: Forty-eight/111 (43.2%) patients with axSpA and 42/90 (46.7%) with PsA reported sleep problems. There was a moderate–high correlation between item #16 and the ASAS HI sum score in both populations (r≥.59). In axSpA, poor sleep was associated with disease activity (OR 8.45, p<.001), biological therapy use (OR .24, p<.05) and CRP levels (OR .16, p<.05). In PsA, disturbed sleep was independently associated with disease activity showing a dose-response effect (OR 1.16, p<.001). Taking both populations together, disease severity (OR 6.33, p<.001) and axSpA (OR .50, p<.05) were independently associated with a positive response to item #16. Correlations between the different components of the ASAS HI and item #16 were markedly different in both populations. Conclusions: A positive response to item #16 was common in both SpA phenotypes. However, the link between inflammatory burden and disturbed sleep was higher in axSpA than in PsA. (AU)

Antecedente y objetivos: Los problemas del sueño son comunes en la espondiloartritis (SpA), pero los factores asociados a ellos solo se conocen parcialmente. En este estudio, se compararon las respuestas al ítem 16 de ASAS HI (Assessment of SpondyloArthritis International Society-Health Index) que explora la categoría del sueño, de acuerdo a ICF (International Classification of Functioning, Disability and Health) entre artritis psoriásica (PsA) y Spa axial (axSpA). Métodos: El análisis post hoc de un estudio transversal multicéntrico incluyó un total de 201 pacientes consecutivos. Se analizaron en ambas poblaciones de SpA la prevalencia, las correlaciones y los factores de la enfermedad asociados a la respuesta positiva al ítem 16. Resultados: Un total de 48/111 (43,2%) pacientes con axSpA y 42/90 (46,7%) con PsA reportaron problemas del sueño. Existió una correlación de modera a alta entre el ítem 16 y la puntuación acumulada de ASAS HI en ambas poblaciones (r≥0,59). En axSpA, el sueño escaso se asoció a la actividad de la enfermedad (OR 8,45, p<0,001), el uso de terapia biológica (OR 0,24, p<0,05) y los niveles de PCR (OR 0,16, p<0,05). En la PsA, la perturbación del sueño estuvo independientemente asociada a la actividad de la enfermedad, lo cual refleja un efecto dosis-respuesta (OR 1,16, p<0,001). Considerando ambas poblaciones conjuntamente, la severidad de la enfermedad (OR 6,33, p<0,001) y axSpA (OR 0,50, p<0,05) estuvieron asociadas de manera independiente a la respuesta positiva al ítem 16. Las correlaciones entre los diferentes componentes de ASAS HI y del ítem 16 fueron marcadamente diferentes en ambas poblaciones. Conclusiones: La respuesta positiva al ítem 16 fue común en ambos fenotipos de SpA. Sin embargo, el vínculo entre carga inflamatoria y perturbación del sueño fue mayor en axSpA en comparación con PsA. (AU)