Plasma heat shock protein 90 levels in patients with spondyloarthritis and their relation to structural changes: a cross-sectional study.

Aim: Heat shock protein 90 (Hsp90) is a molecular chaperone regulating immune response. We aimed to assess systemic Hsp90 as a biomarker for spondyloarthritis (SpA). Materials & methods: Total of 80 axial SpA (axSpA) and 22 psoriatic arthritis patients and a corresponding number of age- and sex-matched healthy controls (HC) were included. Plasma Hsp90 levels were measured by ELISA. Results: Hsp90 was significantly increased in axSpA patients compared with HC (median interquartile range: 15.7 [10.5-19.8] vs 8.3 [6.6-11.8] ng/ml, p < 0.001). Moreover, Hsp90 was superior to C-reactive protein in differentiating axSpA (and both radiographic axSpA [r-axSpA] and nonradiographic-axSpA) from HC. Hsp90 levels correlated with bone marrow edema of sacroiliac joints in r-axSpA patients (r = 0.594, p = 0.019). Conclusion: Hsp90 could become a biomarker for active inflammation in r-axSpA, and can better distinguish axSpA patients from healthy subjects than C-reactive protein.

[Biological treatment of psoriatic arthritis]. / Biologická lécba psoriatické artritidy.

Psoriatic arthritis (PsA) is a heterogeneous disease affecting, besides synovial joints, also the entheses, the soft tissues of the whole finger (dactylitis) and the axial skeleton. Currently the classification criteria CASPAR are used to diagnose PsA. In a large number of patients the disease leads to irreversible joint damage (X-ray, respectively clinical) which significantly reduces life quality and limits the patient in his/her everyday activities and also considerably limits their work capacity. There is evidence showing that early commencement of treatment and treat to target principle can significantly reduce this negative development. In recent time the knowledge of the disease pathogenesis has been extending and at the same time new drugs appear that act on the critical pathogenetic processes in a targeted way. These are biological drugs from the group of TNFα inhibitors and, most recently, also inhibitors of Th17 - IL17 pathway. Together with that is further specified the treatment strategy and the way of its monitoring. These new findings have led to the update of recommendations for the treatment and monitoring of psoriatic arthritis by the Czech Society for Rheumatology.Key words: biological drugs - conventional synthetic disease-modifying antirheumatic drugs - early treatment - psoriatic arthritis - targeted synthetic disease modifying drugs - treat to target.

Mapping Quality of Life (EQ-5D) from DAPsA, Clinical DAPsA and HAQ in Psoriatic Arthritis.

BACKGROUND: Clinical trials and observational studies lacking measures of health-related quality of life (QoL) are often inapplicable when conducting cost-effectiveness analyses using quality-adjusted life-years (QALYs). The only solution is to map QoL ex post from additionally collected clinical outcomes and generic QoL instruments. Nonetheless, mapping studies are absent in psoriatic arthritis (PsA). METHODS: In this 2-year, prospective, multicentre, non-interventional study of PsA patients, EQ-5D and key clinical parameters such as Disease Activity in PsA (DAPsA), clinical DAPsA (cDAPsA; DAPsA without C-reactive protein [CRP]), and Health Assessment Questionnaire disability index (HAQ) were collected. We employed a linear mixed-effect regression model (ME) of the longitudinal dataset to explore the best predictors of QoL. RESULTS: A total of 228 patients were followed over 873 appointments/observations. DAPsA, cDAPsA and HAQ were stable and highly significant predictors of EQ-5D utilities in both cross-sectional and longitudinal analyses. The best prediction was provided using a linear ME with HAQ and cDAPsA or DAPsA. A HAQ increase of 1 point represented a decrease in EQ-5D by -0.204 or -0.203 (p < 0.0001); a one-point increase in cDAPsA or DAPsA dropped EQ-5D equally by -0.005 (p < 0.0001). The ME revealed steeper and more accurate association compared with cross-sectional regressions or non-linear models/transformations. CONCLUSIONS: This is the first mapping study conducted in PsA and we hope that our study will encourage further mapping studies in PsA. The results showed that in cases where CRP is absent, cDAPsA provides similar results to DAPsA in predicting QoL.

Mapping the relationship between clinical and quality-of-life outcomes in patients with ankylosing spondylitis.

AIM: To map health-related quality of life (Qol) with clinical parameters BASFI and ASDAS-CRP measure, and other covariates. METHODS: Our prospective multicenter non-interventional observation study of ankylosing spondylitis (AS) collected data about QoL and clinical outcomes on the initial and four subsequent visits. We employed simple linear regression analysis of a cross-sectional dataset, and fixed effect, random effect and pooled linear regression of a longitudinal dataset. RESULTS: We showed that BASFI and ASDAS-CRP are very strong, robust predictors of EQ-5D utilities in all regression specifications together with sex (female), invalidity, and activity impairment. Additionally, the longitudinal regression analysis showed that a fixed effect model may be a viable alternative to the most commonly used random effect model or pooled linear regression due to the nature of our dataset. CONCLUSION: This is one of the first studies using a fixed effect model in longitudinal patient-level data, although, this method has been widely used in economics.

Elevated serum prolactin levels as a marker of inflammatory arthritis in psoriasis vulgaris.

BACKGROUND AND AIMS: Psoriasis vulgaris (PV) is complicated in up to 40% patients by the inflammatory joint disease psoriatic arthritis (PsA). Neither the aetiology of the arthritis nor specific laboratory markers for its disease activity have been clearly elucidated. Prolactin (PRL) acts as a cytokine with immunomodulatory functions and plays a role in skin and joint biology. The results on PRL however as a marker are unclear. The aim of this study was to confirm whether serum PRL levels reflect systemic complications of PV, like inflammatory joint disease and/or can serve as a marker of disease activity in both cases. METHODS: A total of 70 patients with PV without arthritis and 40 patients suffering from PsA were included. In all patients, we determined skin disease activity according to the PASI index and in PsA, active disease assessed as swollen or tender joints. The control group included 27 age and sex matched healthy individuals. The concentration of PRL in the serum was measured by immunoradiometric assays. RESULTS: The PRL serum levels were significantly increased in PsA patients (299.2±28.29 mIU/L) compared to PV only patients (201.4.2±11.72 mIU/L), P = 0.0003 and healthy individuals (198.2±15.31 mIU/L), P = 0.007. The serum PRL levels in PsA with active disease 336.8±42.50 (mIU/L) were higher than in PV and controls, P < 0.0001 and P = 0.002 respectively. In PV only patients, there was no correlation between PASI and PRL levels. CONCLUSION: Our results showed that PRL serum levels are a marker of active arthritis in PsA and reflects systemic complication rather than local skin activity.

Work Productivity and Costs Related to Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis.

OBJECTIVES: To determine and compare the impact of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis on work productivity, to calculate the productivity costs (PC), and to map out factors that influence (functional status and disease activity) work productivity. METHODS: The Work Productivity and Activity Impairment questionnaire was used to evaluate productivity losses of patients with RA (n = 77), AS (n = 230), and psoriasis (n = 93). Demographic data, patient-reported outcomes (PROs) (Health Assessment Questionnaire [HAQ] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and clinical parameters (Disease Activity Score in 28 joints [DAS28], body surface area [BSA], and Psoriasis Area and Severity Index [PASI]) were collected. The correlations among PROs, clinical parameters, and overall productivity loss were examined, and multiple regression models were used to examine relationships among parameters and productivity loss. PC were calculated using the friction cost approach. RESULTS: Mean patient age and disease duration were 47.1 and 15.7 years, respectively. The mean HAQ and DAS28 in patients with RA were 1.22 and 5.6, respectively. The mean BASDAI score in patients with AS was 4.43. The mean BSA and PASI score in patients with psoriasis were 21.1% and 12.9, respectively. The percentage of patients with psoriatic arthritis (in those with psoriasis) was 24.7%. We did not find significant differences in Work Productivity and Activity Impairment domains among various diagnoses. Patients with AS, RA, and psoriasis reported overall work productivity losses of 40.9%, 42.9%, and 42.8%, respectively. Daily activity impairments were approximately 50.0%. Overall work productivity loss strongly correlated with PROs, whereas correlations with clinical parameters were weak. The HAQ and BASDAI were identified as major predictors of productivity impairment. CONCLUSIONS: The greatest loss in productivity was in those with psoriatic arthritis; however, it was not significant. In contrast to clinical parameters (DAS28, BSA, and PASI score), PROs (HAQ and BASDAI score) significantly influence loss of productivity. The average annual lost PC per patient was estimated to be €2000.

Leflunomide in psoriatic arthritis: results from a large European prospective observational study.

OBJECTIVE: To determine the "real-world" clinical effectiveness and safety of leflunomide in patients with psoriatic arthritis (PsA). METHODS: This prospective, multinational 24-week observational study involved adult patients with active PsA who initiated treatment with leflunomide. Patients were evaluated at baseline, 12 weeks, and 24 weeks. The primary outcome was response as assessed by the Psoriatic Arthritis Response Criteria (PsARC) in patients with pre- and posttreatment data. A modified PsARC response analysis included patients with joint counts, but no severity scores. Other effectiveness evaluations included global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. All patients were evaluated for safety. RESULTS: A total of 514 patients were enrolled in this study (mean age 50.7 years, mean disease duration 6.1 years). In the primary effectiveness analysis, 380 (86.4%) of 440 patients (95% confidence interval 82.8%-89.4%) achieved a PsARC response at 24 weeks. Significant improvements were observed in tender and swollen joint scores and counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. The discontinuation rate was 12.3%. Ninety-eight adverse drug reactions occurred in 62 (12.1%) patients; 3 drug reactions were serious (2 increased liver enzymes, 1 hypertensive crisis). CONCLUSION: Leflunomide is an effective and well-tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease.

The HLA-Cw*06 allele and -1149 G/T polymorphism of extrapituitary promoter of PRL gene as a possible common genetic predisposing factors to psoriasis vulgaris and psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) affects approximately 30 % of patients suffering from psoriasis vulgaris (PsV), but the risk factors for its development have not been well elucidated yet. The HLA-Cw*06 allele was described as a predisposing factor to PsV. Prolactin is known as an immune response modulator, and its elevated levels present risk for PsV development. It is possible that these factors interact and together emphasize the predisposition to both diseases. We tested on an association of HLA-Cw alleles and functional polymorphism -1149 G/T in PRL gene extrapituitary promoter with PsV and PsA in Czech population. We found a statistically significant association between HLA-Cw*06 allele and PsV (P corrected = 0.0013) that was most prominent in early onset disease subtype (P corrected = 0.0013). The association between HLA-Cw*06 and PsA was low (P corrected = 0.0585) and restricted to PsA patients with early PsV onset (P corrected = 0.0195). We found no association of -1149 G/T PRL gene polymorphism with either PsV or PsA.

HLA-Cw*06 class I region rather than MICA is associated with psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which affects patients suffering from psoriasis. The genetic background especially the susceptibility loci on the short arm of the chromosome six contribute to PsA development. In our study, we looked for the role of the MICA and HLA-Cw genes polymorphisms in PsA pathogenesis. We investigated 100 PsA patients and 94 healthy Czech individuals. We found an association between HLA-Cw*06 and PsA namely PsA with psoriasis type I (age of psoriasis onset before 40 years) compared to healthy individuals (P (corrected) < 0.05, OR 2.56, CI 95% 1.33-4.76 and P (corrected) = 0.01, OR 3.03, CI 95% 1.53-5.88, respectively). The MICA-A9 allele of the transmembrane microsatelite MICA polymorphism occurred more frequently in PsA with psoriasis type II group (age of psoriasis onset after 40 years) than in controls, 58.6 versus 38.0%, respectively however, this finding did not reach a statistical significance after correction (P (corrected) = 0.085).