Antidrug antibody formation during tumor necrosis factor α inhibitor treatment of severe psoriatic patients in the real-life practice.

INTRODUCTION: Antidrug antibody (ADA) production may be the reason behind secondary inefficacy of anti-TNF-α therapy in psoriasis. AIM: To investigate the production of ADA, serum tumor necrosis factor α (TNF-α) and drug levels as predictors of clinical response in real-life circumstances. MATERIAL AND METHODS: Serum drug concentrations (TNFi), the presence of ADAs and serum TNF-α levels were measured in 158 patients by the ELISA method. Clinical response was evaluated by calculating PASI. Their correlation has been statistically analysed. RESULTS: In adalimumab and infliximab treated patients, ADA formation was observed in 18.4% and 33%, respectively, and the serum TNFi concentration was significantly higher in the ADA negative groups. In contrast there was no ADA formation detected among etanercept treated patients. The serum TNFi concentration was significantly lower among non-responders (n = 33). The serum TNF-α level was also measured and the correlation with the concentration of the serum TNFi level was analysed. Having evaluated the results of all patients together, the serum TNFi and TNF-α concentrations showed a significant negative correlation. However, when groups were analysed separately, in case of adalimumab, a significant negative correlation was detected between serum TNFi and TNF-α concentrations. With respect to infliximab, there was no significant correlation, and an inverse correlation was found in the etanercept group. The TNF-α levels and ADA positivity were significantly higher in non-responders. CONCLUSIONS: This study revealed the major role of ADAs against TNFi in case of secondary inefficacy in real-life circumstances. ADA levels show a stronger correlation with PASI failure than serum TNFi or TNF-α levels.

[Genitourethral infections caused by D-K serotypes of Chlamydia trachomatis]. / Chlamydia trachomatis D-K szerovariáns által okozott genitourethralis fertozések.

Sexually transmitted infections of the urogenital tract are most commonly caused by the intracellular bacteria Chlamydia trachomatis worldwide, resulting the clinical picture of acute urethritis in men as well as urethritis and endocervicitis in women. As women often present with few symptoms only or a completely symptom-free disease course, one of the most important long-term complications is chronic pelvic inflammatory disease often followed by the development of infertility caused by chronic scar formation. Well-organized screening programs are considered to have a leading role in the prevention of disease spreading and long lasting unwanted complications. Antibiotic treatment options are often influenced by special circumstances, such as pregnancy and several complicated clinical forms. The aims of the authors are to give a concise review on the current knowledge regarding Chlamydia trachomatis infections and summarize typical clinical signs, modern diagnostic techniques as well as accepted treatment protocols and basic aspects of screening.

[Disease burden of psoriasis associated with psoriatic arthritis in Hungary]. / Arthritis psoriaticával társuló középsúlyos és súlyos psoriasis betegségterhe Magyarországon.

INTRODUCTION: Psoriasis is a frequent, chronic, systemic immune-mediated disease mainly affecting the skin and joints. AIM: To assess health related quality of life and cost-of-illness in moderate to severe psoriasis associated with psoriatic arthritis. METHOD: A cross-sectional questionnaire survey was conducted at two academic dermatology clinics in Hungary. RESULTS: Fifty-seven patients (65% males) completed the survey with a mean age of 54.3±11.6 years and mean EQ-5D score of 0.48±0.4. Mean annual total cost was €8,977 per patient, of which 71% occurred due to biological therapy and 21% were indirect costs, respectively. Permanent work disability due to psoriasis accounted for €1,775 (95% of the indirect costs). Per patient costs of subgroups not receiving systemic therapy (21%), traditional systemic therapy (32%), and biological systemic therapy (47%) amounted to the sum of €1,729, €1,799, and €16,983, respectively. CONCLUSIONS: Patients on biological therapy showed significantly better health related quality of life. As for health economics, the efficacy of systemic treatments is appropriate to be assessed together in patients with moderate to severe psoriasis associated with psoriatic arthritis, since actual health gain might exceed that reported in psoriasis or psoriatic arthritis separately.

Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis.

A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.

Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases.

T lymphocytes expressing the CLA antigen constitute a subset of effector memory lymphocytes that are functionally involved in T-cell-mediated cutaneous diseases. Skin-seeking lymphocytes recirculate between inflamed skin and blood during cutaneous inflammation. Many studies in different T-cell-mediated inflammatory cutaneous diseases have clearly related their pathologic mechanisms to CLA+ T cells. Based on common features of these cells in different cutaneous disorders mediated by T cells, we propose that circulating CLA+T cells could constitute very useful peripheral cellular biomarkers for T-cell-mediated skin diseases.

Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study.

BACKGROUND: Psoriasis is associated with higher incidence of atherosclerotic comorbidities. Sustained arterial wall inflammation mediated by common cytokines of psoriasis and atherogenesis precedes atherosclerotic plaque development. Increased intima-media thickness (IMT) is an accepted indicator of subclinical atherosclerosis and has been reported in severe psoriasis. OBJECTIVE: This pilot study aimed to clarify whether effective long-term tumor necrosis factor-alfa inhibition decreases IMT in psoriasis. METHODS: In 16 patients with severe psoriasis, the Psoriasis Area and Severity Index score was calculated before therapy (etanercept, infliximab, adalimumab) and after 6-month treatment. Simultaneously, carotid and brachial IMT was measured by high-resolution, B-mode ultrasonography. Difference between initial and 6-month IMT values was determined for monitored arteries collectively and separately in carotid and brachial arteries. RESULTS: All of 16 patients achieved Psoriasis Area and Severity Index 75, and 14 of 16 achieved Psoriasis Area and Severity Index 90 improvement. In the group of patients without initial calcified atherosclerotic plaques (13 of 16) significant IMT decrease was detected when arteries were measured collectively (P = .0002). Initial and follow-up data differed significantly also at individual analysis of carotid (P = .011) and brachial (P = .006) arteries. Eleven of 13 patients had initial carotid IMT exceeding age-adjusted normal values. The other group (3 of 16) with initial manifest plaques showed increasing IMT tendency. Their baseline ultrasonography revealed carotid IMT above the upper limit of healthy adults' age-adjusted values. LIMITATIONS: Study limitation involves small patient numbers, self-controlled study design, and lack of patients' stratification according to common cardiovascular risk factors. CONCLUSION: In our pilot study effective tumor necrosis factor-alfa inhibition was found to decrease IMT in psoriatic patients without irreversible atherosclerotic plaques. Further analysis is recommended to confirm and complete our primary observations.

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres.

BACKGROUND: Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies. OBJECTIVES: To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary. METHODS: Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures. RESULTS: Two-hundred patients were involved (females 32%) with a mean age of 51 (SD 13) years, 103 (52%) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86%. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups. CONCLUSIONS: Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

Exploring the relationship between EQ-5D, DLQI and PASI, and mapping EQ-5D utilities: a cross-sectional study in psoriasis from Hungary.

BACKGROUND: There is a growing interest in policy making for using utility measures and identifying algorithms to convert disease-specific measures into utilities. OBJECTIVES: To analyse the relationship between EQ-5D, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) in psoriasis. To transform DLQI scores, and key clinical, demographic and health service utilisation variables into utilities. METHODS: A cross-sectional questionnaire survey of 200 consecutive adult patients with moderate to severe psoriasis was carried out in two Hungarian university clinics. The relationship between the outcome measures were analysed with correlations and with the known-groups method. Bivariate and multivariate regression algorithms on EQ-5D scores were formulated. RESULTS: The mean age of respondents was 51 years (SD = 12.9), 68.5% were male, and 51.5% received biological therapy. Median EQ-5D, DLQI, and PASI scores were 0.73, 3.0, and 3.45, respectively. EQ-5D showed a moderate correlation with the DLQI and with the PASI (r s = -0.48 and -0.43, p < 0.05). Strong correlation was found between DLQI and PASI (r s = 0.81, p < 0.05). DLQI and PASI discriminated better among groups categorised by the localisation of the lesions than EQ-5D. Presence of psoriasis on the neck and/or décolletage was associated with the greatest health related quality of life (HRQOL) impairment. Ten variables were incorporated in a multivariate algorithm that accounted for 48.8% of EQ-5D variance (ANOVA p < 0.001). CONCLUSIONS: This study provided the first evidence that patients with visible psoriatic lesions have significantly worse HRQOL compared to those with non-visible lesions, measured not only with DLQI but also with EQ-5D. In addition to demographic and clinical variables, our model included health service utilisation variables related to psoriasis, and explained higher proportion of EQ-5D variance than any previous findings in the literature.

Tissue-specific homing of immune cells in malignant skin tumors.

Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral non-lymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by non-lymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sézary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.