Effectiveness of etanercept biosimilar SB4 in maintaining low disease activity in patients with psoriatic arthritis switched from etanercept originator: an open-label one year study.

Background: Currently, there are no studies specifically aimed at investigating the effectiveness of etanercept biosimilar SB4 in psoriatic arthritis (PsA).Objectives: Our primary objective was to verify the ability of SB4 to maintain low disease activity in patients switching from reference etanercept to SB4 after 1 year of treatment with this last drug.Methods: Eighty-seven PsA patients with low disease activity at baseline measured by using the clinical Disease Activity Index for Psoriatic Arthritis ≤ 13 (cDAPSA; range 0-154) were prospectively evaluated after 6 and 12 months when switching from the reference etanercept to SB4.Results: One year after switching from the reference etanercept to SB4, 76 (87.3%) out of 87 patients maintained a cDAPSA ≤ 13.Conclusions: SB4 was effective in maintaining a state of low disease activity in the majority of patients switched from the reference etanercept. However, the proportion of patients (11 subjects) who failed to maintain a state of low disease activity at the end of the study was statistically significant. Loss of effectiveness in the above subjects was mainly due to subjective evaluations given by the patients, rather than an objectifiable exacerbation of disease.

Clinical remission of psoriatic arthritis in patients receiving continuous biological therapies for 1 year: the experience of an outpatient dermatological clinic for psoriasis.

BACKGROUND: The data in the literature concerning the frequency of remission of inflammatory arthritis in patients with psoriatic arthritis (PsA) are limited and conflicting. AIM: To evaluate the frequency of clinical remission in inflammatory arthritis in a cohort of patients with PsA receiving continuous treatment (1 year) with tumour necrosis factor-α inhibitors or ustekinumab, as well as the clinical covariates affecting remission. METHODS: We retrospectively evaluated 74 patients with PsA attending our psoriasis outpatient dermatology clinic. Remission of PsA was defined as documented absence of clinical signs related to arthritis (no tender or swollen joints), enthesitis or dactylitis. Patients were examined every 3 months for 1 year. RESULTS: At 1 year > 40% of patients had clinical remission of inflammatory arthritis. Predictors of remission were absence of fibromyalgia (FM) at baseline and having < 11 tender joints. CONCLUSIONS: Clinical remission of inflammatory arthritis can be obtained in a significant proportion of patients by continuous treatment with biological drugs. A large number of tender joints and the presence of FM can make remission less likely.

Immunologic biomarkers for clinical and therapeutic management of psoriasis.

BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.

hMena: altered expression in psoriatic skin.

Psoriasis is a chronic inflammatory skin disease, characterized by an enhanced proliferation and a deregulated differentiation of keratinocytes. hMena is an actin regulatory protein involved in the control of cell motility and adhesion. hMena results up-modulated in several human tumors with respect to normal tissues and its expression has been positively correlated to proliferation rate, tumor size and aggressiveness in response to mitogenic stimuli, such as epidermal growth factor. The hyperproliferation of keratinocytes observed in psoriasis prompted us to evaluate hMena expression on biopsies collected from involved and uninvolved skin of 12 patients with active plaque-type psoriasis with respect to healthy skin. We analyzed the expression of hMena at transcript and protein levels by quantitative RT-PCR and immunohistochemistry. We correlated the expression of hMena to Ki67 proliferation index and to keratin 10 (K10) and keratin 16 (K16) used as markers of keratinocyte differentiation and activation. We demonstrated the expression of hMena in a hyperproliferative skin condition not related to neoplastic transformation. Interestingly, we observed that hMena is not expressed in healthy skin, but it becomes detectable in non-lesional areas and it is even more expressed in lesional psoriatic skin. In addition, we found that hMena expression is correlated to the rate of keratinocyte proliferation and activation. Hence, our observations indicate hMena as a new possible player, involved in the development and/or maintenance of the hyperproliferative state of psoriatic keratinocytes.

Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma.

Bevacizumab is a recombinant humanised monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The drug, alone or in combination with other anticancer agents, has been shown to be effective against several types of neoplasms. We report a case of a woman with a history of severe psoriasis who developed psoriatic arthritis during a course of bevacizumab, which was administered for a malignant glioma.

The diagnosis of early psoriatic arthritis in an outpatient dermatological centre for psoriasis.

BACKGROUND: Most of the data currently available on early psoriatic arthritis (EPsA) derive from studies performed in rheumatological settings. However, in recent years, there has been an increase in the amount of data from dermatologic centres. OBJECTIVES: To describe the prevalence, clinical, laboratory and imaging characteristics of psoriatic patients with EPsA seen at a dermatological outpatient psoriasis centre. METHODS: From January 2007 to May 2010, all patients with psoriasis who visited the psoriasis centre were asked about inflammatory joint involvement. A diagnosis of psoriatic arthritis was made on the basis of clinical, laboratory and imaging studies. The patients were diagnosed with early PsA (EPsA) if their inflammatory articular symptoms had been present for ≤ 1 year. RESULTS: We diagnosed EPsA in 33 patients. Joint involvement was polyarticular (>5 joints involved) in 20 patients (60.6%) and oligoarticular (≤5 joints involved) in the remaining 13 patients. Quality of life due to skin involvement and the degree of functional impairment due to joint inflammation were only mildly affected, as measured by DLQI and HAQ, respectively. A direct correlation between the number of tender joints (ACR 68) and HAQ was found (r = 0.36; P = 0.04). Imaging studies showed that in spite of the absence of radiologic findings of peripheral joint damage, ultrasonography and contrast enhanced ultrasonography showed signs of articular inflammation in all patients. CONCLUSIONS: A diagnosis of EPsA can be correctly performed in a dermatologic outpatient facility. To do so, a close collaboration among dermatologists, rheumatologists and radiologists is necessary.

High prevalence of latent tuberculosis infection in autoimmune disorders such as psoriasis and in chronic respiratory diseases, including lung cancer.

The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

[Evidence-based guidelines and nephrological clinical practice: the GRADE system for rating of evidence]. / Applicabilità delle Linee Guida basate sull'evidenza e alla comune pratica clinica: il sistema GRADE.

It has become widely accepted that decision-making should be based on the best available evidence. The preparation of evidence-based guidelines in the interest of improving long-term outcomes has been a challenging task for many societies. Although nephrology is a relatively young medical discipline and therefore presumably well-disposed towards evidence-based decision making, many problems exist and evidence-based approaches to guidelines have also been widely criticized. One key issue has been the availability of only few and suboptimal randomized trials in this discipline. Considerable variation in the grading systems used to assess existing evidence in nephrology guidelines highlights the need for a better tool. Tools that rigidly assess existing evidence need to also explore the applicability to current practice. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, developed and implemented in 2004 by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines panel, is the most advanced tool in this direction.

Clinical outcome measures of psoriasis.

Several tools have been introduced in clinical trials to quantify the severity and the response to a given therapeutic regimen of both psoriasis and psoriatic arthritis. Each method present specific advantages and limitations. Here we will discuss some of the most popular clinical outcome measures of both psoriasis (Psoriasis Severity Index, Physician Global Assessment, National Psoriasis Fundation-Psoriasis Score, Dermatology Life Quality Index) and psoriatic arthritis (American College Rheumatology response criteria, Psoriatic Arthritis Response Criteria).

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA) are considered to be equally effective for patients with diabetic kidney disease (DKD), but renal and not mortality outcomes have usually been considered. OBJECTIVES: To evaluate the benefits and harms ACEi and AIIRA in patients with DKD. SEARCH STRATEGY: We searched MEDLINE (1966 to December 2005), EMBASE (1980 to December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 4 2005) and contacted known investigators. SELECTION CRITERIA: Studies comparing ACEi or AIIRA with placebo or each other in patients with DKD were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I(2) test, subgroup analyses and random effects metaregression. MAIN RESULTS: Fifty studies (13,215 patients) were identified. Thirty eight compared ACEi with placebo, five compared AIIRA with placebo and seven compared ACEi and AIIRA directly. There was no significant difference in the risk of all-cause mortality for ACEi versus placebo (RR 0.91, 95% CI 0.71 to 1.17) and AIIRA versus placebo (RR 0.99, 95% CI 0.85 to 1.17). A subgroup analysis of studies using full-dose ACEi versus studies using half or less than half the maximum tolerable dose of ACEi showed a significant reduction in the risk of all-cause mortality with the use of full-dose ACEi (RR 0.78, 95% CI 0.61 to 0.98). Baseline mortality rates were similar in the ACEi and AIIRA studies. The effects of ACEi and AIIRA on renal outcomes (ESKD, doubling of creatinine, prevention of progression of micro- to macroalbuminuria, remission of micro- to normoalbuminuria) were similarly beneficial. Reliable estimates of effect of ACEi versus AIIRA could not be obtained from the three studies in which they were compared directly because of their small sample size. AUTHORS' CONCLUSIONS: Although the survival benefits of ACEi are known for patients with DKD, the relative effects on survival of ACEi with AIIRA are unknown due to the lack of adequate direct comparison studies. In placebo controlled studies, only ACEi (at the maximum tolerable dose, but not lower so-called renal doses) were found to significantly reduce the risk of all-cause mortality. Renal and toxicity profiles of these two classes of agents were not significantly different.

Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis.

We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.

Antimicrobial agents and catheter-related interventions to prevent peritonitis in peritoneal dialysis: Using evidence in the context of clinical practice.

BACKGROUND: Peritonitis still represents a common and major complication of peritoneal dialysis. The broader adoption of several strategies, including antimicrobial and catheter related interventions, has been advocated to prevent or reduce the risk of peritonitis in peritoneal dialysis. METHODS: In this article we start with the presentation of a clinical case where concern exists about the strategies for preventing peritoneal dialysis peritonitis. We then look at the available evidence in the form of systematic reviews of randomized trials and individual randomized trials of interventions to prevent peritonitis in peritoneal dialysis. A summary of the evidence is provided and then put in context with the clinical case scenario. RESULTS: Nineteen eligible trials (1949 patients) of antimicrobial agents and 37 (2822 patients) of catheter related interventions to prevent peritonitis in peritoneal dialysis were identified. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (1 trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). As for antimicrobial strategies, perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (4 trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (3 trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). As for catheter related strategies, Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. CONCLUSIONS: Evidence exists to support the use of perioperative intravenous antibiotic prophylaxis at the time of catheter placement, the twin-bag and Y-set system, as well as prophylaxis with mupirocin in Staphylococcus aureus nasal carriers. Despite lack of evidence, several other agents are used and recommended in major international guidelines, which is reasonable but requires further investigation.

Simultaneous occurrence of linear scleroderma and homolateral segmental vitiligo.

Localized scleroderma and vitiligo only rarely have been reported to occur simultaneously. Here we report a case of a 21 year old man affected with both linear scleroderma of the left upper limb and homolateral segmental vitiligo of the trunk. Since the two diseases appeared during the same period, involved the same side of the body and their progression paralleled, a possible non-coincidental association between these two diseases is discussed.

Early but not lasting improvement of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease) after infliximab therapy: relationships with variations in cytokine levels in suction blister fluids.

Subcorneal pustular dermatosis (SCPD) is an uncommon disorder, characterized by a chronic relapsing vesiculopustular eruption, mainly involving the trunk and intertriginous areas, and usually seen in women > 40 years old. Various therapies have been reported to be effective in treating SCPD, such as dapsone, systemic glucocorticoids, acitretin, etretinate, infliximab and phototherapy. We report a case of a 54-year-old woman affected by SCPD who after failure of different therapies showed a dramatic but only temporary improvement of her disease during a cycle of therapy with infliximab. In addition, an array of cytokines was simultaneously measured in suction blister fluids obtained from involved or uninvolved skin at various time intervals during the first 12 weeks of observation.