Long-term safety and efficacy of adalimumab in psoriasis: a multicentric study focused on infections (connecting study).

INTRODUCTION: This Italian multicenter retrospective study evaluated safety and efficacy of the anti-TNF drug, adalimumab, in a cohort of patients affected by tuberculosis (TB), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Psoriasis is an autoimmune disease affecting around 3% of the Italian population and associated with several comorbidities, including arthritis, cardio-metabolic diseases and depression. In its moderate-to-severe form, psoriasis profoundly impairs quality of life of patients. AIM: Therefore, these patients deserve systemic treatments including conventional DMARDS (disease modifying anti-rheumatic drugs) and biologics. Management of moderate and severe psoriasis patients affected by relevant infections such as TB, HBV, HCV and HIV may be difficult because of the toxicity of the conventional systemic treatment. MATERIAL AND METHODS: The CONNECTING study analysed 28 moderate to severe psoriasis patients infected by TB, HBV, HCV and HIV who were treated with adalimumab for up to 96 weeks together with respective prophylactic treatment. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 75% improvement in 91% of patients. Some of these patients (n = 9) were also affected by arthritic comorbidity. The patients experienced a rapid decrease in pain, measured by pain VAS (visual analogic scale) that reached 0 in all of them. Monitoring of the respective infection did not show any worsening or reactivation of infection or any severe adverse events during the entire observation period. CONCLUSIONS: Adalimumab is effective and safe in patients affected by these important infections.

Treatment of psoriasis with etanercept in immunocompromised patients: Two case reports.

Tumour necrosis factor (TNF)-α blocking agents have revolutionized the treatment of psoriasis and psoriatic arthritis. Concerns remain about increased susceptibility to infection and onset of malignancies, and the use of TNF-α agents in patients with HIV infection or undergoing immunosuppressant treatment is debated. We report cases of severe plaque psoriasis in a patient with HIV infection and in a liver transplant recipient who were successfully treated with etanercept, an anti-TNF-α agent, without notable side-effects.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL): a possible pathogenic role in chronic plaque psoriasis.

BACKGROUND: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine member of the tumour necrosis factor (TNF) family. Its role has been investigated in skin cancers and some inflammatory and/or immune-mediated skin diseases. An involvement of TRAIL in psoriasis pathogenesis has recently been hypothesized. We investigated the expression and localization of TRAIL and its receptors in psoriatic skin and measured serum TRAIL. The intracellular pathways activated by TRAIL were assessed to investigate its potential role in the pathogenesis of psoriasis. METHODS: Twenty-four consecutive patients with plaque psoriasis and age- and sex-matched healthy subjects were recruited. Serum TRAIL was measured by means of an enzyme-linked immunosorbent assay (ELISA). TRAIL and TRAIL receptors were evaluated by reverse transcription - polymerase chain reaction (RT-PCR) (RNA of lesional and non-lesional psoriatic skin) and by immunohistochemistry (lesional skin). Caspase 8 and NF-kB immunoexpression were also evaluated by immunohistochemistry. RESULTS: RT-PCR demonstrated increased synthesis of TRAIL and its receptors in lesional vs. non-lesional skin. Immunohistochemistry showed a strong staining of TRAIL and TRAIL receptors both in the epidermis and in the dermal infiltrate. Finally, a correlation emerged between caspase 8 and TRAIL immunoexpression in the dermis. CONCLUSIONS: Our findings suggest an involvement of TRAIL in psoriasis pathogenesis, probably through an action at the site of the inflammatory infiltrate, likely via caspase 8.

Efficacy and maintenance strategies of two-compound formulation calcipotriol and betamethasone dipropionate gel (Xamiol® gel) in the treatment of scalp psoriasis: results from a study in 885 patients.

BACKGROUND: Previous studies showed the efficacy of a formulation containing calcipotriol and betamethasone dipropionate for the treatment of psoriasis. OBJECTIVE: To investigate maintenance strategies of a formulation containing calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) for the treatment of scalp psoriasis. MATERIALS AND METHODS: Nine-hundred and four patients were screened and randomised on a 1:1 basis in two groups: maintenance of two applications per week (group A) versus on-demand therapy (group B). Clinical evaluation was performed at weeks 0, 2, 4, 8 and 12. RESULTS: Eight-hundred and eighty-five patients were randomised: 441 in group A and 444 in group B. From week 2, both groups showed a significant clinical improvement compared with baseline; at weeks 8 and 12, group A demonstrated a higher clinical response compared with group B (p < 0.05). This difference was statistically significant (OR 0.47, 95% CI 0.37, 0.60). CONCLUSIONS: The maintenance of twice-weekly application versus on-demand treatment of calcipotriol/betamethasone dipropionate gel is more effective and is associated with a lower rate of relapse.

Psoriatic patients have an increased risk of polycystic ovary syndrome: results of a cross-sectional analysis.

OBJECTIVE: To define the prevalence and the features of polycystic ovary syndrome (PCOS) in patients with psoriasis. To our knowledge, the association between PCOS and psoriasis has not been explored in previous studies. Psoriasis is linked with metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease, which are features often associated with PCOS. DESIGN: A cross-sectional analysis was performed between January 2010 and April 2012. SETTING: Unit of human reproductive pathophysiology, Catholic University Hospital. PATIENT(S): We prospectively analyzed 51 patients with psoriasis and 102 healthy age- and body mass index (BMI)-matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The prevalence and characteristics of PCOS women of reproductive age with chronic plaque psoriasis. RESULT(S): The prevalence of PCOS was greater in patients with psoriasis than in matched control subjects (47.05% and 11.76%, respectively; odds ratio, 6.66; 95% confidence interval 2.95-15.07). Among the women with psoriasis, the prevalence of Psoriasis Area and Severity Index ≥10 was higher in patients with PCOS than in subjects without PCOS (odds ratio, 3.5; 95% confidence interval 1.04-11.72). CONCLUSION(S): The prevalence of PCOS in women with psoriasis is remarkably greater than in age- and BMI-matched control women.

Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis.

The combination of etanercept, a tumour necrosis factor α inhibitor, with narrow-band ultraviolet B (NB-UVB) phototherapy has recently been reported to be effective in moderate-to-severe plaque psoriasis, yielding better results than either monotherapy. To assess the efficacy and safety of this combined treatment using the lower approved etanercept dosage. In this single-arm open-label study patients received etanercept 50 mg once weekly combined with NB-UVB phototherapy three times weekly for 8 weeks, followed by etanercept alone until week 12. We evaluated the proportion of patients achieving 75%, 90% and 100% improvement of their initial PASI score (PASI75, PASI90, and PASI100, respectively). Patients were 19 men and 14 women, mean age 48.3 years ± 12.1 standard deviation (SD) and mean baseline Psoriasis Area and Severity Index (PASI) score 22.5 ± 7.5. On treatment weeks 4, 8, and 12, 24.2%, 66.7%, and 81.8% of patients achieved PASI75; 8.0%, 15.1%, and 57.6% reached PASI90, and 0%, 6.0%, and 24.2% attained PASI100, respectively. There were no severe side effects. Low-dosage etanercept combined with NB-UVB phototherapy is an effective, safe and economical approach to treat moderate-to-severe plaque psoriasis. Further studies are clearly required to assess its long-term efficacy and safety.

Usefulness of ultrasound imaging in detecting psoriatic arthritis of fingers and toes in patients with psoriasis.

BACKGROUND: Given that clinical evaluation may underestimate the joint damage and that early treatment can slow down psoriatic arthritis (PsA) progression, screening psoriasis patients with imaging tools that can depict early PsA changes would entail clear benefits. OBJECTIVE: To compare the ability of X-ray and ultrasound (US) examination in detecting morphological abnormalities consistent with early PsA in patients with psoriasis, using rheumatological evaluation as the gold standard for diagnosis. METHODS: Patients with chronic plaque psoriasis and no previous PsA diagnosis attending our outpatient dermatology clinic and reporting finger/toe joint and/or tendon pain underwent X-ray and US evaluation; they were subsequently referred to a rheumatologist for clinical examination and review of imaging findings. RESULTS: Abnormal US and/or X-ray findings involving at least one finger and/or toe (joints and/or tendons) were seen in 36/52 patients: 11 had one or more X-ray abnormalities, including erosion, joint space narrowing, new bone formation, periarticular soft tissue swelling, and periarticular osteoporosis; 36 had suspicious changes on US. CONCLUSION: US proved valuable in detecting joint and/or tendon abnormalities in the fingers and toes of patients with suspicious changes. The dermatologist should consider US to obtain an accurate assessment of suspicious findings.

Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis.

BACKGROUND/AIMS: The association between NAFLD and psoriasis has never been explored in prospective epidemiological studies. The aim of this 2-phase study was to study the clinical features of NAFLD in patients with psoriasis. METHODS: Phase 1: Investigation of prevalence and characteristics of NAFLD in an unselected cohort of 142 adult Italian outpatients with psoriasis vulgaris. Phase 2: Comparison of the psoriasis cohort subgroup with NAFLD and an age- and body mass index-matched retrospective cohort of 125 non-psoriasis patients with biopsy proven NAFLD. RESULTS: Based on histories, laboratory tests, and ultrasound studies, 84 (59.2%) received clinical diagnosis of NAFLD; 30 had factors potentially associated with liver disease other than NAFLD (e.g., viral hepatitis, significant ethanol, methotrexate use); and 28 (19.7%) had normal livers. Comparison of the normal-liver and NAFLD subgroups revealed that NAFLD in psoriasis patients (Ps-NAFLD) was significantly correlated with metabolic syndrome (p<0.05); obesity (p=0.043); hypercholesterolemia (p=0.029); hypertriglyceridemia (p<0.001); AST/ALT ratio >1 (p=0.019), and psoriatic arthritis (PsA) (p=0.036). The association with PsA remained significant after logistic regression analysis (OR=3.94 [CI, 1.07-14.46]). Compared with the retrospective non-psoriatic NAFLD cohort (controls), Ps-NAFLD patients (cases) were likely to have severe NAFLD reflected by non-invasive NAFLD Fibrosis Scores and AST/ALT >1. CONCLUSIONS: NAFLD is highly prevalent among psoriasis patients, where it is closely associated with obesity (overall and abdominal), metabolic syndrome, and PsA, and more likely to cause severe liver fibrosis (compared with nonPs-NAFLD). Routine work-up for NAFLD may be warranted in patients with psoriasis, especially when potentially hepatotoxic drug therapy is being considered.