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1.
Expert Opin Biol Ther ; 23(12): 1307-1315, 2023.
Article in English | MEDLINE | ID: mdl-38108300

ABSTRACT

BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.


Subject(s)
Dermatitis, Atopic , Adult , Humans , Aged , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , Retrospective Studies , Goals , Cohort Studies , Quality of Life , Treatment Outcome , Antibodies, Monoclonal/adverse effects , Severity of Illness Index , Double-Blind Method
5.
Expert Opin Biol Ther ; 21(9): 1299-1310, 2021 09.
Article in English | MEDLINE | ID: mdl-34114515

ABSTRACT

Background: Information is limited from real-life studies evaluating the efficacy and safety of brodalumab.Research design and methods: In this real-life study, we retrospectively examined a database of 90 patients with moderate-to-severe psoriasis treated with brodalumab (210 mg, s.c.) and followed for 1 year. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 24, 36, and 48 weeks. Predictors of a PASI response were evaluated by logistic regression.Results: After 48 weeks, 92.2% of patients (mean age 50.2 ± 15 years) treated with brodalumab achieved a PASI score of <3. PASI score decreased from 17.4 ± 10.3 at baseline to 1.7 ± 3.9 and 1.4 ± 3.7 at 12 and 24 weeks, and PASI 75, 90, and 100 response was achieved in 87.3%, 81.8%, and 72.7% of patients, respectively, at 48 weeks.Univariate regression revealed that previous exposure to anti-IL17A treatment was associated with poorer PASI response between 36 and 48 weeks. In difficult-to-treat cases previously having failed with other biologics, brodalumab significantly improved outcome, leading to complete remission.Conclusion: Brodalumab was observed to be effective and safe in patients with moderate-to-severe chronic psoriasis in a real-world setting.


Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Adult , Aged , Humans , Middle Aged , Psoriasis/drug therapy , Retrospective Studies , Severity of Illness Index , Treatment Outcome
6.
Am J Clin Dermatol ; 22(4): 567-579, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33786754

ABSTRACT

BACKGROUND: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. METHODS: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. RESULTS: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418-0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257-1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. CONCLUSION: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower.


Subject(s)
Biological Products/therapeutic use , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Adult , Aged , Biological Products/pharmacology , Dermatologic Agents/pharmacology , Female , Follow-Up Studies , Humans , Interleukin-12/antagonists & inhibitors , Interleukin-12/immunology , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Interleukin-23/antagonists & inhibitors , Interleukin-23/immunology , Male , Middle Aged , Psoriasis/immunology , Remission Induction/methods , Retrospective Studies , Time Factors , Treatment Outcome
7.
J Eur Acad Dermatol Venereol ; 34(12): 2839-2845, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32401377

ABSTRACT

BACKGROUND: Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. OBJECTIVE: To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. METHODS: In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400 mg loading dose at 0, 2 and 4 weeks, followed by 200 mg every 2 weeks) for up to 52 weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). RESULTS: In the study were enrolled 153 patients (mean age: 55 years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P < 0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. CONCLUSION: Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.


Subject(s)
Arthritis, Psoriatic , Psoriasis , Arthritis, Psoriatic/drug therapy , Humans , Italy , Middle Aged , Psoriasis/drug therapy , Quality of Life , Retrospective Studies , Severity of Illness Index , Treatment Outcome
8.
Expert Opin Biol Ther ; 20(6): 665-672, 2020 06.
Article in English | MEDLINE | ID: mdl-32045273

ABSTRACT

Background: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions in psoriatic patients treated with an anti IL-17A agent (secukinumab or ixekizumab).Methods: Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.Results: Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.Conclusion: We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3-4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Drug Eruptions/pathology , Interleukin-17/immunology , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Drug Eruptions/drug therapy , Drug Eruptions/etiology , Female , Humans , Male , Middle Aged , Psoriasis/drug therapy , Retrospective Studies , Skin/pathology , Steroids/therapeutic use , Young Adult
10.
J Eur Acad Dermatol Venereol ; 32(10): 1737-1744, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29776016

ABSTRACT

BACKGROUND: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. OBJECTIVE: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. METHODS: In this multicentre study, psoriasis patients (N = 262) treated with an anti-TNF-alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. RESULTS: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. CONCLUSION: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF-alpha or IL-12/23 inhibitor.


Subject(s)
Adalimumab/therapeutic use , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Adult , Age Factors , Aged , Antibodies, Monoclonal/therapeutic use , Drug Substitution , Dyslipidemias/complications , Etanercept/therapeutic use , Female , Humans , Hypertension/complications , Infliximab/therapeutic use , Longitudinal Studies , Male , Metabolic Syndrome/complications , Middle Aged , Psoriasis/complications , Retrospective Studies , Severity of Illness Index , Time Factors , Ustekinumab/therapeutic use
11.
J Dermatolog Treat ; 28(8): 722-725, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28488449

ABSTRACT

BACKGROUND: Poor adherence to topical therapy, defined as the degree to which patients use medication as prescribed by their healthcare provider, represents a frequent cause of poor treatment outcomes. OBJECTIVE: To evaluate the impact of individualized medication training on efficacy, adherence and patient satisfaction to 4 weeks of a topical therapy in psoriasis. METHODS: All enrolled psoriatic patients were given a prescription for calcipotriol/betamethasone dipropionate gel once daily and were randomly assigned to one of the two following groups with a 1:1 allocation ratio. Patients in group 1 and group 2 underwent an initial visit, including the physical examination and provision of information by the dermatologist. Patients in group 2 also received an additional 20 min of individualized medication training. Efficacy, adherence and patient satisfaction were evaluated after 4 weeks of treatment. RESULTS: We enrolled 104 consecutive patients with psoriasis: patients in group 2, who were trained, had a significant improvement at week 4 in BSA, PASI, dPGA and higher PPQ score, and were more adherent compared to those in group 1 who were not trained. CONCLUSION: Individualized medication training on the correct application of a topical therapy from a healthcare professional may improve patients' adherence, treatment tolerability and clinical outcomes.


Subject(s)
Dermatologic Agents/therapeutic use , Patient Education as Topic , Psoriasis/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Betamethasone/analogs & derivatives , Betamethasone/therapeutic use , Calcitriol/analogs & derivatives , Calcitriol/therapeutic use , Drug Administration Schedule , Drug Combinations , Female , Humans , Linear Models , Male , Middle Aged , Patient Compliance , Patient Satisfaction , Psoriasis/pathology , Psoriasis/psychology , Quality of Life , Severity of Illness Index , Surveys and Questionnaires , Young Adult
12.
Int J Biochem Cell Biol ; 77(Pt A): 91-101, 2016 08.
Article in English | MEDLINE | ID: mdl-27267661

ABSTRACT

Matrix metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components. In particular, two members of this family named Gelatinase A and B, as amply documented in the literature, play a key role in the process of tumor growth/metastasis in breast and hepatocellular carcinoma. Their activity is regulated by Tissue Inhibitor of metalloproteinases-1 and -2, which are the physiological inhibitor of Gelatinases A and B respectively. The aim of this review is to determine the current understanding of the clinical and prognostic role of Metalloproteinases-2 and -9 and their inhibitors in the course of breast cancer and liver diseases. Forty-one articles were selected from PubMed by entering the following keywords: liver diseases, breast cancer, MMP-2, TIMP-2; all articles were read and notes were made regarding the number of enrolled patients, pathology, measures, results and these data were used to write this review. Over-expression of both gelatinases is associated with the relapse of disease, metastasis, shorter overall survival in breast cancer and hepatocellular carcinoma and invasion and progression to tumors in chronic liver diseases, and MMPs/TIMPs ratio could be useful in the follow-up of these patients.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Liver Neoplasms/diagnosis , Liver Neoplasms/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Animals , Breast Neoplasms/pathology , Humans , Liver Neoplasms/pathology , Prognosis
13.
J Eur Acad Dermatol Venereol ; 29(9): 1786-90, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25726968

ABSTRACT

BACKGROUND: Genetic factors might have a role for lack of therapeutic response to anti-TNF-alpha agents, as previously suggested in patients with rheumatoid arthritis and inflammatory bowel disease. OBJECTIVES: We evaluated the role of the main TNF-alpha polymorphisms (-238G>A, -308G>A, -857C>T) in predicting the response to etanercept, an anti-TNF-alpha fusion protein. MATERIAL AND METHODS: Genomic DNA was extracted from buccal epithelial cells in a series of 97 psoriatic patients who received etanercept for at least 3 months. Patients were classified as responders, if they achieved a PASI improvement ≥ 75% after 12 weeks of etanercept treatment, and non-responders, if PASI improvement was <75%. Single-nucleotide polymorphisms (SNPs) in TNF-alpha gene (-238G>A, -308G>A, -857C>T) were genotyped by PCR restriction fragment length polymorphism (RFLP) assays. RESULTS: We found that patients heterozygous (GA) for the -238G>A polymorphism were more likely not responsive to therapy compared to the GG genotype. In fact, the GA genotype was found in 5/59 (8.5%) responders and in 14/38 (36.8%) non-responders (P = 0.001). A significant relationship with therapy was also observed for the -308G>A polymorphisms. In fact, the GG, GA and AA genotypes were detected in 48 (81.4%), 9 (15.3%) and 2 (3.4%) of the 59 responders and in 22 (57.9%), 11 (28.9%) and 5 (13.2%) of the 38 non-responder patients (P = 0.03). No association with therapy was observed for the -857C>T polymorphisms. CONCLUSION: Our study supports the role of TNF-alpha polymorphisms in predicting the response to anti-TNF-alpha agents. In particular, we found that the presence of -238G>A and -308G>A polymorphisms is associated with poor response to a 3-month therapy with etanercept. However, our data have yet to be validated in larger cohorts.


Subject(s)
Arthritis, Psoriatic/genetics , DNA/genetics , Etanercept/therapeutic use , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/genetics , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/metabolism , Female , Follow-Up Studies , Gene Frequency , Genotype , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Polymerase Chain Reaction , Retrospective Studies , Spectrophotometry , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
14.
G Ital Dermatol Venereol ; 149(3): 355-61, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24819764

ABSTRACT

AIM: Psoriasis is a multifactorial chronic inflammatory skin disease that often occurs in patients who are overweight or obese. In literature the connections between obesity and eating disorders are well known, but few studies have investigated the link between eating disorders and psoriasis. We hypothesized that Eating Disorders (ED) can be considered a psychogenic cofactors, which contribute to the development of obesity and metabolic syndrome in psoriatic patients, who are frequently prone to psychiatric comorbidity. METHODS: From January to April 2011 we enrolled 100 consecutive psoriatic outpatients and a control group of 100 selected non-psoriatic outpatients, matched by age, gender, and BMI to the study group. The assessment battery was composed by the Psoriasis Area Severity Index (PASI) score, the Eating Disorder Inventory (EDI) and the Symptom Checklist-90 Revised (SCL-90-R®). RESULTS: Our data showed that most of EDI and SCL-90R subscales was mostly altered in psoriatic population compared to patients without psoriasis. Moreover, we noticed in patients with psoriasis an association between the progressive weight increase and an impairment on most of EDI subscales. CONCLUSION: Psoriasis is associated with psychopathological traits, which are frequently found in EDs. Since obesity makes psoriasis less susceptible to therapy and weight loss improves drug response, dermatologists should be alert to suspect the presence of this condition.


Subject(s)
Feeding and Eating Disorders/psychology , Metabolic Syndrome/psychology , Obesity/psychology , Psoriasis/psychology , Adult , Aged , Body Mass Index , Case-Control Studies , Feeding and Eating Disorders/complications , Female , Humans , Male , Metabolic Syndrome/etiology , Middle Aged , Obesity/etiology , Psoriasis/complications , Psoriasis/diagnosis , Psychiatric Status Rating Scales , Severity of Illness Index , Surveys and Questionnaires
15.
J Eur Acad Dermatol Venereol ; 28(5): 590-6, 2014 May.
Article in English | MEDLINE | ID: mdl-23506557

ABSTRACT

BACKGROUND: Endothelial function in psoriatic patients has been mainly evaluated through a high-resolution ultrasound measurement of flow-mediated vasodilation in the brachial artery, which is an operator-dependent and technically demanding technique: this characteristic, together with different patient selection criteria, could account for the conflicting results emerging from different studies. Recently, Circulating Endothelial Cells (CECs) level has been suggested as a novel biomarker of vascular injury. METHODS: The number of CECs was determined by a semi-automated immunomagnetic system (CellSearch system) in peripheral blood of psoriatic patients (n = 48) and healthy subjects (n = 50). In 15 patients, CEC level was also evaluated after 6 months of treatment with an anti-TNF-alpha agent, Etanercept. The plasma levels of high-sensitivity C-reactive Protein (CRP), E-selectin, VEGF and PAI-1 were measured by ELISA. The psoriasis severity was assessed by PASI score. RESULTS: A statistically significant difference (P = 0.001) was found between CEC level in psoriatic patients (10.6 ± 9.4 cells/mL) vs. the control group (3.9 ± 0.9 cells/mL). This count inversely correlated with sE-selectin levels (r(2) = 0.16; P = 0.03). After 6 months of therapy, patients experienced a significant (P < 0.05) decrease in CEC levels (3.4 ± 1.3 cells/mL) and in PASI score (from 11.7 ± 8.1 to 2.1 ± 4.0). CONCLUSIONS: The elevated CECs level that we found in a sample of high selected psoriatic patients could be expression of endothelial damage. Lowering of CECs count after treatment with Etanercept support the hypothesis that an effective systemic therapy of psoriasis may also improve the endothelial function.


Subject(s)
Endothelial Cells , Immunoglobulin G/therapeutic use , Psoriasis/blood , Receptors, Tumor Necrosis Factor/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Case-Control Studies , Etanercept , Female , Humans , Immunoglobulin G/pharmacology , Immunomagnetic Separation , Male , Middle Aged , Psoriasis/drug therapy
16.
G Ital Dermatol Venereol ; 148(2): 175-84, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23588143

ABSTRACT

Extra-intestinal manifestations are a relatively common complications of Inflammatory Bowel Diseases (IBD) and skin is one of the organs most commonly affected. Cutaneous findings in IBD patients may be related to different pathogenetic mechanisms and in some cases the etiologic link has not been fully elucidated. In particular, this is the case of psoriasis and erythema nodosum, two of the most frequent skin diseases observed in IBD patients. Aim of this paper was to review the epidemiology and the possible pathogenetic mechanisms implicated in the occurrence of these two dermatosis. In particular, an association between IBD and psoriasis has been observed in several epidemiological studies: psoriasis occurs in about 1-2% of the general population, compared with 3-11% of patients with IBD. Several studies have also evaluated the prevalence of IBD in psoriatic patients, with contrasting results. A common pathogenic pathways between these two conditions seems to be sustained by the responsiveness to therapy with biological treatments, such as anti-Tumor Necrosis Factor (TNF)-alpha agents and ustekinumab (a monoclonal antibody against p40 subunit common to IL-12 and IL-23). On the other hand, although usually idiopathic in half of the patients, erythema nodosum has been associated with a variety of disorders and conditions and IBD accounts for 1-4% of cases.


Subject(s)
Erythema Nodosum/complications , Inflammatory Bowel Diseases/complications , Psoriasis/complications , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Dermatologic Agents/therapeutic use , Erythema Nodosum/drug therapy , Erythema Nodosum/epidemiology , Evidence-Based Medicine , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Italy/epidemiology , Prevalence , Psoriasis/drug therapy , Psoriasis/epidemiology , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Ustekinumab
17.
J Eur Acad Dermatol Venereol ; 27(8): 1003-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22788697

ABSTRACT

BACKGROUND: Despite recent advances in the treatment of psoriasis, the therapeutic options for nail psoriasis are very limited, particularly when this is the only manifestation of the disease. OBJECTIVE: We performed a randomized controlled open-label study to assess the efficacy and safety of a topical treatment with tacrolimus 0.1% ointment in nail psoriasis. METHODS: In each patient, tacrolimus 0.1% ointment was prescribed for application only on the affected nails of a randomly selected hand for 12 weeks, whereas nails of the other hand did not receive any treatment. Severity of nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI) score. RESULTS: We enrolled 21 consecutive psoriatic patients. At week 12, a statistically significant (P < 0.001) improvement was obtained in the treated hands with respect to the hands used as control (NAPSI score absolute change 13.0 and 3.0 respectively). Each of the enrolled patients concluded the period of treatment, but one patient was withdrawn from tacrolimus application after 9 weeks because of the appearance of acute paronychia. DISCUSSION: Our study showed that tacrolimus 0.1% ointment may be an efficacious and safe therapeutic opportunity in the treatment of nail psoriasis. Our data should be confirmed by a double-blind study with a larger sample of patients.


Subject(s)
Immunosuppressive Agents/administration & dosage , Nail Diseases/drug therapy , Psoriasis/drug therapy , Tacrolimus/administration & dosage , Humans , Immunosuppressive Agents/therapeutic use , Ointments , Tacrolimus/therapeutic use
18.
Curr Med Chem ; 19(7): 938-44, 2012.
Article in English | MEDLINE | ID: mdl-22214462

ABSTRACT

Angiogenesis and signaling through the RAS/RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea BAY 43-9006, is an orally administered multikinase inhibitor with activity against RAS/RAF kinases multikinase inhibitor with activity against RAF kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.


Subject(s)
Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Pyridines/therapeutic use , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Drug Discovery , Humans , Inhibitory Concentration 50 , Molecular Structure , Niacinamide/analogs & derivatives , Phenylurea Compounds , Sorafenib
19.
Br J Dermatol ; 161(2): 306-12, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19485996

ABSTRACT

BACKGROUND: Pruritic dermatoses of the elderly often pose a diagnostic and therapeutic challenge. Specifically, a prodromal phase of bullous pemphigoid (BP) has to be considered in patients with pruritic lesions of polymorphic appearance. These conditions frequently do not fulfil all the clinical, histological and immunopathological criteria for establishing the diagnosis of BP. OBJECTIVES: To investigate IgG reactivity against the autoantigens of BP, BP180 and BP230, by enzyme-linked immunosorbent assay, in elderly patients affected with various pruritic disorders who had never experienced clinically apparent blisters. METHODS: The sera of 15 elderly patients with pruritic disorders (group I) were tested for IgG reactivity against BP180 and BP230. Also included were 30 patients with full-blown BP (group II) and 25 age-matched patients with immediate-type allergic reactions (group III). RESULTS: Thirty-three per cent of the patients with pruritic disorders (group I) showed IgG against BP230 and/or BP180: four of 15 patients had IgG against BP230 while two of the 15 group I patients were BP180 reactive. All the BP sera (group II) showed IgG reactivity against BP180 and/or BP230. Notably, two of 25 control sera (group III) showed IgG reactivity against either BP180 or BP230. CONCLUSIONS: The present findings suggest that IgG reactivity against BP230 (i.e. the COOH terminus), and to a lesser extent against BP180, is a common finding in pruritic disorders of the elderly with a wide clinical spectrum. IgG-mediated autoimmunity against the intracellular BP230 may facilitate a chronic, inflammatory response eventually leading to full-blown BP which is presumably associated with IgG against BP180.


Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Carrier Proteins/immunology , Cytoskeletal Proteins/immunology , Immunoglobulin G/immunology , Nerve Tissue Proteins/immunology , Non-Fibrillar Collagens/immunology , Pemphigoid, Bullous/immunology , Pruritus/immunology , Aged , Aged, 80 and over , B-Lymphocytes/immunology , Dystonin , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lymphocyte Activation/immunology , Male , Skin/immunology , Collagen Type XVII
20.
Int J Immunopathol Pharmacol ; 22(4): 961-6, 2009.
Article in English | MEDLINE | ID: mdl-20074459

ABSTRACT

Psoriasis is a chronic inflammatory skin condition characterized by inflammatory dermal infiltrate and hyperproliferative keratinocytes. The pathogenesis of this disease is mediated by a dysregulation of the innate immunity and cytokine production. Tumor necrosis factor alpha (TNFalpha) is considered the most important cytokine involved in the pathological mechanism of psoriasis. Recently, several therapies have been introduced for the treatment of psoriasis that try to block TNF alpha activity. Among these treatments etanercept is a fusion protein that specifically targets TNF alpha. We performed a study on twelve psoriatic patients aimed at evaluating the effect of etanercept treatment on the production and expression of TNFalpha and its receptors, in lesional and uninvolved psoriatic skin. We demonstrated that after three month of etanercept treatment at 50 mg/wk, TNF, TNF-RI and TNF-RII immunostaining in lesional and non-lesional skin samples of patients was greatly reduced, suggesting that this treatment not only acts on stable lesional plaques, but also at a very early stage of the disease.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dermatologic Agents/therapeutic use , Immunoglobulin G/therapeutic use , Psoriasis/drug therapy , Receptors, Tumor Necrosis Factor, Type II/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor/therapeutic use , Skin/drug effects , Tumor Necrosis Factor-alpha/metabolism , Adult , Biopsy , Down-Regulation , Etanercept , Female , Humans , Immunohistochemistry , Male , Middle Aged , Psoriasis/immunology , Psoriasis/pathology , Skin/immunology , Skin/pathology , Time Factors , Treatment Outcome
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