Andrea Chiricozzi

IL-17 targeted therapies for psoriasis

Introduction: Psoriasis is a chronic, disabling, inflammatory skin disease whose pathogenesis still remains to be fully elucidated. Genetic and environmental factors induce an immune response mediated by several cytokines and chemokines, including IL-17A. Areas covered: Emerging evidence now suggests that IL-17A is central in the pathogenesis of psoriasis. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are in development and are being studied in Phase III clinical trials to evaluate their overall efficacy and safety. However, Phase II results of IL-17 blockade with each of these agents has shown a marked improvement of disease severity, thus confirming the pathogenic relevance of IL-17 in mediating crucial inflammatory circuits in psoriasis. Expert opinion: Anti-IL-17 agents are likely to become important future therapeutics in this disease and the may potentially impact on cardiovascular diseases, arthritis and other comorbidities associated with psoriasis.

Role of IL-23 in the pathogenesis of psoriasis: a novel potential therapeutic target?

Introduction: Psoriasis is a chronic inflammatory skin disorder determined by the activation of several immune cells and resident tissue cells. Various cytokines mediate inflammatory signals, including IL-23, which is an important factor involved in the differentiation of T helper (Th17) cells. Areas covered: Increasing evidence suggests that IL-23 is a central cytokine to the pathogenesis of psoriasis. An overview on both experimental and human data will be reported in order to support the hypothesis of a key pathogenic role of IL-23/Th17 axis. Expert opinion: Targeting IL-23 might be a more selective, valid and effective therapeutic approach, which, potentially, may show important advantages in terms of long-term efficacy and safety in the treatment of psoriasis.

Emerging applications of nanomedicine in dermatology.

Nanotechnology is a new branch of engineering consisting of the usage of nanoscale particles (100 nm and smaller). Nanomedicine is the application of nanoscale technologies for diagnostic and therapeutic purposes in medicine. Nanodermatology, nanotechnology applied to dermatology, represents one of the most advanced field for which an increasing interest, both economic and scientific, is rising.

Tofacitinib for the treatment of moderate-to-severe psoriasis

Because of the increased knowledge about the underlying cytokine network in psoriasis, selective systemic agents for the treatment of moderate-to-severe psoriasis have been developed during the past decade. The marked upregulation of JAK/STAT pathways in psoriasis and the identification of multiple key mediators in psoriasis pathogenesis that signal through JAK/STAT pathways led to investigation of JAK proteins as potential therapeutic targets for psoriasis treatment. A novel JAK-STAT inhibitor, tofacitinib, has been tested in preclinical studies for the treatment of psoriasis. Considering the satisfactory safety profile and the encouraging efficacy observed in the Phase II and Phase III trials, tofacitinib may represent an important therapeutic to be included into the psoriasis paradigm.

An occlusive dressing containing betamethasone valerate 0.1% for the treatment of prurigo nodularis

Abstract Introduction: Prurigo nodularis is a distressing condition characterized by the presence of multiple nodules associated with intense pruritus. Objective: To assess the clinical efficacy and safety of betamethasone valerate 0.1% tape and a moisturizing itch-relief cream in prurigo nodularis. Methods: Twelve patients were enrolled in this pilot comparison of betamethasone valerate 0.1% tape versus a moisturizing itch-relief cream containing feverfew. The study period was 4 weeks. Clinical evaluation was performed weekly. Results: Eleven subjects completed the 4 weeks of therapy. The mean visual analogue scale (VAS) for pruritus at baseline was 8.75 for both sides of the body. The side treated with betamethasone valerate 0.1% tape showed a higher clinical response (VAS score at week 4: 3.9; p < 0.005) compared with the side treated with moisturizing itch-relief cream (VAS score at week 4: 5.6; p < 0.005). Conclusion: Both treatments were effective. However, the occlusive dressing enhanced the efficacy of the treatment, preventing scratching.

New topical treatments for psoriasis

Introduction: Psoriasis is a common immune-mediated disorder that in 70% of cases appears in mild or mild-to-moderate form. Psoriasis is usually treated with topical medications and/or phototherapy with variable efficacy in controlling the disease. Areas covered: For the past three decades, research has been focused on systemic agents for the treatment of moderate-to-severe psoriasis, particularly with the introduction of biologic agents or ‘small molecules’. In parallel, novel advances in topical antipsoriatic agents have been made, experiencing a ‘new era’, with the development of new formulations and the identification of new therapeutic targets. These agents, having a different spectrum of action from traditional agents, are actually being tested in pre-marketing clinical trials and they may potentially represent promising treatment options that could enlarge the therapeutic armamentarium for the treatment of psoriasis. Expert opinion: Future antipsoriatic topical agents show new modality of action in blocking the pathogenic process leading to psoriatic plaque formation.

Psoriasis Phenotype in Inflammatory Bowel Disease: A Case-Control Prospective Study.

BACKGROUND AND AIMSnWhether inflammatory bowel disease [IBD] is associated with specific psoriasis phenotypes is undefined. In a case-control prospective study, we aimed to assess the severity and phenotype of psoriasis in IBD vs matched non-IBD controls with psoriasis [non-IBD].nnnMETHODSnFrom 2011 to 2013, dermatological assessment was performed in all IBD patients showing lesions requiring characterisation. In patients with psoriasis, assessment included: presence, characteristics, and severity. Each IBD patient with psoriasis was matched [gender, ethnicity, age ± 5 years] with one non-IBD patient with psoriasis.nnnSTATISTICAL ANALYSISndata were expressed as median [range], chi-square, Students t test.nnnRESULTSnDermatological assessment was performed in 251 IBD patients [115 females, age 47 [16-85]; IBD duration 9 years [1-46]]: 158 Crohns disease [CD] [63%], 93 ulcerative colitis [UC] [37%]. Psoriasis was detected in 62 [25%] IBD patients: 36 [58%] CD, 26 UC [42%; p = 0.44]. Clinical characteristics were comparable between IBD patients with or without psoriasis: age 50 [23-72] vs 47 [16-85]; IBD duration 9.5 [1-46] vs 9 [1-41]; p = non-significant]. The non-IBD group included 62 patients with psoriasis: 35 male; age 47 [18-75]. Mild psoriasis was more frequent in IBD vs non-IBD [87% vs 53%; p < 0.0001], whereas moderate and severe psoriasis were more frequent in non-IBD vs IBD [37% vs 13%, p = 0.004; 10% vs 0%; p = 0.036]. Plaque-type psoriasis was the most common phenotype in both IBD and non-IBD [p < 0.0001 vs others phenotypes].The frequency of plaque-type, nail psoriasis and psoriatic arthritis was lower in IBD vs non-IBD [p = 0.008; p < 0.0001; p = 0.006]. Psoriasis occurred after anti-tumour necrosis factor [TNF]α treatment in six CD patients [7%].nnnCONCLUSIONSnSeverity and phenotypes of psoriasis may differ between patients with IBD and their matched non-IBD controls.

Apremilast for the treatment of psoriasis

Introduction: Psoriasis is a chronic inflammatory skin disease characterized by dysregulation of the immune system and release of pro-inflammatory mediators. Drugs available for psoriasis show some limits as tolerability and route of administration. Apremilast, Otezla®, is an oral small molecule recently approved for the treatment of patients with moderate-to-severe plaque psoriasis. Compared to biologics that target a single cytokine, apremilast, degrading phosphodiesterase 4 (PDE4), interferes with cyclic anti-microbial peptides, which is involved in the transduction of intracellular signals, controlling the balance of pro-inflammatory and anti-inflammatory signals. Areas covered: This review reported the latest data available from Phase I, II and III trials on apremilast for the treatment of plaque psoriasis. A focus on the clinical management of apremilast, safety and clinical efficacy based on two pivotal clinical trials (ESTEEM 1 and ESTEEM 2) currently ongoing was described. A systematic search was conducted using the PubMed Medline database for primary articles. Expert opinion: Apremilast treatment was demonstrated effective and well tolerated in Phase II and III clinical trials. Several drug peculiarities, such as the low frequency of adverse events and the oral route of administration, make apremilast an innovative treatment for moderate-to-severe psoriasis.

A new therapeutic for the treatment of moderate to severe plaque psoriasis: apremilast

SUMMARY Psoriasis is a common, chronic, inflammatory skin disease. Being a life-long condition, a prolonged and safe control of the disease is needed. Current anti-psoriatic treatments show some limits in terms of tolerability and route of administration. Recently, a new oral small molecule, apremilast, has been approved for the treatment of patients with moderate-to-severe plaque psoriasis. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that regulates the transduction of intracellular signals, including pro-inflammatory and anti-inflammatory pathways. Because of the favorable safety profile and the oral route of administration, apremilast may represent a promising therapeutic target for moderate-to-severe psoriasis. In this review, we report an updated overview about clinical trials testing apremilast in the treatment of psoriasis and seek to provide comprehensive information about this anti-psoriatic drug and a future perspective of the therapeutic algorithm for psoriasis.

Usefulness of QuantiFERON®-TB Gold test in psoriatic patients under treatment with tumour necrosis factor blockers

Objective: Infliximab is a human/mouse chimeric anti-tumour necrosis factor (TNF)-α antibody that is effective in the management of psoriasis. Anti-TNF treatments may reactivate latent tuberculosis infection (LTBI); therefore, screening for LTBI is mandatory before starting any anti-TNF-α therapy. The aim of this study is to evaluate the usefulness of the QuantiFERON®-TB Gold (QFT-G) test in psoriatic patients under treatment with infliximab. Research design and methods: A retrospective study had been performed on patients affected by psoriasis who had been treated with infliximab from 2003 to 2012 at a single centre. Main outcomes measures: QFT-G was tested by a standard TB enzyme-linked immunosorbent assay, based on detection of interferon-γ release from sensitized leucocytes exposed to the synthetic Mycobacterium tuberculosis antigens at baseline and every 6 months until the end of treatment. Results: A total of 140 patients were included. At baseline, 7 QFT-G tests were positive and 133 tests were negative. Of the 133 patients, 11 (8%) who were negative at baseline became QFT-G test positive during treatment. Of those 11 patients, 5 had a reversion during treatment. Of the 133 patients, 122 (92%) who were negative at baseline remained negative. Conclusions: It was found that the development of positive QFT-G tests, observed in 8% treated with infliximab, was not associated with pulmonary or extra-pulmonary tuberculosis.