treatment of psoriasis

Psoriasis is a disease of great importance because it affects 2%–3% of the Western population, is associated with sev- eral severe comorbidities, and is associated with impaired quality of life and a shortened lifespan in patients with severe disease. Brodalumab, secukinumab, and ixekizumab represent a new frontier in our therapeutic strategy for the treatment of psoriasis. The significant clinical responses seen in patients diagnosed with psoriasis following block- ade of either the ligand IL-17A or its receptor confirm the hypothesis that IL-17 signaling has a critical role in this immune-mediated disease. So far, the results of clinical tri- als on brodalumab, secukinumab, and ixekizumab indicate that the three drugs are more or less equally efficient when the therapeutic agent is given at the right dose and in the right regimen. PASI 75 is the most frequently used measure- ment to evaluate drug efficiency in clinical trials on plaque psoriasis; however, since the therapeutic agents have very high efficiency, the PASI 90 response could be the primary endpoint in future. The goal for patients is usually complete remission of their skin disease; it is therefore beneficial – both for the patients and for evaluation of the therapeutic agent – to use PASI 90.

Methotrexate has been since long time used for treatment of psoriasis as an effective therapy. It is a potent competitive antagonist of the enzyme dihydrofo- late reductase; this leads to inhibition of DNA synthesis at the S phase. It was approved by the FDA for the treatment of psoriasis since 1971. Jeffes and col- leagues [4] demonstrated in an in vitro experiment that the effect of MTX on the proliferation of lymphoid cells is 1000 times greater than its effect on human keratinocytes. Thus, at concentrations reached in vivo , it is most likely that MTX acts via an immunosuppressive mechanism, rather than as an antiproliferative agent directed against the keratinocyte. Sigmundsdottir and colleagues [5] have demonstrated depression of cutaneous lymphocyte-associated antigen-positive T cells and endothelial E-selectin in MTX-treated psoriatic patients. Methotrexate can be administered orally, IV, IM and SC, with the oral route providing the most reliable blood level [6].

Background: With a growing number of psoriasis treatments options, making a decision can be daunting to patients. Biologics offer a less toxic and more effective alternative to people who have moderate-to-severe psoriasis, particularly those who have tried and failed other therapies. Objective: To provide a patient-centered approach to the decision to start on biologic treatment of psoriasis with an overview of pharmacology. Methods: An electronic literature search was performed in the PubMed and Medline databases using keywords with "biologics" or "biologic therapy,” “treatment,” and “safety.” Pharmaceutical package inserts and reference lists were also reviewed. Results: Though new advancements in psoriasis care have improved treatment options for patients, widespread treatment dissatisfaction and under- treatment occurs. Biologic agents are generally well-tolerated and effective for managing moderate-to-severe psoriasis. Lifetime risks of serious adverse events from biologic treatment are less than risks patients face on a daily basis. Current data suggests biologics are not predictors of serious adverse events. Rates of major adverse cardiovascular event and death are lower in biologic cohorts compared to non-biologic cohorts. The minimal risk and potentially protective effects of biologics may outweigh the consequences of undertreated or non-treated moderate-to-severe psoriasis. Limitations: Long-term data on biologic treatment safety is growing and this review will only encompass current data. Conclusions: Treating psoriasis with biologics can reduce overall risk of bad outcomes of psoriasis and its treatment and improve patient quality of life. Optimizing treatment adherence, accommodating patient preferences, emphasizing strong patient-physician communication, and conceptualizing treatment risk can improve patient satisfaction and clinical outcomes. Successful psoriasis care is a long-term, collaborative, and complete commitment on behalf of both the patient and physician. Journal of Nature and Science, 1(3):e53, 2015.

Abstract: Elucidation of the immunopathogenesis of psoriasis has led to the discovery of novel biologic agents for the treatment of moderate-to-severe plaque psoriasis. There are currently five biologic agents approved by the US Food and Drug Administration for psoriasis which have proven to be quite efficacious in clinical trials and in post-marketing and clinical experience. As more details are uncovered about the immunologic pathways involved in initiation and maintenance of this disease, there will be an increasing development and marketing of novel therapeutics. It is crucial to understand the immunopathogenesis of psoriasis and the mechanisms of these novel agents in order to to treat the psoriatic population effectively and mitigate disease burden. This article reviews the currently approved biologics for the treatment of psoriasis, with emphasis on efficacy and safety. There are countless therapies currently in the research pipeline, with mechanisms ranging from receptor antagonism to signal transduction pathway inhibition. The initial trials and future studies involving these new agents are also reviewed. As therapeutics escalate through the research pipeline, the management and treatment of psoriasis will likely become more manageable for practitioners and patients.

Abstract: Psoriasis is a chronic immune-mediated systemic disease that is influenced by genetic and environmental factors, is associated with comorbidities, and has a negative impact on the quality of life of affected individuals. The prevalence of psoriasis varies among different ethnic groups, but this topic has not been studied in Brazil to date. In this review, we evaluate the epi- demiology and treatment of psoriasis from a Brazilian perspective. We focused on studies that involved Brazilian subjects. The prevalence of psoriasis in Brazil is estimated to be 2.5%, but no population study has been performed previously. Environmental factors, such as tropical climate, in association with genetic factors, such as miscegenation, may exert a beneficial impact on the course and frequency of psoriasis in Brazil. A number of studies have advanced our understand- ing of the cardiovascular, ophthalmic, and oral comorbidities that are associated with psoriasis. Concerns about biological therapy, such as endemic leprosy, human T-cell lymphotropic virus (HTLV), and tuberculosis infections, are discussed. The nonavailability of treatment options for psoriasis in the public health system contradicts the Brazilian Society of Dermatology guidelines, stimulating the judicialization of access to medicines in psoriasis care.

Topical agents are fundamental in the treatment of psoriasis. They target the affected skin directly and have the advantage of being effective, safe, and well tolerated. Mild disease can be successfully treated by topical treatment alone, while moderate and severe disease can be controlled with com- bined phototherapy or/and systemic therapy. Since topical treatments often require long-term use, it is suggested that patients receive an individualized treatment that is adjusted over time as required. Type of topical agent should be considered. Creams and ointments are the most common formulations for epidermal psoriasis. Solutions and lotions are regularly used for scalp psoriasis. For very thick lesions, short-term plaster or occlusive treatment is often used. In the People’s Republic of China, most psoriasis patients are classified as mild to moderate severity. As such, topical treatment is most often used; topical corticosteroid is the most frequently prescribed medication for psoriasis patients. Topical vitamin D analogs, retinoids, and tacrolimus oint- ment are also frequently used.

Abstract: Biologics are novel and important agents in the treatment of severe psoriasis. These agents block specific molecular steps in the inflammatory cascade, thereby reducing activation and proliferation of keratinocytes. Prescreening for biologic agents and careful monitoring of patients is important. There are four biologics currently licensed and used in the treatment of psoriasis in the European Union. This is an evidence-based review examining clinical trials and focusing on the long-term safety data for four biologic agents. Current British Association of Dermatology guidance for the use of biologics in psoriasis and guidelines on the management of psoriasis from the National Institute for Health and Clinical Excellence have been used. Advances on safety information since 2009 in clinical trials are reviewed. The results show that overall there is no statistical significance in the incidence of adverse effects of biologics versus placebo. However, there are serious adverse effects that are reported for biologics that need to be assessed for and addressed promptly. Results of studies discussing major adverse cardiovascular events are also reviewed.

Various forms of psoriasis exist. Some can occur independently or at the same time as other variants, or one may follow another. Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches covered by a silvery, flaky surface. The primary disease activity leading to psoriasis occurs in the epidermis (a hyper proliferative skin disease with a markedly increased 5-6 times normal rate of epidermal turnover).The process starts in the basal (bottom) layer of the epidermis. Here, Keratinocytes are immature skin cells that produce keratin, a tough protein that helps to form hair and nails as well as skin. In normal cell growth, keratinocytes mature and migrate from the bottom (basal) layer to the surface and are shed unobtrusively. This process takes about a month. In psoriasis, however, the keratinocytes proliferate very rapidly and travel from the basal layer to the surface in only about four days. The skin cannot shed these cells quickly enough so they accumulate in thick, dry patches, or plaques. Silvery, flaky areas of dead skin build up on the surface of the plaques and are shed. The underlying skin layer, the dermis, is red and inflamed. The dermis contains nerves and blood and lymphatic vessels, which supply the abnormally multiplying keratinocytes with their blood supply and also transport potent immune factors that cause the underlying inflammation and redness [1-2].

The major concern for validation is the lack of quality control and insufficient statistical analysis, so there is a need for standards to develop validation criteria for biomarker selection. Here we review the data from several studies on some of the most valuable candidate biomarkers for cutane- ous psoriasis and psoriatic arthritis, detection of systemic inflammation, and assessment of the therapeutic outcome. We focus our attention on the molecules that take part in the complex interplay giving rise to psoriasis and on the gene products that may represent a link between predisposing genetic factors and the immune and inflammatory processes involved in the pathogenesis of the disease (Figure 1). Finally, we provide an overview on how biomarkers can provide insights into the pathogenesis of psoriasis.

Both rheumatology studies have shown significantly higher ACR20 responses for each dose of tofacitinib compared to placebo at month 3. Improvements in both trials were observed with tofacitinib as early as week 2. Patients in OPAL Beyond had failed one or more TNF inhibitors, implying that they had disease which was resistant to treatment, and yet 50-60% had an ACR20 response to treatment with tofacitinib by the end of the study. Both studies used the ACR composite measure, which is validated for rheumatoid arthritis but not PsA. It could also be argued that ACR20 as a primary endpoint is a relatively low target to assess for efficacy. The higher targets of ACR50 and ACR70 were achieved apart from ACR70 in the OPAL Beyond study. When composite endpoint measures of disease specific for PsA (such as the Psoriatic Arthritis Disease Activity Score and Composite Psoriatic Disease Activity Score) are applied to the results of the OPAL trials both doses of tofacitinib showed improvements compared with placebo at 3 months [29]. This demonstrates that tofacitinib improves measures that assess across all domains of PsA.

As mentioned before, secukinumab’s main route of elimi- nation is via intracellular catabolism and thus the potential for drug interactions between secukinumab and small drug molecules is low. In addition, cytochrome P450 enzyme inhibitors and inducers are unlikely to affect the secuki- numab exposure–response relationships, given that hepatic metabolizing enzymes, such as cytochrome P450 and uridine 5 ′ -diphospho-glucuronosyltransferases (UGTs), are not presumed to be involved with monoclonal antibody elimination. Other monoclonal antibodies used in treating psoriasis, including infliximab and adalimumab, have been noted to have decreased clearances when administered with methotrexate. However, PK results in a dose-finding study with secukinumab in rheumatoid arthritis patients indicated that methotrexate does not have an impact on the disposition of secukinumab. 18,19

Up to 40% of psoriasis patients have or will develop psoriatic arthritis during their lifetimes, so treatment of joint symptoms in addition to skin symptoms is critical to prevent irreversible joint damage. Secukinumab is one of six biologics currently approved for the treatment of both psoriatic arthritis and psoriasis vulgaris, a group that also includes etanercept, adalimumab, infliximab, ustekinumab, and ixekizumab. Secukinumab results in excellent ACR response after 24 weeks of treatment, but this biologic also inhibits radio- graphic joint damage in psoriatic arthritis patients for up to 2 years. 29 Thus, secukinumab offers a long-term treatment

1,25-dixydroxyvitamin D 3 , binds to the vitamin D receptor and act as a heterodimer with the retinoid X receptor (RXR) (Bury et al 2001). Vitamin D receptors are present on keratinocytes and lymphocytes. The epidermal hyperproliferation, abnormal keratinization, and angiogenesis seen in psoriasis are normalized with vitamin D analogs; apoptosis is induced in infl ammatory cells and there is a switch from Th1 cytokines to Th2 cytokines (van de Kerkhof 1995, 1998; Barna et al 1997). To be more specifi c, calcipotriol can modulate the infl ammatory process in psoriasis by decreasing the levels of interleukin-1 (IL-1) (Muller et al 1988) and IL-6 (Muller et al 1991) and by reducing the CD45RO and C8 + T cells. Morover, it increases the levels of transforming growth factor- β 1 (TGF- β 1) and - β 2, which inhibit the epithelial cell growth (Koli and Keski-Oja 1993). Calcipotriol is sensitive to oxidizing agents and acidic residues; it reacts with alcohols, and easily undergoes epimerisation processes (Charakida et al 2006). Twice-daily calcipotriol has an excellent safety profi le (Cullen 1996) and is more effi cacious than short-contact anthralin (Berth-Jones et al 1992), tar (Tham et al 1994), fl uocinonide ointment (Bruce et al 1994) and is at least as effi cacious as betamethasone 17-valerate 0.1% ointment (Kragballe et al 1991; Cunliffe et al 1992). Despite its side- effect of local irritation, calcipotriol is not associated with the cutaneous atrophy of topical corticosteroids or messiness of tar and anthralin.

periods of time because o f the deficient lymphocyte-mediated response in the animal. Flaky skin (fsn) is an autosomal recessive mouse mutation with papulosquamous disease features similar to psoriasis. The fsn gene was discovered by the Jackson Laboratory research group (Bar Harbor, Maine U.S.A.) in 1985 (Sundberg et al, 1994). In fsn skin there is marked acanthosis, hyperkeratosis with focal parakeratosis, subcorneal pustules, dermal capillary dilation and a marked diffuse dermal infiltration of mixed inflammatory cells such as lymphocytes. The histological phenotype o f the donor was maintained in the skin graft for up to ten weeks, the symptoms primarily being epidermal proliferation and dermal inflammation. The flaky skin mouse mutation is a potentially useful animal model that will serve as an important tool to unravel the mechanisms behind the diseases such as psoriasis and in testing for anti-psoriatic compounds. As yet, there have been no published studies of the value o f this model and the testing o f anti-psoriatic compounds (Sundberg e/a/, 1994; Lowe, 1988).

consulting practicing dermatologists. Physicians were identified from the public lists of health care professionals and were screened for eligibility based on the criteria of whether they were licensed physicians between 1970 and 2006, specialized in dermatology, and actively managing ten or more psoriasis patients per month. Each physician was asked to recruit 8–10 consecutive patients presenting with psoriasis in his/her office. One hundred and forty-three phy- sicians were recruited from France and 61 physicians were recruited from both Spain and the UK (n = 265) to complete a detailed patient record form for patients presenting with psoriasis and receiving a prescription for topical agents, phototherapy, or systemic treatment during routine visits in the calendar year 2007. Patients who were 18 years or older and diagnosed as having psoriasis were recruited. Patients who had a missing value for age or gender were excluded from the data analysis.

pathogenesis of psoriasis is multifactorial with the immune system, environmental factors, and genetics all playing major roles. Variants in the genes encoding the IL-23 receptor and the IL-23 p19 subunit (IL-23A) have been shown to be associated with potential for developing plaque psoriasis. 1,5–7 IL-23 functions by triggering the dif-

Abstract: The treatment of psoriasis has evolved over the years, with the recent focus largely on the use of biologics and anti-interleukin-17 agents. With treatment options expanding, practitioners and patients may find control of psoriasis more convenient and safer to achieve. In this article, we review the literature on emerging medications for the treatment of psoriasis. Although some of the new medications under development, such as the anti-interleukin-17 agents, are being shown to be very efficacious in the treatment of psoriasis in premarketing tri- als, more information regarding their long-term use is needed to demonstrate their superiority over available modalities.

Vitamin D has gained attention in the past decade with more and more studies demonstrating the varied functions of vitamin D in the body other than its established role in bone and mineral metabolism. In the context of psoriasis, it has been used as topical formulations (calcipotriol, calcitriol and tacalcitol) for the treatment of psoriasis either as monotherapy or in combination with topical steroids.(5) Vitamin D is now known to influence the immunological function of dendritic cells as well as T cells, which are the key players in the pathogenesis of psoriasis.(6,7) Through vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 is shown to inhibit the proliferation of cultured human keratinocytes and to induce terminal differentiation of these keratinocytes.(8) Certain types of VDR gene polymorphisms have been found to be associated with psoriasis.(9) There are recent studies showing increased prevalence of vitamin D deficiency in patients with psoriasis when compared to control groups.(10–13)

Mandibular osteomyelitis in a patient with psoriasis is an uncommonly clinical manifestation while there is an increasing number of reports and studies on involvements of stomatology in psoriasis, especially the death of a patient via or not via Allogeneic bone marrow transplantation has never been reported. To review the management and possible mechanisms in pathogenesis and treatment of psoriasis, as well as the relative involvements between stomatology and psoriasis the typical case with pictures and files is reviewed and literature is collected.Wekeepthe knowledge that psoriasis is either a primary keratinocyte disorder or an immunocyte-mediated chronic skin inflammatory disease while bone marrow is under suspected for immunopathogenesis. More association of stomatologic conditions with psoriasis is emerging. Conclusively, allogeneic BMT and new knowledge are worth to be stressed by both stomatological and dermatological doctors. Further insights of this kind of auto immunologic disease are under its developing.

Abstract: Psoriasis is a chronic inflammatory disease estimated to affect 1%–3% of the worldwide population. It is not simply a cutaneous disease but also poses a significant medical, social, and economic burden worldwide. Tumor necrosis factor (TNF)-α inhibitors are currently amongst the most important drugs in the therapeutic management of psoriasis. Patients using TNF-α inhibitors are at risk for infections including active and latent tuberculosis. Adalimumab, one of the TNF-α inhibitors, is a fully human monoclonal antibody that received approval for the treatment of chronic plaque psoriasis in 2008. Its use has been studied extensively for its safety and efficacy profile in the clinical setting. For the purpose of this review, we accessed the major publications in English relating to the use of adalimumab for psoriasis. Adalimumab appears to be one of the most efficacious biologic agents for the treatment of psoriasis. Results from various clinical trials including the REVEAL, CHAMPION, and BELIEVE are included in this review. The most recent data from an ongoing post-marketing study (ESPRIT) is also included in the analysis. Research regarding the safety, efficacy, and patient-reported outcomes support a favorable risk-benefit profile for adalimumab.