Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore.

Introduction: Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis. Methods: This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16. Results: A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years. Conclusion: Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)-mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.

Systematic review and practical guidance on the use of topical calcipotriol and topical calcipotriol with betamethasone dipropionate as long-term therapy for mild-to-moderate plaque psoriasis.

While many patients with psoriasis are candidates for topical agents, long-term treatment effects are unclear. This systematic review evaluated global findings from clinical trials and real-world studies of topical calcipotriol and the two-compound formulation of calcipotriol and betamethasone dipropionate for mild-to-moderate plaque psoriasis (including scalp psoriasis). PubMed, Embase and MEDLINE were searched for relevant English-language publications along with Chinese, Japanese, Korean and Latin American publication databases. Identified articles were screened by title and abstract against predefined inclusion/exclusion criteria. A narrative synthesis of key efficacy and safety findings from the full papers of selected publications was developed. Thirty-seven relevant papers were identified (25 English, 11 Chinese and one Japanese-language study) including 28 randomized controlled trials. While there was significant heterogeneity in study length, treatment intensity and clinical measures, following a critical review of the published data combined with expert opinion, the following clinical practice recommendations were agreed in order to assist healthcare providers: in adults, long-term treatment with calcipotriol/betamethasone dipropionate is well tolerated and efficacious for up to 1 year on an 'as needed' basis, and for up to 16 weeks on a fixed-treatment regimen. Calcipotriol is also well tolerated and efficacious when used long term (up to 52 weeks) 'as needed' and for up to 20 weeks on a fixed-treatment regimen. Used on an 'as needed' basis for up to 1 year, the safety and efficacy profile of fixed-dose combination calcipotriol/betamethasone dipropionate is more favorable than calcipotriol alone; regular consultation between patients and their dermatologist/primary care physician is required to review psoriasis symptoms and adjust treatment accordingly; a specific treatment goal should be agreed on initiation of topical agent(s) to determine when long-term treatment can begin or if a regimen change is warranted; and application frequency during the continued treatment phase should consider the patients' treatment expectations and goals.

Spotlight on Topical Long-Term Management of Plaque Psoriasis.

During the 28th Congress of the European Academy of Dermatology and Venereology (EADV) held in Madrid in October 2019, an industry hub was dedicated to the long-term management of psoriasis. Psoriasis is a systemic inflammatory disease primarily involving the skin that affects up to 4% of the European population, the majority of whom present with chronic plaque psoriasis. Topical therapies are well established in the first-line treatment of psoriatic plaque flares. Nevertheless, as psoriasis is a chronic disease, long-term control should be considered. The aim of the session was to provide expert opinion on the benefit of long-term maintenance therapy in chronic plaque psoriasis and introduce the concept of pro-active management to decrease the number of relapses and improve patient quality of life. The current guidelines and recommendations were reviewed, as well as the available data on published clinical trials. There is still an important role for topical therapy in psoriasis and current recommendations suggest a maintenance regimen for psoriasis. Adherence optimization and proactive management of relapse can be key factors for obtaining clinical outcomes in topical long-term therapy. Calcipotriol/betamethasone dipropionate foam is the only topical formulation with long-term data as a twice-weekly proactive treatment approach for up to 52 weeks for chronic plaque psoriasis.

Serum Adiponectin Levels and Their Association With Cardiometabolic Risk Factors in Patients With Psoriasis.

Background and objective Low adiponectin levels have been described in conditions with high cardiometabolic risk, including obesity, type 2 diabetes, insulin resistance, and hyperlipidaemia. Psoriasis is a chronic inflammatory skin disorder, and it is also associated with these conditions. In this study, we sought to assess the correlation between adiponectin levels and these risk factors including psoriasis severity. We investigated adiponectin value and its correlation with components of metabolic syndrome (MetS) and psoriasis severity. Methods Serum adiponectin levels were obtained from 215 psoriasis patients in a tertiary dermatology centre in Singapore. Psoriasis severity was measured with the psoriasis area and severity index (PASI), and cardiometabolic risk factors including obesity, hyperlipidaemia, insulin resistance, and waist circumference were measured. Patients answered a questionnaire regarding alcohol use, exercise, family history, smoking, and treatment history. Results Low adiponectin value was found in psoriasis patients with high body mass index (BMI) risk, high low-density lipoprotein (LDL), and low high-density lipoprotein (HDL). Patients with low HDL value had 25% lower adiponectin value compared to those with normal HDL. Adiponectin levels had a negative correlation with waist circumference. Psoriasis patients with MetS and a family history of cerebral vascular accidents (CVAs) had 17% and 18% lower adiponectin values than those without, respectively. There was no correlation between adiponectin level and PASI score. Conclusion Adiponectin levels were significantly decreased in psoriasis patients with obese-level BMI, MetS, increased abdominal girth, low HDL, high LDL, and a family history of CVA. Low adiponectin levels could play a role in predicting the development of MetS and possibly enable intervention to decrease the risk of cardiovascular mortality in psoriatic patients.

Clinical Goals and Barriers to Effective Psoriasis Care.

Engaging global key opinion leaders, the International Psoriasis Council (IPC) held a day-long roundtable discussion with the primary purpose to discuss the treatment goals of psoriasis patients and worldwide barriers to optimal care. Setting clear expectations might ultimately encourage undertreated psoriasis patients to seek care in an era in which great gains in therapeutic efficacy have been achieved. Here, we discuss the option for early treatment of all categories of psoriasis to alleviate disease impact while emphasizing the need for more focused attention for psoriasis patients with mild and moderate forms of this autoimmune disease. In addition, we encourage policy changes to keep pace with the innovative therapies and clinical science and highlight the demand for greater understanding of treatment barriers in resource-poor countries.

Asian consensus on assessment and management of mild to moderate plaque psoriasis with topical therapy.

A working group of dermatologists in Asian countries assessed the current status of psoriatic management in the region to prepare a consensus report on topical treatment in mild to moderate plaque psoriasis. Even though the association of psoriasis with systemic comorbidities is increasingly acknowledged, psoriasis is still lower in health-care priority lists in the region. The psychosocial impact of psoriasis may be greater in Asian countries due to cultural norms and social discrimination. Non-adherence to treatment is also common among Asians. The current care given to patients with mild to moderate psoriasis needs to be streamlined, enhanced and organized with a patient-centered care approach to achieve better outcomes. A comprehensive assessment of the disease severity and its impact on a patient's life is required before initiating treatment. Education and active involvement of the patient in the treatment plan is an important part of psoriatic management. It is recommended to personalize topical treatment to meet the needs of the patient, depending on disease severity, psychosocial impact, the patient's expectations and, more importantly, the patient's willingness and ability to actively follow the treatment procedure. Fixed-dose combination of corticosteroid and vitamin D analogs is the preferred topical medication for both initial and maintenance phases of treatment. The fast containment of the disease is the goal of the initial phase of 4-8 weeks and it demands a potent fast-acting topical therapy. Satisfactory control of the disease and prevention of relapses should be achieved during the maintenance phase with twice a week or weekend applications.

Photodynamic Therapy With Topical 5% 5-Aminolevulinic Acid for the Treatment of Truncal Acne in Asian Patients.

BACKGROUND: Photodynamic therapy (PDT) using topical application of aminolevulinic acid (ALA) is an effective treatment for acne vulgaris. However, there is no clear consensus on the treatment regime in Asians.
AIM: To determine the efficacy, safety and tolerability of 5% ALA PDT in the treatment of truncal acne in Asians.
METHODS: Patients with truncal acne were treated with 5%-ALA under occlusion for 3 hours. All were subsequently treated with a red light source at wavelength 630 nm and an irradiance of 38mW/cm2 giving a total dose of 37 J/cm2. The numbers of acne lesions were recorded at baseline and regular intervals after treatment together with any adverse effects.
RESULTS: Fifteen patients were recruited. Overall, there was a 64.2% reduction in the inflammatory lesions count and a 24.3% reduction in the non-inflammatory lesions count at the end of the 12 weeks follow-up. Both mean lesions counts were significantly lower than baseline at all follow-up time points with paired t tests (all P values <0.05). Pain was well tolerated among our patients.
CONCLUSION: A single treatment session of 5%-ALA PDT was effective for the treatment of truncal acne with little side effects and acceptable in our Asian patients.

J Drugs Dermatol. 2016;15(6):727-732.

The MARCOPOLO Study of Ustekinumab Utilization and Efficacy in a Real-World Setting: Treatment of Patients with Plaque Psoriasis in Asia-Pacific Countries.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody approved for the treatment of chronic moderate-to-severe plaque psoriasis in adults. However, factors including efficacy, tolerability, ease of use, and cost burden may affect ustekinumab utilization. Noncompliance may, in turn, affect treatment response. OBJECTIVE: To evaluate ustekinumab utilization in the real-world setting in Asia-Pacific countries. METHODS: In this phase 4 observational study conducted in Indonesia, Malaysia, Singapore, Korea, and Taiwan, adults with plaque psoriasis receiving ustekinumab were followed for up to 52 weeks. Study endpoints were the proportion of all patients using ustekinumab according to label-recommended intervals and the proportion of Korean patients who achieved a psoriasis area severity index 75 response at week 16. Safety was assessed by monitoring adverse events. RESULTS: Overall, 169 patients received ustekinumab (Korea, n=102; other countries, n=67). Just over half (56.2%) of patients used ustekinumab with the label-recommended interval from baseline to week 40; the proportion was higher in Korea (73.5%) than in other countries (29.9%), probably because ustekinumab was provided without charge for Korean patients up to week 40. Noncompliance increased after week 40 in Korea and from week 28 in other Asia-Pacific countries, with cost cited as the most common reason. At week 16, 56.9% of Korean patients achieved a Psoriasis Area Severity Index 75 response. Safety results were in line with those seen in previous studies. CONCLUSION: More than half of all patients in Asia-Pacific countries used ustekinumab as per the label-recommended dose interval, but reimbursement variations between countries may have confounded overall results.

Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

Use of an Interferon-γ Release Assay in the Detection of Latent Tuberculosis in Dermatology: A Descriptive Analysis.

With the increasing use of biologic therapy in psoriasis, it is becoming more important to identify and treat latent tuberculosis (TB) infection (LTBI). Tuberculin skin test (TST) has been traditionally used to detect LTBI, but interferon-γ release assays (IGRAs), such as the T-SPOT.TB test (T-Spot), are increasingly being used in its place. The indications and results of 51 T-Spot tests performed at the National Skin Centre in Singapore between 2008 and 2010 were analyzed and compared with TST results, decision on LTBI treatment, and previous use of immunosuppressants. T-Spot was most commonly performed as part of a prebiologic workup in patients with psoriasis. A total of 14 (27.5%) results were positive, and no patients had features of active TB. Ten of these patients also underwent TST, five of whom had negative TST results. Six patients (11.8%) had equivocal results with T-Spot test. This study shows poor concordance between T-Spot test and TST. A high incidence of equivocal results in IGRA may limit the utility of the T-Spot test.

Association between psoriasis and leisure-time physical activity: findings from the National Health and Nutrition Examination Survey.

Despite evidence that physical activity can reduce the cardiometabolic risk of patients with psoriasis, these patients may engage in less physical activity than those without psoriasis. The aim of this study was to examine the association of the extent of psoriatic skin lesions with the likelihood of participating in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET)-minutes of MVPA amongst those who participated. The National Health and Nutrition Examination Survey (NHANES) is a population-based survey among U.S. adults. A total of 6549 persons aged 20-59 years responded to the 2003-2006 NHANES dermatology questionnaires, which asked about participation in leisure-time MVPA and MET-minutes of MVPA amongst those who participated. Compared with individuals without psoriasis, those with psoriasis were less likely to have engaged in leisure MVPA in the past 30 days, although this association was not statistically significant. Amongst those who participated in leisure-time MVPA, MET-minutes of leisure-time MVPA were lower on average for patients currently having few to extensive cutaneous lesions (but not for those currently having little or no psoriatic patches), relative to individuals never diagnosed with psoriasis by approximately 30%. Clinicians should encourage patients with psoriasis, especially those with more severe disease, to be more physically active; they should help identify and address possible psychological and physical barriers to their patients' physical activity.

Clinical characteristics of adult-onset actinic prurigo in Asians: a case series.

BACKGROUND: Actinic prurigo (AP) is a chronic, pruritic skin condition caused by an abnormal reaction to sunlight. AIMS: The aim of this study is to determine the clinical characteristics of AP in patients attending the National Skin Centre, Singapore, from 1 st January 1999 to 30 th June 2008. METHODS: Cases of AP diagnosed from 1 st January 1999 to 30 th June 2008 were retrieved from the center's electronic medical records and analyzed. RESULTS: A total of 11 patients were diagnosed with AP. The mean age at diagnosis was 52 years. There were 9 (82%) Chinese and 2 (18%) Malay patients. Nine (82%) were male and 2 (18%) were female. The most commonly affected areas were the face, forearms, and hands (72%). Phototesting showed reduced minimal erythema dose (MED) to ultraviolet A (UVA) in 5 (46%) patients, both UVA and ultraviolet B (UVB) in 4 (36%) patients and UVB in 1 (9%) patient. Seven (64%) patients reported partial improvement after treatment with a combination of topical corticosteroids and sunscreens. Four (36%) patients received systemic therapy with partial response. CONCLUSION: Adult-onset AP is more common in the Asian population, with a male predominance. The face, forearms, and hands are the most commonly affected areas. The absence of mucosal involvement is also a distinguishing feature between the Asian and Caucasian population. Close to half of the patients have reduced MED to UVA on phototesting. The prognosis for AP is poor as it tends to run a chronic course with suboptimal response to treatment.

Photopatch testing in Asians: a 5-year experience in Singapore.

BACKGROUND: Photopatch testing is important for diagnosing photoallergic contact dermatitis. We aimed to evaluate the use of photopatch test at the National Skin Centre, Singapore. METHODS: All patients who had photopatch tests done between 2007 and 2011 at the National Skin Centre were included. RESULTS: Twenty-two patients were included. The mean age was 40.2. Female : male ratio was 3.4. The ethnic groups were Chinese (68%), Malay (4%), Indian (14%) and others (14%). Ten out of 22 patients (45.5%) had a positive photopatch test. There were 20 positive photopatch test reactions found in these 10 patients, and all 20 positive reactions were of current relevance. The frequencies of the positive photopatch test reactions were 2-hydroxy-4-methoxybenzophenone (oxybenzone) (n = 6), 2-hydroxymethoxymethylbenzophenone (mexenone) (n = 3), 2-ethylhexyl-4-dimethylaminobenzoate (n = 1), ketoprofen gel (n = 1) and the patient's own product (n = 9). CONCLUSIONS: Our study suggests that sunscreen is the most common photoallergen to date as opposed to musk ambrette, which was the most common photoallergen in our earlier study in 1991-1993. This finding is similar to the recent European Multicentre Photopatch Test Study.

Genetic study in a Singaporean patient with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haem biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity which leads to the excessive accumulation of protoporphyrin in blood, erythrocytes and tissues. Cutaneous manifestations of photosensitivity usually appear in early infancy upon the first sun exposures. This normally requires the co-inheritance of a common hypomorphic FECH allele and a deleterious FECH mutation. Here, we report the first Singaporean Chinese patient with EPP characterized at the molecular level.

Chronic actinic dermatitis in Asian skin: a Singaporean experience.

BACKGROUND/PURPOSE: To study the characteristics of chronic actinic dermatitis (CAD) in a heterogeneous group of Singaporean patients. METHODS: The photobiologicial features of all patients phototested and diagnosed with CAD from January 2005 to December 2009 were examined retrospectively. RESULTS: Fifty-eight patients were diagnosed as having CAD. The mean age at diagnosis was 62 years (range 35-83). Forty-one were (70.7%) Chinese, six (10.3%) Indians, eight (13.8%) Malays, and three (5.2%) Others. Forty-seven were (81.0%) male and 11 (19.0%) were female. Forty-nine (84.5%) had Fitzpatrick skin phototype IV and nine (15.5%) had phototype V. Three of 26 (11.5%) tested for human immunodeficiency virus were positive. The face, neck, and forearms were most commonly affected. Thirty-two patients (55.2%) had reduced minimal erythema dose (MED) to both ultraviolet B (UVB)and ultraviolet A (UVA), 23 patients (39.7%) had lowered MED to UVB only, while three (5.1%) had reduced MED to UVA only. Patients were followed up for a mean of 16.8 months. All were treated with photoprotection and topical steroids; however, a few required oral immunosuppression with partial improvement. CONCLUSION: In Singapore, CAD was seen more commonly in elderly Chinese males of Fitzpatrick skin phototype IV. Reduced MED to both UVB and UVA was the most common phototest finding.

Narrowband UVB-induced lichen planus pemphigoide.

Lichen planus pemphigoides (LPP) is an autoimmune disease characterised by evolution of subepidermal blisters on normal and lichen planus affected skin. We describe a case of LPP in a 54-year-old Chinese woman. The patient presented with psoriasiform plaques and was diagnosed with guttate psoriasis. Narrowband ultraviolet B (NBUVB) therapy was commenced, and she experienced a generalised eruption of violaceous papules, bullae over the lower limbs, and Wickham's striae over the buccal mucosa. Histology from a plaque revealed interface dermatitis, while a specimen from a blister showed subepidermal bulla. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane. A diagnosis of LPP was made on clinicopathological grounds. This is the first case report of NBUVB alone in unmasking LPP. In this case report, we describe the pathological mechanism of NBUVB in the development of LPP and key features distinguishing LPP from bullous lupus erythematosus, bullous lichen planus, bullous pemphigoid, and psoriasis.