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Background: Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. Objectives: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. Methods: This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs). Results: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100-treated patients with MetS, 98 and 167 TIL100-treated patients without MetS, 34 and 30 TIL200-treated patients with MetS, and 111 and 130 TIL200-treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100-treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200-treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. Conclusions: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

With the rapid development of new, targeted therapies for the treatment of moderate/severe atopic dermatitis, it is opportune to review the available conventional systemic agents. We assess the published evidence for systemic therapies for atopic dermatitis and amalgamate this with real-world experience. Discussions are centred on when systemic therapy should be considered, which drug(s), what dose, how to sequence or combine these therapies, how long they should be continued for and what is considered success.

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) has significant negative impact on health-related quality of life, mood, sleep, work productivity and everyday activities. Research into the use of new drugs in the management of AD continues to develop, and international updates and recommendations have been published. However, questions remain in the Australian setting. This consensus aims to provide evidence-based insights and practical advice on the management of adult AD in Australia. METHODS: A panel (five dermatologists and one clinical immunologist) met to review the literature, critically examine clinical questions of relevance to Australian healthcare practitioners and develop a series of recommendation statements. A consensus panel, comprising the initial panel plus nine additional members, used a 2-round Delphi voting process to determine a set of final guidance statements. CONSENSUS: ≥75% agreement in the range 7-9. RESULTS: Round 1 voting comprised 66 guidance statements. Of these, consensus was reached on 26, which were retained, and five were removed. The remainder (35) were modified and one new guidance statement was added for inclusion in round 2 voting. After round 2, consensus was reached on 35, which were retained, and one was removed (considered redundant). The 61 guidance statements upon which consensus was reached were then used to support a series of core consensus recommendations and a management flow chart. CONCLUSIONS: Expert consensus recommendations providing practical guidance of clinical relevance to specialists and primary care physicians in Australia have been developed. Dissemination of this guidance and evaluation of its impact on patient outcomes remain to be undertaken.

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics.

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle-aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.

Background Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. Objectives To evaluate dosing frequency response of imiquimod 5% for treatment of AK. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with >= 10 but <= 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. Results One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (>= 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. Conclusions Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002). © 2009 British Association of Dermatologists.