John Sullivan

Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from GESTURE, a randomized controlled trial

Background: Plaque psoriasis affecting palms and soles is disabling and often resistant to treatment. Objective: Evaluate the efficacy and safety of secukinumab, an anti‐interleukin 17A antibody, in subjects with palmoplantar psoriasis. Methods: In this double‐blinded, randomized controlled trial, 205 subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The primary endpoint was Palmoplantar Investigators Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16. Results: At week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the percentage achieved with placebo (1.5%, P < .001). Palmoplantar Psoriasis Area and Severity Index (ppPASI) was significantly reduced with secukinumab 300 mg (−54.5%) and 150 mg (−35.3%) compared with placebo (−4.0%, P < .001). Dermatology Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups were also significantly higher compared with placebo at week 16 (P < .01) and pain and function of palms and soles was markedly improved with secukinumab as measured by the palmoplantar Quality‐of‐Life Instrument. Secukinumab 300 mg consistently showed the best outcomes. The safety profile was favorable and similar to previous studies. Limitations: Lack of active comparator. Conclusion: In GESTURE, the largest randomized controlled trial in palmoplantar psoriasis, secukinumab demonstrated the greatest efficacy to date for treating difficult‐to‐treat psoriasis.

Vitamin A deficiency phrynoderma: Due to malabsorption and inadequate diet

We describe a patient with vitamin A deficiency phrynoderma caused by a combination of inadequate dietary intake of vitamin A and beta-carotene and malabsorption secondary to primary visceral myopathy and total colectomy.

Psoriasis in those planning a family, pregnant or breast‐feeding. The Australasian Psoriasis Collaboration

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 view on methotrexate for psoriasis in the Australasian setting.

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.

High Patient Satisfaction with Daylight-Activated Methyl Aminolevulinate Cream in the Treatment of Multiple Actinic Keratoses: Results of an Observational Study in Australia

IntroductionActinic keratoses (AK) are treated to reduce the risk of progression to squamous cell carcinoma and for symptomatic and cosmetic benefits. The objective of this observational study was to generate real-life data on the use of daylight photodynamic therapy with methyl aminolevulinate cream (MAL DL-PDT) in treating mild to moderate facial/scalp AK.MethodsA multicenter, prospective, observational study was conducted in Australia in patients receiving a single treatment of MAL DL-PDT for mild to moderate AK. Efficacy was assessed 3xa0months after treatment by investigator-assessed improvement and patient- and physician-completed satisfaction questionnaires. Adverse events were recorded throughout the study.ResultsOverall, 81 patients were enrolled of mean age 62.7xa0years, mostly men (76.5%) with skin phototype I (64.2%) or II (35.8%) and a long history of AK (mean duration 16.8xa0years). Most had multiple lesions (82.7% had >10 lesions) of predominantly grade I (75.3%). At 3xa0months after treatment, almost half the patients (46.8%) required no further treatment. The proportions of patients and physicians satisfied to very satisfied with the MAL DL-PDT treatment were 79.7% and 83.3%, respectively. After receiving the treatment, 74.1% of patients indicated via the questionnaire that they were not bothered at all by the pain. Related AEs were reported in 48.1% of patients, mainly mild erythema (44.4%).ConclusionsIn clinical practice in Australia, the use of MAL DL-PDT in treating multiple mild to moderate non-hyperkeratotic AK of the face and/or scalp results in high levels of patient and physician satisfaction reflecting the good efficacy and tolerability of this almost painless, convenient procedure.Trial RegistrationClinicalTrials.gov identifier, NCT02674048.FundingGalderma R&D.

Ixekizumab efficacy and safety in moderate-to-severe genital psoriasis

Psoriasis is a common skin disease that affects about 2% of people worldwide. It presents with red, scaly, and often itchy patches that can affect skin anywhere on the body. About 63% of patients have psoriasis in the genital region at some point in the course of their disease. Genital psoriasis is difficult to treat and it can be a particularly painful, itchy, uncomfortable, and embarrassing form of psoriasis. It also leads to difficulties in personal relationships, sexual health, and overall quality of life. This study aimed to determine whether ixekizumab, a drug used to treat overall psoriasis, also successfully treats genital psoriasis. Patients with genital psoriasis from multiple global countries were treated with either ixekizumab or a placebo (a dummy injection lacking an active drug). The effect of ixekizumab was compared to placebo over 12 weeks of treatment using a combination of clinical tools to measure genital psoriasis severity as well as patient‐completed questionnaires about the impact of their genital psoriasis on their quality of life and sexual health. Ixekizumab provided greater improvements in genital psoriasis severity, with over 73% of patients having minimal or no genital psoriasis and 56% having no genital psoriasis at Week 12. The effect of ixekizumab was rapid, with clear improvements observed as early as the first week of treatment. Rapid and greater improvements were also seen in the severity of genital itching and the impact of genital psoriasis on the frequency of sexual activity. This study suggests that ixekizumab is an effective treatment for genital psoriasis.

Psoriasis and infection. A clinical practice narrative

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including β‐haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune‐modulatory treatments. The decision whether to, and when to, stop or resume immune‐modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune‐modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low‐risk surgical procedures. For moderate‐ and high‐risk surgeries, a case‐by‐case approach should be taken based on the patients individual risk factors and comorbidities.

Psoriasis and cancer. An Australian/New Zealand narrative

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.