Biological Therapy Interruption and Re-Treatment in Chronic Plaque Psoriasis.

While biological treatments for chronic plaque psoriasis should be administered continuously to maximize and maintain efficacy, interruptions in therapy may be necessary for a number of reasons. We reviewed the evidence from clinical trials on efficacy, safety and immunogenicity in clinical trials for approved biologic agents for chronic plaque psoriasis. A systematic search of three major medical databases was performed and a total of 35 articles were included into the analysis, including 13 controlled trials. Trials assessing continuous therapy against dosing as-needed therapy (including infliximab, etanercept and secukinumab) have demonstrated superior efficacy for continuous regimes. However, randomized withdrawal trials for etanercept, adalimumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab, showed no significant impact on skin clearance rates in patients who are interrupted once and then re-treated. With the possible exception of infliximab, temporary interruption in biologic therapy appears to be safe and most agents will regain efficacy after re-introduction. J Drugs Dermatol. 2021;20(10):1063-1071. doi:10.36849/JDD.5716.

Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital.

Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow-band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy.

Treatment modalities and risk of adverse events associated with biologic therapy: A 10-year observational review of the Australasian Psoriasis Registry.

BACKGROUND: Psoriasis is a chronic inflammatory disease affecting ~2-3% of the Australasian population. Therapeutic options include topical agents, phototherapy, systemic immunomodulators and biologic agents. Biologics present an acceptable short- and medium-term safety profile, derived mainly from randomised controlled trials (RCTs) and, however, may not represent real-world rates of adverse events (AEs). METHODS: A retrospective, observational study of patients enrolled in The Australasian Psoriasis Registry from April 2008 to October 2018 was conducted. Data were collected from 104 sites in Australia and New Zealand. Patient characteristics, treatments and AE data were collected. AEs were classified by MedDRA System events. RESULTS: 2094 patients were included (3765 patient-treatments), comprising; 1110 phototherapy, 1280 systemic and 1375 biologic therapy patient-treatments. Treatment arms were not mutually exclusive. The mean ± SD from date of diagnosis of psoriasis to commencement of biologic therapy was 8.9 ± 12.3 years. Methotrexate had the longest exposure time (3740.3 patient-years), and ustekinumab had the longest median (95% CI) time on treatment, 4.3 years (2.2, 6.6). AE differences on biologic treatment were present between patients who would have been eligible or ineligible for RCTs. Approximately 29% of registry patients would have been excluded from clinical trials enrolment. Patients ineligible for RCTs had increased adjusted hazard ratios (95% CI) of: infections and infestations (2.3, 1.7-3.1; P < 0.001), cardiac (8.2, 3.5-25.6; P < 0.001), gastrointestinal (3.5, 1.52-8.0; P < 0.001), hepatobiliary (5.6 1.7-19.1; P < 0.001), psychiatric (4.7, 1.5-14.1; P = 0.006) and eye disorders (4.8 1.5-15.6; P = 0.008), compared to those eligible for RCTs. Incidence rates in the trial eligible patients were similar to those reported from RCT rates. CONCLUSIONS: This study establishes treatment modalities in use for severe psoriasis and the clinical rates of AEs associated with biologic therapy.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

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.

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.

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.

Biologics and dermatology life quality index (DLQI) in the Australasian psoriasis population.

BACKGROUND/OBJECTIVES: Psoriasis is a chronic condition that may require long-term treatment for disease control. This analysis utilizes data from the Australasian Psoriasis Registry with particular attention to the impact of biologic therapy on DLQI, and the differences between the biologics in terms of DLQI score change. METHODS: A retrospective review of patients enrolled in the Australasian Psoriasis Registry from April 2008 to August 2016 was conducted. All subjects from the registry that had DLQI and Psoriasis Assessment Severity Index (PASI) scores recorded at a baseline time point of treatment commencement, in addition to week 12 and 24 post commencement were included in the study. A window of ±3 weeks was permitted at these time points. Multivariate linear regression analysis was undertaken to identify significant predictors associated with change in DLQI. RESULTS: Significant predictors of reduction in DLQI and PASI score from baseline to week 24 include use of adalimumab, infliximab, secukinumab and ustekinumab. Other therapies, including etanercept and oral systemic agents did not show significant change. Each class of biologic showed significant reductions in DLQI score, with IL-12/23 blockade showing the greatest reduction. Significant predictors of lack of reduction in DLQI score include a baseline PASI score <16, and history of diabetes, alcoholism or uveitis. CONCLUSIONS: Patients with moderate to severe chronic plaque psoriasis who are treated with biologics show the greatest reduction in DLQI score, compared with other treatments. Australian dermatologists are prescribing biologics when patients qualify for them in keeping with current guidelines.

Five-year experience with infliximab: Follow up of the product familiarisation program.

This 5-year retrospective analysis is of 22 patients who participated in the product familiarisation program (PFP) at St Vincent's Hospital Melbourne, prior to the listing of infliximab on the Pharmaceutical Benefit Scheme. Criteria for inclusion were being an adult with chronic plaque psoriasis, having a psoriasis area and severity index (PASI) score of at least 15 with an inadequate response or intolerance to three of the following: phototherapy, acitretin, cyclosporin and methotrexate. Participants were infused with infliximab 5 mg/kg on the standard induction (weeks 0, 2 and 6) and maintenance (8-weekly) protocols. At each visit PASI and dermatology life quality index (DLQI) scores were recorded. Success was determined as the proportion of patients achieving at least a 75% improvement in the PASI score from baseline (PASI 75). At 60 months after commencement of therapy, 31% of patients remained on infliximab. Those who did retained PASI 75 with a DLQI of 0 or 1. Of those who ceased infliximab, nine did so due to loss of efficacy, three for personal reasons, two for serious adverse events and one was lost to follow up. Adverse events included non-melanoma skin cancers, infections and abnormal liver enzymes. Infliximab in the Australian context has proven to be a highly effective treatment of chronic plaque psoriasis, and patients who remained on the drug derived a high level of satisfaction, assessed both subjectively (DLQI) and objectively (PASI 75). The variable response indicates that psoriasis is a heterogeneous disease and investigation into potential patient selection for treatment in the future is warranted.

Chronic actinic dermatitis: a retrospective analysis of 44 cases referred to an Australian photobiology clinic.

A retrospective study was performed to analyse the clinical and photobiological features and therapeutic outcomes of 44 patients with chronic actinic dermatitis who were evaluated over an 8.3-year period. The study population comprised 37 men and seven women with a mean age of 62.7 years (range 26-85 years). The most common abnormal phototest results were decreased minimal erythema doses to both UVA and -B (73.8%), and to UVA alone (14.3%). Twenty-six patients (78.8%) had at least one allergic, photoallergic or combined allergic/photoallergic reaction. A total of 139 positive contact or photocontact reactions were recorded (mean 4.2 per patient). Most commonly, treatment consisted of photoprotection, topical corticosteroids and episodic use of systemic agents, in particular azathioprine.

Actinic prurigo: a retrospective analysis of 21 cases referred to an Australian photobiology clinic.

Actinic prurigo (AP) is a rare acquired idiopathic photodermatosis, reported most often in American Indians, but also in Caucasian and Asian populations. The skin lesions in AP predominantly affect exposed sites but may involve covered areas, and often result in postinflammatory scarring. The diagnosis of AP can be difficult and relies on a combination of history, clinical experience and investigations including phototesting and human leucocyte antigen typing. Twenty-one patients (17 women, four men) diagnosed with AP at the photobiology clinic at St Vincent's Hospital Melbourne were reviewed in this retrospective study. The mean age of patients at presentation to the clinic was 25 years, with the mean age of onset being 14 years. Phototesting was undertaken in 20 patients, with 12 (60%) having reduced and eight (40%) normal minimal erythema doses. Human leucocyte antigen typing indicated 18 patients (85.7%) were DR4 positive, with further subtyping of the DR4 allele establishing that 15 patients (71.4%) were DRB1*0407 positive and that two (9.5%) were DRB1*0401 positive. This condition is often recalcitrant, with treatment options including photoprotection, topical and oral corticosteroids, antimalarials, phototherapy and thalidomide.