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Summary: Background: Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side‐effects limit its use. Dupilumab, a fully human anti‐interleukin 4 receptor‐alpha monoclonal antibody, inhibits signaling of IL‐4 and IL‐13, key drivers of Type 2/Th2‐mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately‐controlled moderate‐to‐severe atopic dermatitis in adults. Objectives: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. Methods: In this 16‐week, double‐blind, randomized, placebo‐controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium‐potency TCS from Week −2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. Results: In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P < 0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS. Conclusions: Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Summary: Background: Biological therapies are highly effective in psoriasis, but have profound effects on innate and adaptive immune pathways that may negatively impact on cancer immunosurveillance mechanisms. Objectives: To investigate the risk of cancer in patients with psoriasis treated with biological therapy. Methods: We searched MEDLINE, Embase, and the Cochrane Library (up to August 2016) for randomized controlled trials, prospective cohort studies and systematic reviews that reported cancer incidence in people exposed to biological therapy for psoriasis compared with a control population. Results: Eight prospective cohort studies met our inclusion criteria. All the evidence reviewed related to tumour necrosis factor inhibitors (TNFi) with the exception of one study on ustekinumab. An increased risk of nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma, was reported with TNFi compared with both a general United States population and a rheumatoid arthritis population treated with TNFi. No evidence for increased risk of cancers (reported as all cancers, lymphoma, melanoma, prostate, colorectal and breast cancer) other than NMSC was identified. Conclusions: There were important limitations to the studies identified including choice of comparator arms, inadequate adjustment for confounding factors and failure to account for latency periods of cancer. There remains a need for ongoing pharmacovigilance in relation to cancer risk and biological therapy; the NMSC signal requires further investigation to determine the risk specifically attributable to biological therapy using prospectively collected data with adjustment for known NMSC risk factors. [ABSTRACT FROM AUTHOR]

Summary: Background: Biological therapies are effective treatments for psoriasis and are often prescribed to women of child‐bearing age. Objectives: To evaluate the safety of biological therapy in conception and/or pregnancy. Methods: We performed a systematic review of PubMed, MEDLINE, Embase and Cochrane databases for multivariate‐adjusted studies of women exposed to biologics relevant to the treatment of psoriasis during conception and/or pregnancy. Results: We identified four population‐based cohort studies involving 1300 women exposed to tumour necrosis factor (TNF)‐α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy. These studies showed a trend towards drug‐specific harm with TNFi exposure in women with different inflammatory diseases, with an increased risk of congenital malformations [three studies; odds ratio (OR) range 1·32–1·64] and preterm birth (one study; OR 1·69, 95% confidence interval 1·10–2·60). This trend did not reach statistical significance in all studies; study heterogeneity, variation across comparator cohorts, inadequate adjustment for important confounding variables such as co‐therapy, and an absence of a common constellation of malformations means there is uncertainty about the causal role of TNFi. No studies specifically addressed the effect of TNFi exposure in psoriasis during conception and/or pregnancy, or of interleukin (IL)‐17 and IL‐12/23 antagonists in any indication. Conclusions: When counselling women these findings must be balanced against the potential impact of untreated severe psoriasis on conception and/or pregnancy and maternal wellbeing; ongoing pharmacovigilance via registries remains essential to address this evidence gap. [ABSTRACT FROM AUTHOR]

The article presents a research study on tumour necrosis factor antagonist-induced lupus. Topics discussed include chronic plaque psoriasis and psoriatic arthritis (PsA), human epithelial type-2 speckled nuclear pattern, and licensed treatments for several medical conditions like severe inflammatory conditions, notably psoriasis, rheumatoid arthritis (RA) and inflammatory bowel disease.

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Copyright of British Journal of Dermatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of British Journal of Dermatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients' preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice., Objectives: To quantify patient preferences for an algorithm-based approach to prescribing biologics ('biologic calculator') in psoriasis., Methods: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models., Results: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples., Conclusions: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)