Gabapentin and oral antidepressants for chronic pruritus: a prospective cohort study evaluating efficacy and side effects in daily dermatological practice.

BACKGROUND: Chronic pruritus is frequently seen in daily dermatological practice and is associated with marked impact on quality of life. Research on the use of gabapentin and oral antidepressants in daily dermatological practice is scarce. OBJECTIVE: To evaluate the efficacy and safety of gabapentin and oral antidepressants in patients with chronic pruritus in daily clinical practice. METHODS: A prospective observational single-center cohort study was conducted including adult patients with chronic pruritus and an indication for systemic treatment between June 2016 and May 2019. RESULTS: Systemic treatment with gabapentin and/or antidepressants was initiated in 31 patients with severe chronic pruritus (median average pruritus NRS score 7.0), in which most cases no underlying origin was identified (83.9%). In patients treated with gabapentin 900-1800 mg/day (N = 25), median average pruritus NRS decreased to 5.5 (IQR 3.0) after 4 weeks and remained stable up to 24 weeks of treatment. Efficacy of antidepressants was variable, with the highest response after initiation of amitriptyline, nortriptyline, and mirtazapine. Side effects were frequently observed in both gabapentin and antidepressant treatments; however, were mostly mild and temporary. LIMITATIONS: This was a single-site observational study, with limited sample size. CONCLUSION: Treatment with gabapentin and antidepressants should be considered in patients with chronic pruritus unresponsive to conventional treatment.

Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

Two-year follow-up of a dose reduction strategy trial of biologics adalimumab, etanercept, and ustekinumab in psoriasis patients in daily practice.

BACKGROUND/OBJECTIVES: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission. METHODS: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed. RESULTS: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC. CONCLUSIONS: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

Structure, quality and accessibility of the Dutch acne healthcare; a care providers' perspective.

Background: Despite the wide range of available treatment modalities a delay between the first outbreak of acne vulgaris and an effective treatment outcome is experienced by many patients. Considering the growing incentives to improve patient satisfaction and quality of care while reducing healthcare costs, insights into the structure, quality and accessibility of acne healthcare services beyond guidelines are therefore needed.Objective: To provide insights into the structure, quality and accessibility of acne healthcare services.Methods: A qualitative study was conducted according to the principles of 'situational analysis'. The Dutch acne healthcare system was taken as an illustrative example. Twenty-four semi-structured interviews were conducted among representatives of the 4 main Dutch professions providing acne care. All interviews were audiotaped, transcribed verbatim and analyzed.Results: Multiple facilitators and barriers emerged from the interviews. Identified facilitators were care providers delivering personalized patient care and having a positive attitude toward formalized multidisciplinary care delivery. A lack of streamlined referral pathways and standardization in acne severity-assessment, financial aspects and unfamiliarity with the content and added value of other acne care professionals were identified as barriers. Further research is recommended to investigate how de-medicalisation, the gatekeepers role, and the impact of location and work setting influence the quality of and accessibility to care.Conclusions: Identified facilitators and barriers and an overall positive attitude of care providers toward multidisciplinary care provision provides opportunities for the utilization of future guidelines involving streamlined referral pathways and good working arrangements between all acne care providing professions.

Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis. METHODS: Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY). RESULTS: Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time. CONCLUSIONS: No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.

Frailty screening in dermato-oncology practice: a modified Delphi study and a systematic review of the literature.

BACKGROUND: Appropriate management and prevention of both under- and overtreatment in older skin cancer patients can be challenging. It could be helpful to incorporate frailty screening in dermato-oncology care, since frailty is associated with adverse health outcomes. OBJECTIVES: This study aimed to identify and prioritize the requirements a frailty screening tool (FST) should fulfil in dermato-oncology practice and to select the best existing FST(s) for this purpose. METHODS: A modified two-round Delphi procedure was performed among 50 Italian and Dutch specialists and patients to review and prioritize a list of potential FST requirements, using a 5-point Likert scale. Consensus was defined as a mean score of ≥4.0. A systematic literature search was performed to identify existing multidomain FSTs, which were then assessed on the requirements resulting from the modified Delphi procedure. RESULTS: Consensus was achieved on evaluation of comorbidities (4.3 ± 0.7), polypharmacy (4.0 ± 0.9) and cognition (4.1 ± 0.8). The FST should have appropriate measurement properties (4.0 ± 1.0), be quickly executed (4.2 ± 0.7), clinically relevant (4.3 ± 0.7), and both easily understandable (4.1 ± 1.2) and interpretable (4.3 ± 0.7). Of the 26 identified FSTs, four evaluated the content-related domains: the Geriatric-8 (G8), the modified Geriatric-8 (mG8), the Groningen Frailty Indicator (GFI) and the Senior Adult Oncology Program 2 (SAOP2) screening tool. Of these, the G8 was the most extensively studied FST, with the best psychometric properties and execution within 5 min. CONCLUSIONS: The G8 appears the most suitable FST for assessing frailty in older adults with skin cancer, although clinical studies assessing its use in a dermato-oncology population are needed to further assess whether or not frailty in this particular patient group is associated with relevant outcomes (e.g. complications and mortality), as seen in previous studies in other medical fields.

Psoriasis severity: commonly used clinical thresholds may not adequately convey patient impact.

BACKGROUND: Psoriasis severity is usually evaluated using quantitative and qualitative measures, including per cent body surface area (BSA) involvement, the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), a patient-reported questionnaire. However, standardized definitions for psoriasis severity categories have not been well established. A PASI of 10 or 12 has remained the minimal severity threshold defining eligibility for psoriasis treatments. In the present study, the validity of this cut-off was re-evaluated in the context of quality of life. OBJECTIVE: To determine whether the thresholds commonly used to define moderate psoriasis (PASI of 10-12 and BSA of 10) are supported by patient-reported DLQI data. METHODS: A systematic review of randomized controlled trials that enrolled mild or moderate patients published between January 2000 and June 2017 was used to assess correlations between provider and patient-generated severity at baseline. RESULTS: For subject groups with high impact on quality of life (DLQI > 10), the mean weighted BSA was 7.6 (Range: 7.1-8.4) and the mean weighted DLQI was 11 (Range: 10.2-12.2). Similarly, the mean weighted PASI for patients with DLQI > 10 was 8.7 (Range: 7.1-10.1) and the mean weighted DLQI was 10.9 (Range: 10.1-12.2). CONCLUSION: Patients with PASI or BSA scores less than 10 can have major quality of life impairment. In general, the objective measures of BSA and PASI alone, when excluding DLQI, may not fully capture the impact of disease severity.

Topical treatment of psoriasis: questionnaire results on topical therapy as long-term continuous treatment and use on specific body sites.

BACKGROUND: Currently, no formalized international consensus guidelines exist to direct optimal topical treatment including long-term treatment. OBJECTIVE: In this survey, we aim to examine if and which topicals are used in clinical practice in long-term continuous treatment of psoriasis and how topicals are used in treating specific sites of the body. METHODS: A questionnaire was distributed electronically to dermatologists from the International Psoriasis Council (IPC) representing 26 countries. RESULTS: The top three topicals used across all severities of disease were topical corticosteroids, vitamin D analogs, and potent topical corticosteroids in combination with vitamin D analogs. On locations where the skin is thin, flexural and genital psoriasis, lower potency topical corticosteroids were used, whereas on other sites, in particular in palmoplantar psoriasis, superpotent topical corticosteroids and combination vitamin D analogs/corticosteroids were used. CONCLUSIONS: It is relevant to optimize localized therapy for all severities of psoriasis reconciling disease activity (stable vs. unstable disease), localization of the lesions and the individual patient and his/her perspectives on disease control. Topical therapies are valuable treatments for classical mild disease and may have a position in some patients with more severe manifestations.

Phototherapy in the perspective of the chronicity of psoriasis.

According to the guidelines for the treatment of psoriasis, phototherapy is given in courses of UVB exposure starting at 50-70% of the minimal erythema dose, MED, with subsequently incremental dosages, but keeping erythemal skin reactions to a minimum by restraining the dosages when necessary. In this review, this classical principle of short-term near erythematogenic UVB therapy without further UVB maintenance therapy is challenged as it is evidently not optimal for psoriasis as a chronic condition. There is old experimental evidence supplemented with growing knowledge on the mode of action of phototherapy and more recent data on low-level UVB regimens as maintenance therapy that should urge us to revisit our guidelines on phototherapy to address psoriasis for what it is: a chronic condition.

Quality of life outcomes in adults with moderate-to-severe plaque psoriasis treated with dimethylfumarate (DMF): a post hoc analysis of the BRIDGE study.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with quality of life (QoL) impairment. BRIDGE was a randomized, double-blind, phase III study comparing the efficacy and safety of dimethylfumarate (DMF) with a fixed combination of fumaric acid esters (FAE) or placebo for the treatment of moderate-to-severe psoriasis. OBJECTIVES: This post hoc analysis investigated treatment effect on QoL overall and by patient subgroups categorized by disease severity. Week 8 efficacy responses were also investigated as possible predictors of Week 16 Dermatology Life Quality Index (DLQI) outcomes. METHODS: Patients were randomized to receive a maximum daily dose of 720 mg of DMF, FAE (gradual up-titration) or placebo for 16 weeks. Psoriasis Area Severity Index, Body Surface Area, Physician's Global Assessment and DLQI were assessed at baseline, Weeks 8 and 16. DLQI 0-1 indicated 'no effect on patient life'. Associations between baseline severity, Week 16 DLQI and Week 8 efficacy (as observed cases) were also examined. RESULTS: At baseline, 671 patients were included in the full analysis set (267 randomized to DMF, 273 to FAE and 131 to placebo). DMF was superior to placebo (P < 0.001) and not significantly different to FAE regarding Week 16 DLQI outcomes (P > 0.05). Baseline disease severity did not impact DLQI outcomes at Week 16. In DMF- and FAE-treated patients, Week 8 PASI 50/75 responders reported better DLQI responses at Week 16 vs non-responders (P < 0.05). Week 8 PASI ≤ 3 and/or PGA 0-1 responders were also more likely to report DLQI 0-1 at Week 16 vs non-responders (P < 0.05). CONCLUSION: Dimethylfumarate significantly improved DLQI outcomes vs. placebo and was not affected by baseline disease severity. Efficacy responses (PASI 50/75, PASI ≤3 and PGA 0-1) as early as Week 8 were predictive of QoL outcomes at Week 16 in DMF- and FAE-treated patients.

Severity, heterogeneity and systemic inflammation in psoriasis.

Psoriasis may express as active severe disease or as mild stable disease. In particular, patients with active severe disease present systemic involvement, including comorbidities and increased values of parameters reflecting an active state of innate immunity. In contrast, patients with mild stable disease show a dominancy of acquired immunity. In this review article, we report the clinical aspects of disease manifestations of both active and quiescent psoriasis as well as the immunological aspects, as well as the impact on antimicrobial resistance. The activity of psoriasis is not captured in the present outcome measures for severity assessment. The present review suggests that incorporating disease activity may be important in the assessment of the efficacy of treatments.