Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. Methods: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 µg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. Findings: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Interpretation: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Funding: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

Simple, low-cost group-counselling programme vs treatment as usual for patients with newly notified occupational hand eczema-Exploratory analyses of effects on knowledge, behaviour and personal resources of the randomized PREVEX clinical trial.

BACKGROUND: Sickness absence in hand eczema patients has been associated with stress rather than disease severity, indicating that personal aspects regarding hand eczema should be investigated further. OBJECTIVES: To examine whether patient education vs treatment as usual can influence behaviour and knowledge regarding skin protection and care, as well as personal resources, in patients with occupational hand eczema. METHODS: PREVEX is an individually randomized clinical trial investigating the 1-year effects of a simple, low-cost group-counselling programme vs treatment as usual for patients with notified occupational hand eczema. Exploratory outcomes were behaviour, knowledge, self-efficacy, and self-evaluated skin care ability. RESULTS: In total, 1668 patients with notified occupational skin disease were invited to participate, of whom 769 were randomized and 756 were analysed: intervention group (n = 376) vs control group (n = 380). Behaviour was improved and the knowledge score increased in the intervention group as compared with the control group (respectively: estimate 0.08; 95%CI: 0.02-0.19; P = .01; and estimate 0.49; 95%CI: 0.28-0.70; P < .001). Self-efficacy was lower in the intervention group as compared with the control group (estimate -0.78; 95%CI: -1.25 to -0.30; P = .001). No difference was found regarding skin care abilities. CONCLUSIONS: The intervention had a positive influence on 1-year behaviour and knowledge, but was insufficient to result in long-term positive changes in personal resources regarding dealing with hand eczema.

Impact of hand eczema on quality of life: metropolitan versus non-metropolitan areas.

BACKGROUND: An inverse relationship between disease severity and health-related quality of life (HR-QoL) in patients with hand eczema is well established, but modifying effects of demographic variables have been less well studied. OBJECTIVE: To identify the influence of metropolitan versus non-metropolitan residence on the relationship between disease severity and HR-QoL in patients with occupational hand eczema. METHODS: The city of Copenhagen and the rest of Zealand were defined as metropolitan and non-metropolitan areas, respectively. Participants were 773 persons with occupational hand eczema. A questionnaire on the severity of hand eczema and HR-QoL was sent to all participants. RESULTS: The odds for reporting moderate to high severity of occupational hand eczema were significantly lower in the metropolitan population than in the non-metropolitan population [odds ratio (OR): 0.42; 95%CI: 0.23-0.75], whereas low dermatology-related quality of life was more prevalent in metropolitan than in non-metropolitan patients (OR: 1.31; 95%CI: 0.83-2.05), indicating that hand eczema had a more pronounced negative effect in metropolitan patients, in spite of less severe eczema. CONCLUSION: Our data indicate that area of residence has a modifying effect on the relationship between disease severity and HR-QoL, with a more negative impact on HR-QoL in metropolitan than in non-metropolitan areas. This information is important with respect to fully appreciating the burden of occupational hand eczema.

Associations between lifestyle factors and hand eczema severity: are tobacco smoking, obesity and stress significantly linked to eczema severity?

BACKGROUND: It has been suggested that lifestyle factors such as smoking, overweight and stress may influence the prevalence and severity of hand eczema. OBJECTIVES: To investigate the association between lifestyle factors and hand eczema severity in a cohort of patients with work-related hand eczema. METHODS: Individuals with work-related hand eczema notified in the period between June 2012 and November 2013 were included in this questionnaire-based cross-sectional study. Participants responded to a questionnaire including questions on lifestyle factors, as well as a photographic guide for assessment of severity of hand eczema and questions on quality of life. RESULTS: A total of 773 individuals (546 women and 227 men) responded to the questionnaire and were included in the study. A strong association was found between tobacco smoking and hand eczema severity (p = 0.003), whereas no significant association was found for body weight and stress. Other factors linked to severe eczema were male sex and older age (p = 0.04 and p = 0.01, respectively), and wet work (p = 0.08). CONCLUSION: The data from the present study strongly support an association between smoking and hand eczema severity. However, owing to the cross-sectional design of the study, no conclusion on causation can be drawn.

Tobacco smoking and hand eczema - is there an association?

BACKGROUND: Numerous risk factors have been suggested for hand eczema. This systematic review evaluates the association between tobacco smoking and hand eczema. OBJECTIVE: To review the literature systematically on the association between smoking and hand eczema. METHODS: The PubMed and EMBASE databases were searched up to 27 January 2015 for articles on the association between tobacco smoking and hand eczema, including human studies in English and German only. Experimental studies, studies on tobacco allergy, case reports, reviews and studies on second-hand smoking were excluded. RESULTS: Twenty articles were included. Among studies in occupational settings, three of seven found a statistically significant positive association between tobacco smoking and hand eczema prevalence rate, as did four of eight population-based studies. The association was stronger for studies in occupational settings than for population-based studies. No studies reported tobacco to be a clear protective factor for hand eczema. Two of five studies regarding severity found a positive association between smoking and hand eczema severity. CONCLUSION: Overall, the data indicate that smoking may cause an increased frequency of hand eczema, particularly in high-risk occupations. However, data from studies controlling for other risk factors are conflicting, and few prospective studies are available. Studies controlling for other risk factors are needed, and information regarding the diagnosis of subclasses of hand eczema, as well as severity, may be important.