Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study.

INTRODUCTION: Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders). OBJECTIVE: To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment. MATERIAL AND METHODS: Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators. RESULTS: In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001). CONCLUSION: A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

Family recurrence risk of alopecia areata in the Faroe Islands.

BACKGROUND: Reports of a positive family history of alopecia areata (AA) have led to the assumption of a genetic component. The Faroe Islands population is small, has been isolated until the 20th century, and is served by only one dermatology clinic, making it highly suitable for genealogical studies. AIM: To determine the incidence of AA and to estimate the recurrence risk ratio (RRR) in five generations and in a nationwide dermatologist-based AA cohort using the Faroese genealogy database. METHODS: All registered cases of AA during the period 1973-2011 were identified from the Faroese national dermatology clinics. The AA cases were linked with the genealogy database covering the entire Faroese population, and the probability of AA among first-, second- and third-degree relatives was calculated. RESULTS: In total, 178 cases of AA were identified, giving a crude incidence of 10.1 per 100 000 person-years (10.9 for women and 9.4 for men). The cumulative incidence proportion over life was 0.8%. There was no apparent trend in the probabilities for AA in first-degree family members compared with second- and third-degree relatives. RRR was > 1 in second-degree family members only. CONCLUSION: A lower prevalence rate of AA was found than previously published. The genealogical study failed to identify any apparent trend in the RRR estimates, questioning the role of genetic factors in AA in the Faroe Islands. However, it is possible that the trend is masked by bias and low power; larger studies are therefore warranted to estimate the heritability of AA.

Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis.

BACKGROUND: Real-life data on newer biological and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab and ustekinumab) and compare originators with biosimilars (i.e. Enbrel with Benepali, and Remicade with Remsima). METHODS: The DERMBIO registry contains data on all Danish patients with moderate-to-severe plaque psoriasis treated with biologics. We examined patients treated between 1 January 2007 and 31 March 2017. We used Kaplan-Meier survival curves and Cox regression to examine drug survival patterns. RESULTS: A total of 3495 treatment series (2161 patients) were included (adalimumab n = 1332; etanercept n = 579; infliximab n = 333; ustekinumab n = 1055 and secukinumab n = 196). Secukinumab had the highest number of PASI 100 (100% improvement from baseline Psoriasis Area and Severity Index) respondents, but also the lowest drug survival among all the biologics. Ustekinumab had the highest drug survival overall. There were no significant differences in discontinuation risk between originator and biosimilar versions of infliximab or etanercept. Treatment with higher than approved dosages was frequent for all drugs except for adalimumab and secukinumab. Adverse events (predominantly infections) were most frequent for secukinumab compared with the other agents. CONCLUSIONS: Ustekinumab was associated with the highest drug survival, and secukinumab with the lowest, although most patients on secukinumab were non-naïve. Switching from originator to biosimilar had no significant impact on drug survival, and the safety profiles were comparable. Adverse events occurred most frequently with secukinumab. Future studies are warranted to assess the long-term safety of novel biologics for psoriasis.

Characteristics of patients receiving ustekinumab compared with secukinumab for treatment of moderate-to-severe plaque psoriasis - nationwide results from the DERMBIO registry.

BACKGROUND: While safety and efficacy of ustekinumab and secukinumab, monoclonal antibodies approved for psoriasis, are described in clinical trials, data on their real-life application are lacking. OBJECTIVE: We compared the characteristics of patients initiating first-time treatment with secukinumab or ustekinumab. METHODS: All Danish patients with moderate-to-severe plaque psoriasis treated with biologics are recorded in the nationwide DERMBIO registry. We compared characteristics of patients starting first-time therapy with ustekinumab and secukinumab, respectively. RESULTS: We identified a total of 1037 and 142 first-time treatment series with ustekinumab and secukinumab. There was a male predominance in both groups, but patients initiating secukinumab were slightly older and with longer disease duration; in agreement with guidelines for biologic treatment in Denmark where ustekinumab has been first line for all with psoriasis without joint problems since 2012, and secukinumab first line for psoriasis with joint problems since July 2016. A total of (52.9% and 14.5%) patients receiving ustekinumab and secukinumab, respectively, were bio-naïve. The mean dermatology life quality index score was slightly higher for ustekinumab than secukinumab (11.6 vs. 10.0; P = 0.0769); the mean Psoriasis Area and Severity Index score were significantly higher (10.4 vs. 7.3; P < 0.0001) for ustekinumab. Prevalence of joint disease was markedly lover (22.7% vs. 44.4%) among patients receiving ustekinumab. CONCLUSIONS: We found significant differences in characteristics of patients starting therapy with ustekinumab and secukinumab in a real-life clinical setting. These findings may aid clinicians and researchers when interpreting efficacy data derived from clinical trials and biologic registries of patients with psoriasis.

Myocardial function and effects of biologic therapy in patients with severe psoriasis: a prospective echocardiographic study.

BACKGROUND: Psoriasis is a chronic inflammatory disease and is associated with cardiovascular events. Little is known about subclinical myocardial dysfunction and potential changes in myocardial function during anti-inflammatory treatment in these patients. We prospectively studied left ventricular function in patients with severe psoriasis who initiated biologic therapy. METHODS: Between November 1 2013 and May 31 2014 the study subjects underwent physical, laboratory and comprehensive echocardiographic examination at baseline and after 3 months of treatment. Pearson correlation coefficients and Student's t-test were applied to assess changes in diastolic function (defined as the E/e' ratio) and global longitudinal strain (GLS). RESULTS: Eighteen patients with severe psoriasis treated with biologic therapy with a mean follow-up of 85.6 ± 18.2 days were included. The patients had a baseline psoriasis area and severity index (PASI) of 12.0 ± 4.1 and normal left ventricular ejection fraction [(LVEF) 56.3 ± 3.8%], diastolic dysfunction (E/e' 8.1 ± 2.1) and GLS (-16.8 ± 2.1%). At follow-up, an improvement (baseline vs. follow-up) of PASI (12.0 ± 4.1 vs. 2.7 ± 3.1, P < 0.001), E/e' (8.1 ± 2.1 vs. 6.7 ± 1.9, P ≤ 0.001) and GLS (-16.8 ± 2.1 vs. -18.3 ± 2.3%, P < 0.001) were recorded. No changes were demonstrated in LVEF (56.3 ± 3.8 vs. 56.8 ± 3.3%, P = 0.31), body mass index (30.9 ± 5.7 vs. 31.0 ± 5.8 kg/m(2) , P = 0.90), mean arterial blood pressure (103.1 ± 8.5 vs. 103.7 ± 10.8 mmHg, P = 0.74). Likewise, no changes were seen in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated haemoglobin. CONCLUSION: In patients with severe psoriasis treatment with biologic therapy was associated with improved PASI and amelioration of myocardial dysfunction.

Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris.

BACKGROUND: Drug survival (time to drug discontinuation) has recently emerged as an important parameter reflecting the long-term therapeutic performance in a real-life setting. Biologic drug survival in psoriasis is mainly limited by a gradual loss of efficacy over time. Previous studies have been limited by small patient population size and short observation times and yielded discrepant survival times for different biologics. OBJECTIVES: To calculate the long-term drug survival for adalimumab, etanercept, infliximab and ustekinumab in a large cohort of real-life patients with psoriasis vulgaris and to analyse the factors that influence drug survival. PATIENTS AND METHODS: Data were extracted from the prospective registry DERMBIO covering all patients with psoriasis vulgaris treated with biologic agents in the academic centres in Denmark. Drug survival was analysed using the Kaplan-Meier method. The influence of different covariates on drug survival was analysed by Cox regression. RESULTS: Included in the analysis were 1867 treatment series (adalimumab n = 774, etanercept n = 449, infliximab n = 253, ustekinumab n = 391) administered in 1277 patients for up to 10 years. Drug survival was significantly longer for ustekinumab than for anti-tumour necrosis factor (TNF)-α agents (P < 0·001). Etanercept had the shortest survival time [median survival 30 months, 95% confidence interval (CI) 25·1-34·9] whereas adalimumab and infliximab had comparable survival rates (59 months, 95% CI 45·6-72·4; 44 months, 95% CI 33-54·9, respectively). Survival was longer in men [odds ratio (OR) 1·51, 95% CI 1·31-1·74 vs. women] and in patients who had not previously received any biologic agent (OR 1·24, 95% CI 1·05-1·46). Loss of efficacy accounted for 67% of all drug discontinuations. CONCLUSIONS: Ustekinumab has a significantly longer drug survival than the anti-TNF-α agents. Switching from one biologic to another is associated with an impairment of drug survival. Preventing loss of efficacy is a major area of medical need in the biologic therapy of psoriasis and the strategies that improve drug survival should be further investigated.

Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort.

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow-up of 5 years were included. Incidence rates per 1000 patients-years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0.34-0.83) was associated with reduced risk of the composite endpoint and a comparable but non-significant protective effect was observed with biological drugs (HR 0.58; CI 0.30-1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26-4.27) and retinoids (HR 1.80; CI 1.03-2.96). Tumour necrosis factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not. CONCLUSION: Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events during long-term follow-up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies are called for.

Do generalists and specialists agree on descriptive acne morphology?

BACKGROUND: Acne is a common skin disease, which is treated by many different specialities. Clinical guidelines for treatment are based on the recognition of acne morphology. The assessment of acne morphology is therefore an important element of the proper diagnosis and treatment of acne. OBJECTIVE: To evaluate the level of congruence in the assessment of acne morphology in General Practitioners (GPs) and Dermatologists compared to the assessment of an expert. METHODS: The study was conducted during 2008-2009. Randomly selected GP and Dermatologists Practitioners, (DPs) from Denmark were invited to complete an on-line questionnaire. The questionnaire was based on seven cases, each presented with digital photos and a short history. The respondents were asked to identify the morphology by marking their answer on a closed list. Congruence, variation and the participants' assessment were compared with a priori expert assessment using odds ratios, Fishers exact test and Index of Qualitative Variation. RESULTS: Of the 1700 GPs and 110 DPs invited, 355 GPs and 99 DPs participated. In all seven cases, DPs were more in accordance with expert opinion than were GPs. In addition, the GPs had a greater variation in the distribution of answers. CONCLUSION: GPs described acne morphology recognized clinical hallmarks of severity in acne less well than dermatologists and were far less consistent.

Teledermatology with an integrated nurse-led clinic on the Faroe Islands--7 years' experience.

BACKGROUND: Telemedicine is an increasingly suggested answer to the problem of providing high-class medical service to rural and remote areas in a modern society. Dermatology is a promising candidate for telemedical service, because it is well suited for clinical questions forwarded together with photographs. OBJECTIVES: To describe the patient population of the Faroe Islands dermatology clinic with respect to distribution of diagnoses, treatment, duration, response time and patient flow. METHODS: Case notes were drawn from all dermatology consultations managed during 2003-2009 through the national teledermatology system. These were compared with case notes drawn from the same journal system from the regular outpatient clinic. RESULTS: Over the last 7 years, a total of 9161 consultations in 7.7% of the population have been performed. The demography of the patient population reflects the underlying population apart for an over-representation of the female gender in younger years. The disease spectrum is comparable with what has been reported in other outpatient clinics, except for the relative absence of skin cancer and pigmented lesions, for which regular outpatient consultation is reserved. LIMITATIONS: The study is descriptive. CONCLUSIONS: The experience derived suggests that teledermatology may serve as a near-adequate alternative to a regular private practice, if abstaining from treating minor common skin conditions and purely cosmetic conditions is acceptable.

Photodynamic therapy in a series of rosacea patients.

BACKGROUND: Rosacea is a common disease that often has a chronic intermittent course despite current treatment; therefore, additional treatment options are desirable. The pathogenesis of the disease is unknown. OBJECTIVES: We have previously suggested that photodynamic therapy (MAL-PDT) may be of benefit as rosacea therapy. The purpose of this study was to further assess the possible benefit of this treatment of rosacea. METHODS: An exploratory review of case notes from rosacea patients treated with PDT was performed. Patients referred to our department with rosacea were offered PDT if requesting an alternative to previously tried conventional therapy. Routine MAL-PDT with methylaminolevulate and red light was given one to four times; results were evaluated 1-2 months after PTD was initiated and subsequently followed up. RESULTS: Good results were seen in 10 out of 17 patients, and fair results in another 4 patients. The majority of patients treated could stop or significantly reduce other rosacea therapy for a period lasting from about 3 months and up to 2 years. The study is limited by strong selection bias, and the clinical evaluation was obtained from case notes and photos. CONCLUSIONS: An apparent effect of MAL-PDT on rosacea could be observed. This is in accordance with our previous experience, and observations made by other researchers. A future randomized controlled trial therefore seems justifiable.

Airborne contact dermatitis from Coleus plant.

A 65-year-old woman with a 25-year history of facial dermatitis and no obvious external cause was patch tested with her houseplants and a wide range of common allergens. The only positive reaction found was to the plant Coleus blumei.

Allergic contact dermatitis from 3-iodo-2-propynyl-butylcarbamate (IPBC) - an update.

Results from 3 1/2 years of routine patch testing with 3-iodo-2-propynyl-butylcarbamate (IPBC) are presented. From 1996 to 1999, a total of 3168 persons (2093 women and 1075 men) were patch tested with IPBC, and 7 cases were found to be positive. In 2 cases, sensitization could be attributed to cosmetics, and in a further 2 cases cosmetics were the most likely cause of sensitisation. It is concluded that the use of IPBC in cosmetic products can lead to contact sensitization and allergic contact dermatitis. 2 of the 7 reported cases with IPBC allergy were also found positive to thiuram, and possible cross-reactivity between IPBC and thiuram is discussed.

Risk factors influencing the development of hand eczema in a population-based twin sample.

BACKGROUND: A population-based twin study has recently shown that genetic factors are of significance for hand eczema. OBJECTIVES: To characterize further a sample of this twin material with regard to contact allergy, atopic dermatitis and wet work. METHODS: In total, 1076 individual twins were examined clinically and patch tested. The diagnosis of atopic dermatitis was based on the U.K. Working Party criteria. The decision concerning wet work was based on the individual job description, taking into account the later introduced definition of at least 2 h of water exposure daily. The data were analysed by a newly developed statistical method which makes it possible to analyse the individual risk factor and at the same time discriminate between genetic and environmental factors. RESULTS: The statistical analysis confirmed atopic dermatitis as an important risk factor for hand eczema. Contact allergy was also confirmed as a significant risk factor for hand eczema, and the risk was related to strength (+ to + + +) of contact allergy. The results indicated that the high frequency of hand eczema in women in comparison with men was caused by environmental and not genetic factors. Aggregation of hand eczema within twin pairs was only to a minor degree explained by atopic dermatitis and nickel allergy (or other contact allergies). CONCLUSIONS: We suggest that a hitherto unrecognized genetic risk factor for hand eczema independent of atopic dermatitis and contact allergy is probably of importance for the development of irritant contact dermatitis on the hands.

Iodopropynyl butylcarbamate: a new contact allergen.

Iodopropynyl butylcarbamate (IPBC) has been used for years as a fungicide and bactericide for wood and paint preservation without any reports of cutaneous side-effects. During the last few years, it has entered cosmetic products and is temporarily permitted in the EU Cosmetics Directive in a use concentration of 0.1%. In the present study, we report our preliminary experience with patch testing consecutive contact dermatitis patients with IPBC. A patch test concentration of 0.1% seems appropriate for initial screening but deserves further evaluation. Among 311 consecutive patch test patients, 3 patients with a positive patch test to IPBC have been identified. Contact allergy is likely in at least 1 case, based on clinical history, exposure history, patch testing with dilution series, ROAT and chemical analysis.

Hand eczema in twins: a questionnaire investigation.

Hand eczema in a population-based twin cohort of 6666 persons aged 20-44 years was investigated by means of a questionnaire regarding skin symptoms on the hands and self- or physician-diagnosed hand eczema. Genetic influence was observed by significant differences between identical and fraternal twins regarding casewise concordance rate and correlations in liability under the threshold model. The casewise concordance rates were almost twice as high in identical compared with fraternal twins in both sexes. By extension of the threshold model a joint analysis could be performed, resulting in a heritability estimate of 0.65. Tendencies towards stronger genetic influence for men and for younger individuals were present, but neither was statistically significant. No particular symptom pattern expressed especially strong or weak genetic influence. Hereditary factors for hand eczema were observed despite a presumably substantial individual-specific environmental variation. The hypothesis that hereditary risk factors may play a significant part in the development of hand eczema in the general population, when no extreme environmental exposure exists, seems justifiable. The relevance of known individual risk factors such as atopic dermatitis or contact allergy in relation to heredity remains to be analysed. The possible importance of age and temporal change also needs further consideration.