Real-world effectiveness of anti-interleukin-23 antibodies in chronic plaque-type psoriasis of patients from the Austrian Psoriasis Registry (PsoRA).

With the introduction of the latest class of biologic drugs targeting interleukin (IL)-23p19, three new, highly effective drugs can be used for the treatment of chronic plaque psoriasis. However, poorer skin improvement as well as higher rates of serious adverse events have been reported for patients under real-world conditions (outside clinical trials). This accounts especially for patients who have already been treated with biologic drugs. We therefore aimed to determine effectiveness and safety of IL-23p19 inhibitors in real-world patients by analysing data from the Psoriasis Registry Austria (PsoRA) in this observational, retrospective, multicentre cohort study. Data for 197 patients (52.3% biologic-non-naïve), who were treated with anti-IL-23p19 antibodies (127 guselkumab, 55 risankizumab and 15 tildrakizumab) for at least 3 months, were eligible for analysis. In general, biologic-non-naïve patients displayed a less favourable response to anti-IL-23 treatment as compared to biologic-naïve patients. However, after correction for previous biologic exposure, few differences in PASI improvement were detected among biologic-naïve and -non-naïve patients treated with different IL-23p19 inhibitors. This indicates that treatment effectiveness is not related to the class of the previously administered therapy in biologic-non-naïve patients. Therefore, IL-23p19 inhibitors represent a promising treatment alternative for patients who have not responded to previous biologics. However, as with other biologic agents (including IL-17 inhibitors), we did not observe an entirely satisfactory treatment response (i.e. PASI < 3 and/or PASI 75) to anti-IL-23 treatment in one out of four to five patients. Adverse events (mainly non-severe infections) were observed in 23 (11.7%) patients with no major differences regarding the administered IL-23 inhibitor or previous biologic exposure.

Asthma control is not associated with physical activity level in children with asthma during regular follow-up.

OBJECTIVE: Engagement in physical activity (PA) is one of the important aims of long-term asthma treatment. The objective of this study is to evaluate whether improvement of asthma control is associated with enhanced PA during regular follow-up in children with asthma. METHODS: Children, 6-18 years, with asthma were eligible for inclusion when their asthma was uncontrolled at a regular follow-up visit. Participants completed a seven-day recall questionnaire to assess engagement in different physical activities (Physical Activity Questionnaires for Children) at baseline and at the time asthma control was achieved according to predefined criteria. They were also instructed to wear an accelerometer (ActigraphTM GT1M) for seven consecutive days at these timepoints. RESULTS: Thirty children (21 boys), aged 10.5 (2.9) years, with uncontrolled asthma were included. After a median (IQR) follow up time of 163 (94-253) days PA was assessed again. Accelerometer obtained moderate vigorous PA (median (IQR) 56 (43-66) versus 53 (35-63) minutes) as well as self-reported PA (median (IQR) PAQ score 7.4 (5.9-10.1) versus 7.2 (6.5-11.0)) were not significantly different at the time of uncontrolled and controlled asthma. Moderate vigorous PA increased in 46.2%, was comparable in 23.1%, and decreased in 30.7% of patients, respectively. Self-reported PA increased in 19.0%, was comparable in 52.4%, and decreased in 28.6% of patients, respectively. CONCLUSIONS: Based on the results of this study we conclude that asthma control is not associated with self-reported and accelerometer obtained level of physical activity during regular follow-up in children with asthma.

Pruritus Intensity Scales across Europe: a prospective validation study.

BACKGROUND: Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient-reported outcome tools in order to allow determination of the treatment course. OBJECTIVES: So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses. METHODS: After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T-cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter-correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statistically significant correlations were found. CONCLUSIONS: The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries.

Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis.

BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

Cross-European validation of the ItchyQoL in pruritic dermatoses.

BACKGROUND: Chronic pruritus (CP) is a frequently occurring symptom in inflammatory dermatoses, causing a high burden and limitations to health-related quality of life (HRQoL). OBJECTIVE: The ItchyQoL was developed to assess the impairment to HRQoL in patients with CP. However, it has only been validated in English and German. Here, we report the validation in several languages across Europe. METHODS: After professional translation, the versions of ItchyQoL were digitized for use as a tablet application. Validation was performed in clinics for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: Five hundred and thirty-five patients with either contact dermatitis, chronic prurigo - nodular type, psoriasis vulgaris, lichen planus or mycosis fungoides/Sézary syndrome and with CP ≥ 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's-α, all: 0.95) and test-retest reliability (intraclass correlation: 0.91). It strongly correlated with the Dermatology Life Quality Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales in the study population (visual analogue scale r = 0.46; numerical rating scale r = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). CONCLUSION: ItchyQoL is now also validated in French, Italian, Polish, Russian, Spanish and Turkish and can be used in clinical trials in countries speaking these languages.

[Tinea in the genital area : A diagnostic and therapeutic challenge]. / Tinea im Genitalbereich : Eine diagnostische und therapeutische Herausforderung.

Pubogenital tinea or tinea genitalis represents a rare type of dermatophytosis which, however, is increasingly being diagnosed. The mons pubis is affected, but also the outer regions to the penis shaft and the labia together with the groins. Pubogenital tinea is a more superficial erythrosquamous type, but strong inflammatory dermatomycoses of the genital area as tinea genitalis profunda ranging to kerion celsi are observed. A total of 30 patients (14-63 years of age, 11 men and 19 women) with pubogenital tinea are described. Most patients originated from Graz, Austria, while 2 patients were from Germany (Saxony and Isle of Sylt). Causative agents were mainly zoophilic dermatophytes: Microsporum (M.) canis (11), Trichophyton (T.) interdigitale (9), T. anamorph of Arthroderma benhamiae (2), and T. verrucosum (1). Anthropophilic fungi were T. rubrum (6) and T. tonsurans (1). Anamnestic questions should include contact with pets, physical activities, and travel. Genital shaving and concurrent tinea pedis and onychomycosis are disposing factors. Treatment consisted of oral antifungals except in the three women who were pregnant. Preferably, itraconazole or terbinafine was used, while in a single case, fluconazole was administered. Griseofulvin was not used, because this classic systemic antifungal agent is not allowed any more in Austria. In one patient, oral antifungal therapy was changed from itraconazole to terbinafine due to inefficacy.

Methotrexate vs. fumaric acid esters in moderate-to-severe chronic plaque psoriasis: data registry report on the efficacy under daily life conditions.

OBJECTIVE: To compare the clinical efficacy of methotrexate (MTX) vs. fumaric acid esters (FAE) in psoriasis treated under daily life conditions. METHODS: Data were extracted from a registry (http://www.psoriasisregistry.at) of 272 adult patients with moderate-to-severe chronic plaque psoriasis treated primarily with MTX (n = 72) or FAE (n = 200) between 2004 and 2011. Data from all patients, including those who did not complete at least 3 months of monotherapy, were included in an intention-to-treat (ITT) worst-case analysis. RESULTS: Thirty of 72 (41.7%) patients treated with MTX and 85 of 200 (42.5%) patients treated with FAE discontinued early, mainly due to side-effects or lack of response. Among patients who completed at least 3 months of treatment, the response to primary treatment with MTX vs. FAE did not differ significantly at any time point. In the ITT worst-case analysis at month 3, complete remission rate, PASI90, PASI75 and PASI50 rates were 6%, 7%, 24% and 39% in MTX-treated patients vs. 1%, 5%, 27% and 44% in FAE-treated patients. Overall mean PASI reduction score improved significantly in response to primary MTX and FAE treatment (by 10.6% and 12.6%, respectively) between 3 and 6 months (P = 0.0005; exact Wilcoxon test), but not between 6 and 12 months (P = 0.16). A subset of 32 patients who did not respond satisfactorily to primary treatment with FAE responded better to subsequent MTX therapy (P < 0.0001; paired Wilcoxon test). CONCLUSIONS: As shown by retrospective analysis, the primary efficacy of FAE was similar to that of MTX under daily life conditions.

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial.

BACKGROUND: Treatment with the interleukin-12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque-type psoriasis. OBJECTIVES: To determine whether concomitant 311-nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. METHODS: Ten patients (five women and five men; mean age 58years, range 48-66) with moderate to severe plaque-type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90mg subcutaneously depending on body weight (below or above 100kg) at weeks 0 and 4. Within 2days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311-nm UVB-based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6weeks. Treatment response was monitored weekly in terms of half-body PASI. RESULTS: Nine patients completed the study. Analysis of their data showed that 311-nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311-nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3-5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV-irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P=0·007). At week 12, this synergistic effect of 311-nm UVB was still apparent although not significantly so. CONCLUSIONS: Treatment with 311-nm UVB accelerates the clearance of psoriatic lesions in ustekinumab-treated patients.

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.

BACKGROUND: Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. OBJECTIVES: To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. METHODS: Data from a psoriasis registry (http://www.psoriasis-therapieregister.at) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5-methoxypsoralen (5-MOP; n = 32) and 8-methoxypsoralen (8-MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8-MOP and 5-MOP, respectively) and at week 12 for biologics. RESULTS: Intention-to-treat-as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post-hoc modified worst-case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. CONCLUSIONS: Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head-to-head studies of PUVA and biologics are warranted to confirm these observations.

An update on the diagnosis and management of psoriatic arthritis.

Psoriasis is a common inflammatory disease with complex genetic background affecting approximately 2-3% of the population in the Western hemisphere. Around 20% of psoriasis patients also suffer from psoriatic arthritis (PsA). The clinical spectrum comprises a wide variety of arthritic manifestations ranging from dactylitis, peripheral symmetric or asymmetric mono-, oligo-, and polyarticular arthritis, spinal disease and enthesitis. As psoriasis precedes PsA in 75-80% of affected patients, dermatologists might play a pivotal role in early diagnosis of the disease. Furthermore, magnetic resonance imaging (MRI) scanning and ultrasonography have improved the radiological diagnosis of peripheral PsA, psoriatic spondylarthropathy and enthesitis. Besides the traditional treatment of PsA the introduction of biologics has led to a significant improvement in the treatment of the disease. To further improve diagnosis, treatment and quality of life in our patients suffering from PsA an excellent interdisciplinary collaboration between dermatologists, radiologists and rheumatologists is a necessity of utmost importance.

In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. OBJECTIVES: In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. METHODS: Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). RESULTS: The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 ± 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 ± 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). CONCLUSIONS: The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening.

Confocal laser scanning microscopy-guided surgery for neurofibroma.

The neurofibromatoses comprise at least two separate genetic disorders with variable clinical features and an unpredictable course. The most common type, neurofibromatosis 1, is characterized by > or = 6 café-au-lait spots and the occurrence of neurofibromas, which may present as cutaneous, subcutaneous or plexiform lesions. Normally, excision of neurofibromas is only indicated in the presence of neurological symptoms, suspicion of malignancy or for exceptional cosmetic reasons. For a good functional and aesthetic result with the least danger of recurrence, the surgeon's goal is to excise as much tissue as necessary and as little tissue as possible. One of the main issues during the surgical procedure is to distinguish between neurofibroma and surrounding tissue. We report for the first time the use of confocal laser scanning microscopy to differentiate between neurofibroma and healthy skin.

Tinea capitis in early infancy treated with itraconazole: a pilot study.

BACKGROUND: Tinea capitis is the most common fungal infection of the scalp in childhood, but a very rare disorder in the first year of life. OBJECTIVE: To evaluate the efficacy, tolerability and safety of itraconazole in 7 children aged between 3 and 46 weeks (median: 36 weeks) suffering from tinea capitis caused by Microsporum canis. METHODS: Prospective case note study. In all patients KOH testing and fungal cultivation on Sabouraud dextrose agar were performed. RESULTS: 7 patients (5 girls and 2 boys) were included in the period between 2001 and 2008. The causative etiologic agent was Microsporum canis in all children. The patients received itraconazole 5mg/kg bodyweight daily for 3 to 6 weeks with no clinically side effects being noted. In all patients clinical and mycological cure could be achieved. CONCLUSION: Itraconazole proved to be a safe and effective treatment option for Microsporum canis induced tinea capitis in children in their first year of life.

Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept.

BACKGROUND: Some patients with plaque-type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful. OBJECTIVES: To investigate whether treatment with 311-nm ultraviolet (UV) B can improve the therapeutic response in patients treated with etanercept. METHODS: Four women and one man (mean age 57 years, range 48-66) with moderate to severe plaque-type psoriasis who had received standard treatment with etanercept 50 mg twice weekly for 6 weeks without Psoriasis Area and Severity Index (PASI) reduction of 75% or greater (of initial mean PASI of 16.0, range 15.4-20.4) were enrolled in the study. Starting at 6 weeks, 311-nm UVB treatment was given to a randomly selected body half (left or right, excluding the head) for another 6 weeks, while all patients continued receiving etanercept. The patients were monitored by half-body PASI at weekly intervals. RESULTS: During the 6-week irradiation regimen, 311-nm UVB significantly bolstered the therapeutic response in the patients on etanercept treatment. After 6 weeks of 311-nm UVB, the patients had a mean PASI on their UV-irradiated body halves of 1.6 (range 0.6-3.3) vs. 4.7 (range 1.4-8.6) on nonirradiated body halves (P = 0.0192, paired two-tailed t-test), compared with 10.7 (range 6-16.4) and 10.5 (range 5.2-16.4) at start of 311-nm UVB treatment. The overall mean PASI reduction from baseline (i.e. at etanercept start) was 89% vs. 68%, respectively (P = 0.0009 and P = 0.0088). CONCLUSIONS: Treatment with 311-nm UVB significantly accelerates and improves the clearance of psoriatic lesions in patients responding slowly to etanercept monotherapy.

Assessing melanoma risk factors: how closely do patients and doctors agree?

OBJECTIVES: Self-examination of the skin has been associated with a reduced risk of advanced melanoma, but self-assessment has corresponded imperfectly with clinical examination by a dermatologist, and shown only moderate accuracy in identifying individuals at risk. STUDY DESIGN: Population-based screening campaign in Styria, Austria. METHODS: One thousand two hundred and twenty-three Caucasians volunteered for a free skin assessment by a dermatologist. First, they answered a questionnaire in which they assessed their own melanoma risk factors, and they were subsequently examined by a dermatologist. Kappa agreements between the two assessments were calculated. RESULTS: The overall kappa agreements on the estimated number of naevi, the assessment of skin phototype and the perception of increased melanoma risk were 0.34 [95% confidence interval (CI) 0.30-0.37], 0.28 (95%CI 0.24-0.32) and 0.24 (95% CI 0.18-0.30), respectively. Kappa agreements below 0.40 are considered poor. Stratification by age and gender revealed slightly higher scores for subgroups on single items. CONCLUSIONS: Screening for melanoma should be population based and should not be limited to self-referrals since self-assessment for melanoma risk factors is inaccurate. Educational programmes must be developed to improve self-assessment and to target populations at risk.