Secukinumab is effective in treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and safety from the PROSPECT study.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate-to-severe psoriasis. Trial protocols specify transition periods and prohibit concomitant psoriasis medication. Data are therefore needed on secukinumab effectiveness and safety in routine clinical practice. OBJECTIVES: The PROSPECT study assesses prior and concomitant psoriasis treatments and transition periods in subjects receiving secukinumab. Here, we report interim effectiveness and safety data for secukinumab in the context of prior and concomitant treatments. METHODS: PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate-to-severe psoriasis with a decision to receive secukinumab 300 mg were included. RESULTS: Of 1988 subjects, 1238/1988 (62.4%) were male, and mean age was 48.1 ± 13.7 years. Mean baseline Psoriasis Area and Severity Index (PASI) score was 17.7 ± 12.5. 90.9% of subjects had prior systemic treatment. Concomitant treatment was recorded in 44.3% of subjects. Median duration of transition period was 14.0, 30.0 and 44.5 days from prior topical, conventional systemic and biologic treatments. At Week 24, PASI75/90/100 was reached by 86.1%, 68.5% and 39.7% of subjects who started secukinumab treatment at baseline. No unexpected safety signals were observed. CONCLUSION: PROSPECT provides a large prospective real-world analysis of secukinumab treatment and includes prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. Secukinumab effectiveness and safety were comparable to that seen in the phase 2/3 secukinumab clinical trial programme.

Secukinumab treatment of moderate to severe plaque psoriasis in routine clinical care: real-life data of prior and concomitant use of psoriasis treatments from the PROSPECT study.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe psoriasis. However, as per study protocols, transition periods from prior psoriasis treatments of a defined minimal length were required and use of concomitant psoriasis medication was prohibited. There is therefore a lack of data on the effect of shorter transition periods and concomitant psoriasis treatment with other pharmacologically active substances on the effectiveness and safety of secukinumab in routine clinical practice. OBJECTIVES: The PROSPECT study was designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab and the duration of transition periods from prior treatments to secukinumab. Here, we report the baseline characteristics and the duration of transition period in an interim analysis of the first 805 subjects. METHODS: PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate to severe psoriasis with a decision to receive secukinumab were included. RESULTS: The majority of subjects were male (491/796, 61.7%), with a mean age of 47.7 years (SD 13.7). The baseline Psoriasis Area and Severity Index (PASI) was available for 92.4% (744/805) of subjects, and mean baseline PASI was 17.5 (SD 13.1); 93.4% (752/805) of subjects had signs of high disease severity. Use of concomitant treatment increased with the number of signs. Within the last 12 months prior to inclusion, 10%, 40%, and 28% of subjects had received topical, conventional systemic, or biologic treatments as their last prior psoriasis therapy, respectively, and 22% of subjects had not received any psoriasis therapy. Discontinuation of prior treatment due to adverse events was high in subjects with conventional systemic treatment (93/413, 22.5%) compared to biologic treatment (5/210, 2.4%). The median duration of the transition period was 14.0, 30.5, and 38.0 days for prior topical, conventional systemic, and biologic treatments, respectively. CONCLUSION: PROSPECT is the first study to investigate prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. The majority of the subjects had a high disease burden and use of concomitant treatment increased with disease severity. The duration of the transition period depended on prior treatment.

[Treatment of granulomatous cheilitis with fumaric acid esters in a young woman]. / Fumarsäureestertherapie bei einer jungen Patientin mit ausgeprägter Cheilitis granulomatosa.

Granulomatous cheilitis is a rare granulomatous inflammation of the lips of unknown origin; mainly young adults are affected. So far, there is no generally effectual treatment available for this disfiguring dermatosis. We show the efficacy of a treatment with fumaric acid esters reporting the case of a 14-year-old girl with granulomatous cheilitis resistant to previous therapy. Our successful therapy consisted of fumaric acid esters according to the therapeutic schedule for psoriasis and showed a good tolerance subjectively and objectively.

[Promoting reading and spelling in children with computer programs]. / Lese- und Rechtschreibförderung von Kindern durch Computerprogramme.

OBJECTIVES AND METHODS: Sixteen students trained their reading and spelling skills with the computer programmes Budenberg 1 and 2 and the Comles Package for 1000 minutes over a one-month period. RESULTS: Following one month of computer training, reading test scores had improved for seven of the 16, and spelling test scores for three children whose basic performance had been poor. Three and a half months of school instruction later, the reading test scores had improved for nine children, while there was no effect upon the spelling scores for most of the students.

Comparison of severity scoring of atopic dermatitis values and serum levels of eosinophil cationic protein and mast cell tryptase for routine evaluation of atopic dermatitis.

In this study the routine use of different parameters for evaluation of the overall therapeutic outcome in atopic dermatitis was investigated. The disease activity of 117 randomly selected hospitalized patients suffering from atopic dermatitis was routinely assessed using the Severity Scoring of Atopic Dermatitis (SCORAD) index on admission and at discharge. Serum levels of eosinophil cationic protein and mast cell tryptase were determined in parallel both on admission and at discharge. After a mean treatment period of 24+/-12 days a decrease in the SCORAD index from 47.6+/-19.5 to 7.7+/-8.2 was achieved (p<0.001). Serum levels of eosinophil cationic protein decreased from 22.8+/-19.7 microg/l to 15.4+/-17.5 microg/l, whereas serum tryptase levels did not change. However, there was no significant correlation between the changes in SCORAD, eosinophil cationic protein and tryptase in our cohort. Thus, routine determination of serum eosinophil cationic protein or tryptase levels, in addition to evaluation of disease activity using the SCORAD index, is not recommended in unselected patients with atopic dermatitis.

In vitro investigations with the histamine H1 receptor antagonist, epinastine (WAL 801 CL), on isolated human allergic effector cells.

OBJECTIVE AND DESIGN: Skin mast cells, basophils and eosinophils are effector cells of acute and subacute allergic responses due to their capacity to produce a large number of (pro)inflammatory mediators. Histamine H1 receptor antagonists, such as epinastine (WAL 801 CL), have been described to partially exert antiallergic and antiinflammatory effects both in vivo and in vitro in addition to their antihistaminergic properties. The aim of the present study was to investigate whether epinastine could influence the in vitro activation of isolated human skin mast cells, basophils and eosinophils induced by different secretagogues. METHODS: Cells were isolated from healthy women following plastic surgery and healthy blood donors, respectively. Mast cells were isolated by enzymatic digestion of the skin. Blood cells were isolated by gradient centrifugation and negative selection with magnetic beads. RESULTS: A wide range of concentrations of the drug (1 nmol/l to 100 micromol/l) did not significantly inhibit histamine release from basophils induced by immunologic (anti-IgE, concanavalin A, priming factors interleukin-3 and interleukin-5) and non immunologic (A23187, ionomycin, 12-o-tetradecanoyl-phorbol-13-acetate, C5a, formyl-methionyl-leucyl-phenylalanine) stimuli. Furthermore, the drug had no effect on A23187-induced release of eosinophil cationic protein from eosinophils. However, at a concentration >0.1 nmol/l, IgE-mediated LTC4 production from basophils was significantly suppressed. Histamine release from skin mast cells due to anti-IgE or A23187 was inhibited by epinastine in a dose-dependent fashion, whereas substance P-induced activation as well as stem cell factor priming were not. Epinastine did not inhibit isolated protein kinase C from rat brain. CONCLUSION: The results confirm previous in vivo and in vitro observations obtained from animal models that epinastine exerts antiallergic and antiinflammatory effects. Whether the observed effects are due to non specific membrane interactions or by influencing intracellular signal transduction elements has to be further elucidated.

[Effects of combined dermatological and behavioural medicine therapy in hospitalized patients with psoriasis and atopic dermatitis]. / Effekte kombinierter therapeutischer Massnahmen bei Patienten mit Psoriasis und atopischer Dermatitis.

The present study examined the effectiveness of combined dermatological and behavioural medicine therapy on the skin status and disease-specific stress of eighty-six patients with psoriasis and fifty-eight patients with atopic dermatitis who were hospitalized in the PsoriSol Clinic, Hersbruck, Germany. In addition to receiving instruction about their stain disease, the patients were offered, practice in relaxation techniques, social contacts and scratching control as well as individual psychological counselling. The clinical change was assessed by PASI and SCORAD, respectively. The Marburg questionnaire for coping with skin diseases (MHF) and a questionnaire for health-related control attributes (GKU-S) served as psychometric measures. Patients showed significant improvement in skin status and psychosocial parameters in pre-post comparison. Social fears, avoidance and helplessness were reduced by significant improvement of the emotional status in both groups. Patients with psoriasis also showed an increase in internal control attributes. Dermatological treatment combined with behavioural medicine therapy can be considered an effective method in patients with atopic dermatitis and psoriasis.

[Quality of life in skin diseases: methodological and practical comparison of different quality of life questionnaires in psoriasis and atopic dermatitis]. / Lebensqualität bei Haut- erkrankungen: Vergleich verschiedener Lebensqualitäts-Fragebögen bei Psoriasis und atopischer Dermatitis.

Aim of the present study was a comparison of four quality of life (QoL) questionnaires in 228 patients with psoriasis (PSO, n = 148) and atopic dermatitis (AD, n = 80) regarding feasibility, discriminant validity and sensitivity to change. Evaluating were performed before and after treatment in clinic. The following questionnaires were compared. 1) Freiburg Quality of Life Assessment for Dermatoses (FLQA-d), 2) Dermatology Life Quality Index (DLQI), 3) Chronic Skin Disease Questionnaire (CSDQ) and 4) questionnaire on everyday life (ALLTAG). All questionnaires were able to discriminate significant reductions of QoL in PSO and AD, as compared to controls. In parallel to the clinical improvement, all questionnaires showed QoL improvements as well, i.e. the questionnaires were sensitive to change. However, not all of the DLQI and ALLTAG scales were sensitive to change. Also, in some cases part of the scales of these questionnaires could not be calculated due to missing data. Otherwise, all questionnaires were valid and easy to handle. Thus, QoL of patients with PSO and AD can reliably be assessed by various questionnaires. Decisive for selection are the aim and the design of the study.

Enteral histaminosis: Clinical implications.

There is increasing evidence that enteral histaminosis is a major cause of food intolerance resulting from dysfunctional metabolism of endogenous histamine in certain food stuffs. However, this phenomenon has been poorly characterised and, due to the lack of epidemiological data, the existence of this condition has been underestimated, which may lead to incorrect diagnosis. This short commentary highlights a stricter regimen of diagnostic procedure in order to take into account the many causes of food intolerance. The underlying mechanisms ascribed particularly to non-immunologically food reactions require more rigorous research and further work is vital.

[Quality management in the German health care system]. / Qualitätsmanagement im deutschen Gesundheitswesen.

With the increasing demands on hospitals for improved quality and lower costs, hospitals have been forced to reevaluate their manner of operation and quality assurance programs. Hospitals have also been faced with customer dissatisfaction and intense competition. This article reviews current quality-management systems and examines their position in dermatology.

[The "Hersbruck Model". Application and integration of the DIN EN ISO 9001 quality norms with criteria of the European Foundation for Quality Management in a clinic]. / Das "Hersbrucker Modell". Anwendung und Verknüpfung der Qualitätsnorm DIN EN ISO 9001 mit Kriterien der European Foundation for Quality Management in einer Klinik.

The german health system has dramatically changed and still continues to do so. Modified aspects concerning economy, customer orientation, competition, quality assurance and quality management seem to be increasingly important. Appropriate response to this challenge demands a relevant adjustment of a quality "philosophy" within a hospital. The "Hersbruck Model" has proven to be a suitable approach: on the basis of a quality management system--established and certified according to DIN EN ISO 9001--it implements all components of the model of the European Foundation for Quality Management. The modern quality tools as Total Quality Management and continuous quality improvement allow a permanent increase of customer/patient satisfaction.

Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Frühblühermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P<0.001); IgE was not significantly different. Eosinophil cationic protein remained unchanged with STI, but significantly increased with placebo in the pollen season (P=0.003). STI was well tolerated. In conclusion, STI was shown to be efficacious and safe for the treatment of patients with tree-pollen rhinoconjunctivitis.

Inhibition of interleukin-4 and interleukin-13 release from immunologically activated human basophils due to the actions of anti-allergic drugs.

Human basophils have recently been shown to rapidly produce and release interleukin (IL-)4 and IL-13 as well as histamine and eicosanoids. Since both IL-4 and IL-13 can initiate and maintain late phase allergic reactions we addressed whether some widely used anti-allergic drugs can inhibit the anti-IgE induced release of these cytokines from enriched human basophils. Basophils were enriched (47-92% purity) by Ficoll density centrifugation followed by elutriation and negative selection of contaminating cells using immunomagnetic beads. Basophils were stimulated with sub-optimal dilutions of anti-IgE in the presence or absence of various drugs and the release of histamine and cytokines were measured after 30 min and 4 h, respectively. The beta-2 agonist salmeterol, the H1-receptor antagonist terfenadine and the phosphodiesterase inhibitor theophylline inhibited the release of IL-4 and IL-13 by more than 50% following 4 h of basophil stimulation with anti-IgE. These drugs also inhibited the release of histamine following 30 min stimulation, although with less efficacy than for IL-4 and IL-13. Short preincubation of basophils with salmeterol or terfenadine before stimulation gave rise to significantly greater inhibition of histamine release but had less effect on the inhibition of cytokine release. The effects of theophylline, however, were not significantly affected by preincubation of the cells with the drug. In contrast to the aforementioned drugs, salbutamol and cetirizine were ineffective at inhibiting both histamine and cytokine release from basophils. These results suggest that a number of anti-allergic drugs may mediate their effects, in part, in reducing late phase allergic responses due to their actions on IL-4 and IL-13 secretion from basophils.

[Pathophysiologic and immunologic mechanisms of contrast medium-induced anaphylactoid immediate hypersensitivity--an overview]. / Pathophysiologische und immunologische Mechanismen kontrastmittelinduzierter anaphylaktoider Sofortreaktionen--eine Ubersicht.

Since non-ionic radiocontrast media (RCM) have been introduced, the incidence of unwanted reactions has been significantly reduced in comparison to ionic compounds. However, acute anaphylactoid reactions with heterogenous symptoms within minutes after intravasal application are still a life-threatening risk of investigations with RCM. The present article summarizes the current view of the underlying pathomechanisms of such reactions.

A three-step procedure for the purification of human basophils from buffy coat blood.

OBJECTIVE AND DESIGN: We report a method for basophil purification from buffy coats, which avoids positive selection of the cells and gives rise to good purity, yield and functional integrity of the cells. SUBJECTS: Buffy coat blood (concentrated leukocyte fraction derived from 450 ml venipuncture donations) obtained from healthy blood donors (n = 51). METHODS: Basophils were enriched by a three-step process starting with Ficoll density centrifugation (1.6 +/- 0.1% basophil purity) followed by counter current centrifugal elutriation (17.7 +/- 1.4% basophil purity). The final stage involved negative selection using Dynal immunomagnetic beads directed against CD2, CD14, CD16 and CD19 positive cell contaminants. Functional integrity of which was assessed by comparing the anti-IgE or calcium ionophore A23187 induced histamine release from basophils obtained from each enrichment step. Furthermore, basophil morphology was investigated using light and electron microscopy. RESULTS: The final mean basophil purity of 67.3 +/- 1.4% with a yield of 3.5 +/- 0.5 x 10(6) basophils and a recovery of 21.8 +/- 2.4% was achieved. Net histamine release from basophils stimulated with optimal concentrations of anti-human IgE was 39.1 +/- 6.5% after Ficoll centrifugation, 41.6 +/- 7.7% following elutriation and 35.7 +/- 6.8% from the final purified fraction. Additionally, basophils enriched with our method showed intact morphology by electron microscopy and were functionally active to non-immunological stimulation. CONCLUSIONS: These results compare favourably with previous studies, which have often required the use of positive selection via the Fc epsilon RI receptor, which may result in cell degranulation, or cell sorting, which cannot be applied to large cell numbers. Our method provides a reproducible technique for basophil enrichment when large numbers of functionally intact basophils are required.