Secukinumab treatment in new-onset psoriasis: aiming to understand the potential for disease modification - rationale and design of the randomized, multicenter STEPIn study.

BACKGROUND: To date, biological treatments have been assessed in subjects with a long-term history of psoriasis and previous failures to systemic and topical therapies. In rheumatoid arthritis and other immune-mediated inflammatory diseases, early intensive systemic treatment prolongs treatment-free remission. We hypothesize that, by treating patients with psoriasis early with an effective systemic therapy, we may be able to alter the clinical outcome and the natural course of the disease. The STEPIn study (NCT03020199) investigates early intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB) phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine whether early intervention with either nb-UVB treatment or secukinumab in subjects with new-onset plaque psoriasis might modify the natural course of the disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset (≤12 months) moderate-to-severe plaque psoriasis and naïve to systemic treatment and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week break between cycles). After treatment discontinuation, patients will be followed up and monitored for disease activity up to Week 208. A Mechanistic Sub-study will assess immunological changes and pathogenic tissue-resident memory T cells in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

Sunscreen use: controversies, challenges and regulatory aspects.

Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight.

Determination of immunoglobulin G in bovine colostrum and milk powders, and in dietary supplements of bovine origin by protein G affinity liquid chromatography: collaborative study.

An AOAC collaborative study was conducted to evaluate an affinity LC procedure for measuring immunoglobulin G (IgG) in selected dairy powders. The powders were extracted with 0.15 M sodium chloride solution and the pH was adjusted to 4.6 to precipitate caseins, which would otherwise lead to an overestimation of IgG. The analyte was then bound to a commercially available Protein G affinity cartridge and selectively eluted with a glycine buffer at pH 2.5. Detection was at 280 nm and quantification was made against a calibration curve prepared from bovine serum IgG. The samples analyzed included the likely matrixes for which this assay will find commercial use, namely, high- and low-protein-content colostrum powders, tablets containing colostrum powder, and some IgG-containing dairy powders; milk protein isolate, whey protein concentrate, and skim milk powder. Eleven laboratories provided data for the study and assayed blind duplicates of six materials. The repeatability RSD values ranged from 2.1 to 4.2% and the reproducibility RSD values ranged from 6.4 to 18.5%. The Protein G method with casein removal has adequate reproducibility for measuring IgG in colostrum-derived powders that are traded on the basis of IgG content as a colostral marker.

Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis. OBJECTIVE: The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here. METHODS: Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). RESULTS: There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025). CONCLUSION: There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.

A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris.

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product Dovobet/Daivobet/Taclonex(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time. OBJECTIVES: To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis. METHODS: Patients (n = 634) were randomized double-blind to treatment with: (i) 52 weeks of the two-compound product (two-compound group); (ii) 52 weeks of alternating 4-week periods of the two-compound product and calcipotriol (alternating group); or (iii) 4 weeks of the two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). Treatments in all groups were used once daily when required. RESULTS: Adverse drug reactions (ADRs) occurred in 45 (21.7%) patients in the two-compound group, 63 (29.6%) in the alternating group and 78 (37.9%) in the calcipotriol group. The odds ratio for an ADR in the two-compound group relative to the calcipotriol group was 0.46 (95% confidence interval 0.30-0.70; P < 0.001). ADRs of concern associated with long-term topical corticosteroid use occurred in 10 (4.8%) patients in the two-compound group, six (2.8%) in the alternating group and six (2.9%) in the calcipotriol group; those with the highest incidence were skin atrophy, occurring in four (1.9%), one (0.5%) and two (1.0%) patients, respectively, and folliculitis, in three (1.4%), one (0.5%) and no patients, respectively. CONCLUSIONS: Treatment with the two-compound product for up to 52 weeks appears to be safe and well tolerated whether used on its own or alternating every 4 weeks with calcipotriol treatment.

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.

BACKGROUND: Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. OBJECTIVES: To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. METHODS: Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas. RESULTS: Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect. CONCLUSIONS: Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

[Treatment of psoriasis in general practice]. / Behandling av psoriasis i allmennpraksis.

Psoriasis is a chronic skin disease which affects about 2% of the population. Several new treatment modalities have been introduced in recent years. This article focuses on topical treatment of mild and moderate psoriasis that can be successfully treated at home. It is important that general practitioners who treat most of these patients are familiar with the best treatment procedures. Phototherapy and systemic therapy, mainly by dermatologists, are described in brief.

[Nevus flammeus in small children treated pulsed dye laser]. / Nevus flammeus hos små barn behandlet med pulset fargelaser.

We report the results of treating 30 children less than 7.5 years old for port wine stains of the face and neck using pulsed dye laser with a wave length of 585 nm. The children were given a general anaesthetic. In five children the stains disappeared completely and in 21 there was marked improvement (> 75% lighter). The younger age group, 7 months to 4 years, required fewer treatment sessions (mean 3.7) than the older age group, 4 to 7 years (mean 5.1 sessions), indicating the benefit of early treatment. No side effects were seen except for transient hyperpigmentation.

[Dermatomyositis and cancer. A retrospective study]. / Dermatomyositt og kreft. En retrospektiv undersøkelse.

In a retrospective study, the files of 19 patients with dermatomyositis examined at our departments from 1970 to 1993 were reviewed. The parameters studied were age, sex, muscle enzyme values, muscle biopsies, electromyographical findings and interval from onset of dermatomyositis until first visit to the department. Out of 19 patients with dermatomyositis, 18 were adults and in nine of these the condition was associated with cancer (three out of three men, six out of 15 women). Electromyographical findings were pathological in 17 investigated patients and myositis was indicated in 13 out of 15 biopsies. Muscle enzyme values were elevated in seven out of nine patients with cancer and in three out of nine without. Out of five patients with dysphagia, four patients had cancer. The risk of cancer is increased in patients with dermatomyositis. Factors indicating a poor prognosis regarding the association between dermatomyositis and cancer in our study were old age, male sex and dysphagia.

[New treatment of psoriasis with the vitamin D analogue calcipotriol]. / Ny behandling av psoriasis med D-vitaminanalogen calcipotriol.

A new topical treatment for psoriasis was introduced in 1992 when the vitamin D analogue calcipotriol was registered in Norway. This is a new therapeutic principle for psoriasis. Calcipotriol induces differentiation and inhibits proliferation of the keratinocytes. Application twice daily for 6-8 weeks gives a 60-70% improvement in plaque type psoriasis. No serious side effects have been reported when using up to 100 grams of the ointment weekly.

Blue rubber bleb nevus syndrome with manifestations in the vulva.

The blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder, manifesting with hemangiomas which are usually located in the gastrointestinal tract and/or in the skin. These lesions can cause local, sometimes severe bleedings or cosmetic problems. This report describes a young woman with BRBNS manifestations on the buttocks and in the vulva, the latter giving rise to symptoms specific to this location. The blood-filled blebs were successfully treated by argon laser. As far as we know, manifestations of this disease in the female genital tract have not previously been described.

Efficacy and skeletal side effects of two years' acitretin treatment.

In this prospective study, 51 patients suffering from psoriasis and ichthyosis were treated with acitretin for 2 years. The average dose was 0.5 mg/kg/day. We have evaluated the efficacy and side effects, focusing on skeletal side effects. X-ray examinations were done before treatment and after 1 and 2 years. Forty-five patients completed the study. Acitretin had a good clinical effect, with 75% improvement in 35 of the patients. Apart from the well-known side effects affecting the mucous membranes, one patient developed biopsy- proven toxic hepatitis. In 2 patients we observed unusual skeletal calcifications located in the forearms and in the hip. These were considered to be caused by the drug. In this study, which included patients up to 71 years, only radiographs of the pelvis and the forearms were of value as routine follow-up films.

Hereditary haemorrhagic teleangiectasia: unsuccessful treatment with the flashlamp-pulsed dye laser.

In seven patients with hereditary haemorrhagic teleangiectasia (HHT) only one patient had lasting benefit from treatment with the flashlamp-pulsed dye laser. In seven other patients who had received other treatment before, none had any observable effect of this laser. The flashlamp-pulsed dye laser therefore does not seem to be effective in the treatment of nasal teleangiectasias.

An open, parallel groups, study of the importance of thoroughness of application in the treatment of psoriasis with a dithranol cream (Micanol).

Earlier studies have suggested that the rate of healing is somewhat slower for the new microencapsulated dithranol formulation, Micanol, than for petrolatum or paraffin based formulations. The less smeary Micanol formulation may need more vigorous application. A population of 29 patients with chronic, stable plaque-type psoriasis was divided into two groups, both receiving short contact treatment. One group received standard patient information while the other received information stressing the importance of being thorough when rubbing the dithranol cream into the lesions. Regarding composite sign severity score, there was a significant difference (about 50%) in favour of the extra information group after 6 weeks. This result suggests that thoroughness of application is an important factor for the rate of healing in short contact treatment of psoriasis with Micanol.