Efficacy of a fixed combination of calcipotriol/betamethasone dipropionate topical gel in adult patients with mild to moderate psoriasis: blinded interim analysis of a phase IV, multicenter, randomized, controlled, prospective study

Background: Psoriasis is a common, chronic, inflammatory skin disease with the majority of individuals having limited disease, treated with topical medication. However, special attributes of topical treatments like galenic/cosmetic properties or an inconvenient treatment schedule may result in low preference for topical treatments. Hence, there is strong medical need for a topical medication, which is highly efficacious, easy-to-use and preferred by both physicians and patients. Objective: Blinded interim analysis with the purpose to assess efficacy of (both from the physician's and patient's perspective) and the patients' preference with a highly efficacious and easy-to-use fixed combination of calcipotriol/betamethasone dipropionate topical gel after 8 weeks of once daily treatment in a large patient population. Methods: In this phase IV, international, multicentre, randomized, controlled, prospective, parallel group study, adult patients with active, mild to moderate psoriasis despite previous topical psoriasis treatment, i.e. unsuccessful in the 8 weeks preceding study participation, are followed over 64 weeks. During the first 8 weeks the patients apply their medication once a day followed by a 56-weeks maintenance period according to SmPC. Blinded interim analysis of all patients included demographics, Physician's Global Assessment, the novel Patient's self Global Assessment (PsGA) and Patient Preference Questionnaire (PPQ). Results: 1795 patients were analysed. At week 8, 36.5% of the physicians rated the patients' psoriasis as clear/almost clear. Similarly, based on the patients' self-assessment, 34.2% had a clear/almost clear score of PsGA in week 8. Analysis of the PPQ showed that the vast majority of the patients judged their 8-week treatment to be preferable compared with their previous treatments. Conclusion: Results of this blinded interim analysis indicate that the fixed combination of calcipotriol/betamethasone dipropionate gel is highly efficacious and preferred by the majority of analysed patients

Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate‐to‐severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2)

SummaryBackground Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines

Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters

BACKGROUND: Sarcoidosis is a multisystem disease of unknown origin characterized by the formation of noncaseating granulomas, in particular in the lungs, lymph nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used for large disfiguring lesions, generalized involvement, or recalcitrant lesions that did not respond to topical therapy. CASE PRESENTATIONS: We report three patients with recalcitrant cutaneous sarcoidosis who were treated with oral fumaric acid esters (FAE). Three female patients presented with cutaneous sarcoidosis that have proved to be refractory to various therapies, including corticosteroids and chloroquine. We treated the patients with FAE in tablet form using two formulations differing in strength (Fumaderm(® )initial, Fumaderm(®)). Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients. After treatment with FAE (4–12 months), a complete clearance of skin lesions was achieved in the three patients. The side effects observed in this trial correspond to the well-known spectrum of adverse effects of FAE (flush, minor gastrointestinal complaints, lymphopenia). CONCLUSIONS: On the basis of our findings FAE therapy seems to be a safe and effective regimen for patients with recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are necessary to confirm our preliminary results

A systematic review of factors associated with non-adherence to treatment for immune-mediated inflammatory diseases.

Background: Non-adherence impacts negatively on patient health outcomes and has associated economic costs. Understanding drivers of treatment adherence in immune-mediated inflammatory diseases is key for the development of effective strategies to tackle non-adherence. Objective: To identify factors associated with treatment non-adherence across diseases in three clinical areas: rheumatology, gastroenterology, and dermatology. Design: Systematic review Data sources: Articles published in PubMed, Science Direct, PsychINFO and the Cochrane Library from 1 January 1980 to 14 February 2014. Study selection: Studies were eligible if they included patients with a diagnosis of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, or psoriasis and included statistics to examine associations of factors with non-adherence. Data extraction: Data were extracted by the first reviewer using a standardised 23-item form and verified by a second/ third reviewer. Quality assessment was carried out for each study using a 16-item quality checklist. Results: 73 studies were identified for inclusion in the review. Demographic or clinical factors were not consistently associated with non-adherence. Limited evidence was found for an association between non-adherence and treatment factors such as dosing frequency. Consistent associations with adherence were found for psychosocial factors, with the strongest evidence for the impact of the healthcare professional-patient relationship, perceptions of treatment concerns and depression, lower treatment self-efficacy and necessity beliefs, and practical barriers to treatment. Conclusions: While examined in only a minority of studies, the strongest evidence found for non-adherence were psychosocial factors. Interventions designed to address these factors may be most effective in tackling treatment non-adherence

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

Non-adherence to medication is a challenging problem in daily clinical practice. To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. The DACH cohort had significantly different levels of adherence depending on the IMID (P &lt; 0.05) and the type of therapy (P &lt; 0.05). Based on the significant influence of concerns on treatment adherence (P &lt; 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups