Evaluation of therapeutic benefits from the patient's perspective is important in medical decision-making and reimbursement. This study aimed at developing and validating an instrument on patient-defined needs and benefits in dermatology. The questionnaire was developed according to international guidelines. The benefit assessment consists of two steps: before treatment, every patient defines his treatment needs according to a standardized list. After treatment, the patient rates the degree of benefits achieved. A "patient benefit index" (PBI) is calculated by averaging the preference-weighed results of all items. The PBI questionnaire was validated in a sample of 500 patients with ten skin diseases and in a treatment study on 906 patients with acne. The patients defined a broad spectrum of needs and treatment benefits, indicating disease-specific patterns. The PBI showed good feasibility, reliability (Cronbach's alpha >0.91) and construct validity, high responsiveness, and discrimination between subgroups. The PBI permits valid evaluation of patient-relevant benefits in dermatological treatment.

Background: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-tosevere psoriasis. Methods: In this prospective, double-blind, multicentre phase 3 study (METOP) eligible patients were 18 years or older with a diagnosis of chronic plaque psoriasis at least 6 months before baseline, had a psoriasis area and severity index (PASI) of 10 or more or 10% or greater body-surface area involvement or a dermatology life quality index (DLQI) of 10 or more and were naïve to treatment with MTX. Participants were randomly assigned 3:1 by computer-generated random sequence integrated in the electronic data capture system to receive either MTX at a starting dose of 17.5 mg/week or placebo for the first 16 weeks, followed by openlabel MTX treatment of all patients up to 52 weeks (MTX/MTX and PLC/MTX groups, respectively). Dose escalation to 22.5 mg/week was allowed after 8 weeks of MTX therapy if patients failed to achieve an at least 50% improvement of their baseline PASI (PASI50); blinding was maintained by a corresponding volume increase of placebo injections. Treatment was combined with folic acid 5 mg/week. The primary efficacy endpoint was the proportion of patients achieving a PASI75 response at week 16 analysed by intention to treat with non-responder imputation. This study is registered with the European Medicines Agency, EudraCT number 2012-002716-10. Findings: Between February 2013 and May 2015 120 patients were randomly assigned to receive subcutaneous MTX (n=91) or placebo (n=29). The primary endpoint was met; the PASI75 response rate at week 16 was 41% (n=37) in the MTX group compared to 10% (n=3) in the placebo group [p=0.0026; effect size 30.3% (95% CI 15.3-45.3) MTX vs placebo]. Subcutaneous MTX was generally well tolerated; no cases of serious infections, malignancies, major adverse cardiovascular events or deaths were noted. Serious adverse events were observed in 3 patients started on MTX during the 52-week study period. Interpretation: The study documents a favourable 52-week benefit-risk profile of subcutaneous MTX in psoriasis. The route of administration and the intensified dosing schedule should be considered when using MTX in patients with psoriasis. Role of the funding source (see also below)The study was an investigator-initiated trial supported by a grant from Medac to K.R. Manuscript 2 SummaryBackground: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-to-severe psoriasis.

Psoriasis is a chronic, recurrent immune-mediated skin disease with a 2-3% prevalence in the Western population, which severely affects patients' quality of life and poses a considerable socioeconomic challenge. The majority of individuals have psoriasis in limited areas and topical products are the mainstay of therapy according to existing guidelines. It is known that medication adherence rates are lower for topical treatment than for systemic treatment.Poor medication adherence is a major multidimensional problem for patients with chronic disorders as it is associated with unfavourable treatment outcomes, increased risk for development of concomitant diseases and inefficient use of health resources. Despite four decades of adherence research and the large number of studies that have identified the importance of medication non-adherence, there are relatively few studies reporting and designing effective strategies to improve adherence. The aim of this article was to report and describe non-adherence in the topical treatment of psoriasis, the factors that might contribute to this phenomenon, and which interventions have so far been developed for the management of chronic conditions. This article proposes that given that the barriers to medication adherence are complex and varied, solutions to improve adherence and thus clinical outcomes must be multifaceted and must also provide the possibility to be tailored according to each patient's individual needs.Such an individualized and comprehensive adherence-enhancing intervention would probably enable the successful long-term management of this disabling chronic condition.

SummaryBackground Around two-thirds of patients with psoriasis do not adhere to topical treatment. The Topical Treatment Optimization Programme (TTOP), a fiveelement tool, includes guidance for the conversation between dermatologists/ nurses and patients, patient information material, telephone/e-mail helpdesks and treatment reminders. It has been developed by patients and dermatologists to help increase adherence to treatment in psoriasis. Objectives To compare TTOP with standard of care ('non-TTOP') within a large European investigator-initiated study, PSO-TOP (clinicaltrials.gov NCT01587755). Methods Patients with mild-to-moderate psoriasis received calcipotriol/betamethasone dipropionate gel as standardized study medication and were randomized 1 : 1 to either TTOP or non-TTOP management. Study medication was applied once daily for 8 weeks followed by 'as needed' application for an additional 56 weeks. Response was defined as a Physician's Global Assessment (PGA) of 'clear' or 'almost clear'. Results In 1790 patients (full analysis set), response rates after 8 weeks (primary objective) were significantly higher for TTOP (36Á3%) than for non-TTOP (31Á3%, P = 0Á0267). Better clinical outcome was accompanied by higher rates of patients feeling well informed about their skin condition, treatment and other factors related to adherence, but the Dermatology Life Quality Index was not statistically different. TTOP patients regarded the structured one-to-one conversations with their dermatologist/nurse as the most important element of TTOP. Conclusions Patients randomized to the TTOP intervention had a better clinical response than patients receiving standard of care. Improved communication between the healthcare provider and patient might be an important element in increasing adherence to topical therapy in psoriasis.

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