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Introduction The purpose of this study is to explore treatment preferences and identify patient characteristics in young bio-naive adults with moderate to severe psoriasis in the Nordic countries (Norway, Finland, Sweden, and Denmark). Methods Patients were 18–45 years old and bio-naive but referred for biologic treatment of moderate to severe psoriasis. Patients were included at eight Nordic dermatology clinics. Patients with significant comorbidity or psoriatic arthritis were excluded. The Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were assessed along with basic patient information. A semistructured interview guide was used in individual qualitative interviews, asking patients about their treatment preferences and reasons, disease journey, and disease management. The interviews were analyzed using thematic content analysis. Twenty-four patients sufficed to reach saturation in this qualitative study. Results The patient sample characteristics represented a qualitative variation in age, sex, symptoms, duration of disease, and country. We included a total of 12 male and 12 female patients. The mean age was 34 years (range 18–45 years), the mean age at diagnosis was 20 years (range 6–34 years), the mean ± standard deviation (SD) time since diagnosis was 13 ± 8 years, PASI was 9.5 ± 4.7, and DLQI was 15.2 ± 6.4. Interviews suggested that both the burden of disease as well as the burden of treatment influenced patient preferences regarding treatment attributes, hence getting alleviation from symptoms did not alone influence patient preferences. Time, effort, and inconvenience related to psoriasis treatments also influenced patient preferences. Conclusions This first in-depth, qualitative study in young bio-naive adults with psoriasis suggests that patient preferences are focusing not only on symptom relief but also on alleviating the burden of psoriasis treatment. Unders, Introduction: The purpose of this study is to explore treatment preferences and identify patient characteristics in young bio-naive adults with moderate to severe psoriasis in the Nordic countries (Norway, Finland, Sweden, and Denmark). Methods: Patients were 18–45 years old and bio-naive but referred for biologic treatment of moderate to severe psoriasis. Patients were included at eight Nordic dermatology clinics. Patients with significant comorbidity or psoriatic arthritis were excluded. The Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were assessed along with basic patient information. A semistructured interview guide was used in individual qualitative interviews, asking patients about their treatment preferences and reasons, disease journey, and disease management. The interviews were analyzed using thematic content analysis. Twenty-four patients sufficed to reach saturation in this qualitative study. Results: The patient sample characteristics represented a qualitative variation in age, sex, symptoms, duration of disease, and country. We included a total of 12 male and 12 female patients. The mean age was 34 years (range 18–45 years), the mean age at diagnosis was 20 years (range 6–34 years), the mean ± standard deviation (SD) time since diagnosis was 13 ± 8 years, PASI was 9.5 ± 4.7, and DLQI was 15.2 ± 6.4. Interviews suggested that both the burden of disease as well as the burden of treatment influenced patient preferences regarding treatment attributes, hence getting alleviation from symptoms did not alone influence patient preferences. Time, effort, and inconvenience related to psoriasis treatments also influenced patient preferences. Conclusions: This first in-depth, qualitative study in young bio-naive adults with psoriasis suggests that patient preferences are focusing not only on symptom relief but also on alleviating the burden of psoriasis treatment. Understanding the reasons for patient preferences and the pe

Background Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. Objectives The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. Methods The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. Results In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals.

The function of most lipases is controlled by the lid, which undergoes conformational changes at a water–lipid interface to expose the active site, thus activating catalysis. Understanding how lid mutations affect lipases’ function is important for designing improved variants. Lipases’ function has been found to correlate with their diffusion on the substrate surface. Here, we used single-particle tracking (SPT), a powerful tool for deciphering enzymes’ diffusional behavior, to study Thermomyces lanuginosus lipase (TLL) variants with different lid structures in a laundry-like application condition. Thousands of parallelized recorded trajectories and hidden Markov modeling (HMM) analysis allowed us to extract three interconverting diffusional states and quantify their abundance, microscopic transition rates, and the energy barriers for sampling them. Combining those findings with ensemble measurements, we determined that the overall activity variation in the application condition is dependent on surface binding and lipase mobility when bound. Specifically, the L4 variant with a TLL-like lid and wild-type (WT) TLL displayed similar ensemble activity, but WT bound stronger to the surface than L4, while L4 had a higher diffusion coefficient and thus activity when bound to the surface. These mechanistic elements can only be de-convoluted by our combined assays. Our findings offer fresh perspectives on the development of the next iteration of enzyme-based detergent.

The function of most lipases is controlled by the lid, which undergoes conformational changes at a water–lipid interface to expose the active site, thus activating catalysis. Understanding how lid mutations affect lipases’ function is important for designing improved variants. Lipases’ function has been found to correlate with their diffusion on the substrate surface. Here, we used single-particle tracking (SPT), a powerful tool for deciphering enzymes’ diffusional behavior, to study Thermomyces lanuginosus lipase (TLL) variants with different lid structures in a laundry-like application condition. Thousands of parallelized recorded trajectories and hidden Markov modeling (HMM) analysis allowed us to extract three interconverting diffusional states and quantify their abundance, microscopic transition rates, and the energy barriers for sampling them. Combining those findings with ensemble measurements, we determined that the overall activity variation in the application condition is dependent on surface binding and lipase mobility when bound. Specifically, the L4 variant with a TLL-like lid and wild-type (WT) TLL displayed similar ensemble activity, but WT bound stronger to the surface than L4, while L4 had a higher diffusion coefficient and thus activity when bound to the surface. These mechanistic elements can only be de-convoluted by our combined assays. Our findings offer fresh perspectives on the development of the next iteration of enzyme-based detergent.