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Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. To evaluate the implementation of protocolized biologic DR in daily practice. A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR. [ABSTRACT FROM AUTHOR]

Background: Genetic predictors for treatment response could optimize allocation of biological treatment in patients with psoriasis. There is minimal knowledge about pharmacogenetics of anti‐IL‐17 agents. Objectives: To assess whether genetic variants in the protein‐coding region or untranslated regions of the IL‐17A gene are associated with response to IL‐17A inhibitors in patients with psoriasis. Methods: This was a multicenter European cohort study investigating pharmacogenetics of IL‐17A inhibitors in patients with psoriasis. Patients with plaque psoriasis treated with secukinumab or ixekizumab in daily practice were included. For all participants, the protein‐coding region and untranslated regions of the IL‐17A gene were analysed using Sanger sequencing. Identified genetic variants were tested for association with response to secukinumab/ixekizumab, measured as ∆PASI, after 12 weeks (primary outcome) and after 24 weeks (secondary outcome). Association was tested using a linear regression model with correction for baseline PASI as a fixed covariate and for biological naivety and body mass index as additional covariates. Results: In total, 134 patients treated with secukinumab or ixekizumab were included. Genotyping of the cohort identified genetic variants present in untranslated regions and intronic DNA, but not in the protein‐coding region of the IL‐17A gene. Five genetic variants in non‐coding DNA with a known or suspected functional effect on IL‐17A expression were selected for association analyses: rs2275913, rs8193037, rs3819025, rs7747909 and rs3748067. After 12 weeks, 62% of patients achieved PASI75 and 39% achieved PASI90. At week 24, PASI75 and PASI90 response rates were 72% and 62%, respectively. No associations were found between the five genetic variants and ∆PASI, PASI75 or PASI90 after 12 and 24 weeks of anti‐IL‐17A treatment. Conclusions: Response to IL‐17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein‐coding and untranslated regions of the IL‐17A gene. Pharmacogenetics of IL‐17A inhibitors in the treatment of psoriasis requires further exploration. Linked Commentary: K. Eyerich J Eur Acad Dermatol Venereol 2020; 34: 11–12. https://doi.org/10.1111/jdv.16047. [ABSTRACT FROM AUTHOR]

Background It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. Objectives To assess the number of treatment episodes ( TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index ( PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. Methods Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni- and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. Results In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index ( BMI) were significant predictors for PASI ≤ 5 at week 24. Conclusions A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response. [ABSTRACT FROM AUTHOR]

Background Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different biologics or for the reason of discontinuation. Objectives To compare long-term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side-effects for each biologic separately. Methods Ten years of data were extracted from the prospective, multicentre, long-term Bio CAPTURE registry. Kaplan-Meier survival analyses and confounder-corrected multivariate Cox regression analysis for drug survival ( MCR- DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors ( MCR-P) with backward selection were performed. Results In total, 526 treatment episodes - 186 adalimumab, 238 etanercept and 102 ustekinumab - were included covering 1333 treatment years. MCR- DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR-P showed that higher body mass index ( BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side-effects for adalimumab, etanercept and ustekinumab. Conclusions Ustekinumab has the highest confounder-corrected long-term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics. [ABSTRACT FROM AUTHOR]

Background Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. Objectives (I) To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Methods Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. Results One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities ( P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender ( P = 0.02). Conclusions Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment. [ABSTRACT FROM AUTHOR]

Background Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. Objectives (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index ( DLQI) ≤ 5 combined with being 'on drug' at a specific time point. Methods Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' ( DLQI ≤ 5) vs. 'unhappy' ( DLQI > 5) at baseline and months 3, 6, 9 and 12. Results 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio ( HR) 3·8, P = 0·02] and a trend towards better survival vs. adalimumab ( HR 2·3, P = 0·1). At baseline, the majority ( n = 115, 73%) was considered 'unhappy' and a minority 'happy' ( n = 42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. Conclusions Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success. [ABSTRACT FROM AUTHOR]

Background Although the effectiveness of biologics for psoriasis has been measured extensively with objective outcome measures, studies based on subjective, patient-reported outcome measures remain scarce. Objectives To investigate satisfaction with medication, as measured by the Treatment Satisfaction Questionnaire for Medication ( TSQM) for biologics in daily practice psoriasis care in the first 6 months of treatment; and to identify possible differences in satisfaction with medication between patients experienced (biologics-experienced) and inexperienced (biologics-inexperienced) in the use of biologics. Methods TSQM baseline measurements were compared using measurements taken after 6 months, using the Wilcoxon signed-rank test for paired comparisons. Intention-to-treat with last observation carried forward (ITT with LOCF) and as-treated analyses were performed. The difference between biologics-experienced and biologics-inexperienced patients for TSQM was analysed using ITT with LOCF. At 6 months, outcomes for biologics-experienced and biologics-inexperienced patients were compared using the Mann-Whitney U-test. Results One hundred and six patients were eligible for analysis, and treated with etanercept ( n = 34), adalimumab ( n = 49) or ustekinumab ( n = 23). Fifty-four per cent of patients were biologics-inexperienced. A statistically significant improvement was seen in all domains of the TSQM ('effectiveness', 'side-effects', 'convenience' and 'global satisfaction') by comparison of months 3 or 6 with baseline (all P ≤ 0·02). After 6 months, biologics-inexperienced patients scored better on the 'global satisfaction' domain than biologics-experienced patients ( P < 0·01). Conclusions We provide a prospective, longitudinal analysis of TSQM for biologics in daily practice psoriasis care. High satisfaction rates were achieved. The 'effectiveness' and 'convenience' domains showed the most room for improvement. [ABSTRACT FROM AUTHOR]