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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: Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates. Objectives: To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM). Methods: Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily‐practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes. Results: We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for 'side‐effects' (P = 0.05) and 'global satisfaction' (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005). Conclusions: This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side‐effects and global satisfaction. Differences in treatment satisfaction and side‐effects might add to the fact that women discontinue biological treatments more often. [ABSTRACT FROM AUTHOR]

Background The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. Objectives We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. Methods We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms ( SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3 IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index ( PASI) was calculated as ∆ PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆ PASI corrected for baseline PASI, primary analysis) and Pearson's χ2-test or Fisher's exact test ( PASI 75, secondary analysis). Results We included 348 treatment episodes in 234 patients. Patients heterozygous ( GA) for the SNP in CD84 (rs6427528) had a better ∆ PASI response to etanercept after 3 months ( P = 0·025) than the homozygous reference group ( GG). In addition, patients heterozygous ( CT) for the IL12B variant showed a better response (∆ PASI) to ustekinumab ( P = 0·017) than the reference group ( CC). Patients homozygous ( GG) for the SNP in TNFAIP3 showed a worse response (∆ PASI) to ustekinumab ( P = 0·031) than the reference group ( TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary ( PASI 75) analysis. Conclusions We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis. [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 Treatment goals have been developed to optimize daily clinical practice psoriasis care, but have not yet been studied in real life. Objectives To investigate to what extent treatment decisions made by dermatologists in daily clinical practice for patients with psoriasis on biologics are already in accordance with treatment goals without the active application of the treatment goals algorithm. Methods Data were extracted from a prospective daily practice cohort of patients with psoriasis on biologics. Analysis was done on effectiveness (Psoriasis Area and Severity Index score) and quality of life (Dermatology Life Quality Index questionnaire). Treatment decisions such as dosage adjustments, combination treatments, or switching therapy were compared with the treatment goals algorithm. Results In 64% (253 of 395) of visits, physicians followed the treatment goals algorithm. There were 162 (41%) visits in which there should have been a treatment modification according to treatment goals (group Modify) and a modification was indeed made in 59 of these 162 visits (36%). In 233 (59%) visits no treatment modification was necessary (group Continue) and therapy was indeed not modified in 194 of 233 visits (83%). Conclusions Physicians acted in accordance with treatment goals in the majority of patient visits. In the patient group not achieving these goals, physicians should have modified therapy according to treatment goals but continued the same therapeutic regimen in the majority of visits. Optimizing therapy and defining barriers in the latter group might increase treatment results in daily practice psoriasis care. [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]

Background Long-term data of etanercept drug survival in patients with psoriasis in daily practice are scarce. Objectives The primary objective was to describe drug survival for etanercept in a long-term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy. Methods Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection. Results We included 193 patients (512 patient-years treated) with a maximum treatment duration of 7·5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7·5 years, respectively. The mean survival duration was 3·8 years (95% confidence interval 3·4-4·3). Reasons for discontinuation were ineffectiveness (33·7%), adverse events (11·9%), both ineffectiveness and adverse events (4·7%) or other reasons (e.g. pregnancy planned) (5·7%). Determinants related to longer general drug survival were male sex [hazard ratio ( HR) 0·55], prior anti-tumour necrosis factor ( TNF)-α use ( HR 0·57) and lower etanercept dose ( HR 0·65). Younger age ( HR 0·83), lower body mass index ( HR 0·63) and lower etanercept dose ( HR 0·71) were related to a decreased risk of discontinuation due to side-effects. A lower mean weekly dose of etanercept ( HR 0·63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy. Conclusions We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti- TNF therapy and lower etanercept dose. The determinants of longer drug survival depended on the reason for discontinuation of etanercept. [ABSTRACT FROM AUTHOR]

Background Auto-immune inflammatory rheumatic diseases (AIRD) are often successfully treated with the immunosuppressant azathioprine for years. Treatment with azathioprine has been proven to increase the risk of non-melanoma skin cancer (NMSC) in transplant patients and possibly in patients with inflammatory bowel disease as well. Little is known about the risk of NMSC in AIRD patients treated with azathioprine. Objectives The aim of this study is to determine the incidence of NMSC in patients with AIRD treated with azathioprine for at least 1 year, as compared with the general Dutch population. Methods Data were extracted from a historical cohort of patients with AIRD in a tertiary care centre. We compared the incidence to an age-matched control population and analysed risk factors for NMSC with univariate logistic regression. Results Fifty-nine patients were analysed. No patients were diagnosed with basal cell carcinoma and four patients with a single squamous cell carcinoma (SCC). Patients with SCC had a higher cumulative dose of azathioprine (≥500 g: OR 30.0 [95% CI 2.6-345.1]) and longer treatment duration (≥11 years: OR 13.5 [95% CI 1.3-143.6]). The risk of SCC compared with the general Dutch population was increased (standardized incidence ratio of 16.0 [95% CI 0.3-31.7]). Conclusions In this cohort of patients with AIRD treated with azathioprine for at least 1 year, the risk of SCC was increased, as compared with the general population. An individual cumulative dose of at least 500 g azathioprine and a treatment duration of at least 11 years were quantified as risk factors. [ABSTRACT FROM AUTHOR]

The article discusses research on the correlation between the clinical efficacy of ustekinumab, trough levels, and antidrug antibody (ADA) formations in patients with psoriasis. Topics covered include the comparison of the antigen-binding test with the enzyme-linked immunosorbent assay (ELISA), methodology of the study, and the factors affecting ustekinumab trough levels. Detection of antibodies to ustekinumab is also mentioned.

Linked Article: Mourad et al. Br J Dermatol 2019; 181:450–458. [ABSTRACT FROM AUTHOR]

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 The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. Objectives To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. Methods Data were extracted from the prospective, multicentre Bio CAPTURE registry. Multilevel linear regression analyses ( MLRAs) and generalized estimating equation ( GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index ( PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. Results We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment ( P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). Conclusions Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses drug survival for azathioprine and enteric-coated mycophenolate sodium in a long-term daily practice cohort of adult patients with atopic dermatitis.

Background Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis ( AD) are lacking. Objectives To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. Methods Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection. Results In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6 years, respectively. Reasons for discontinuation were controlled AD (26·4%), side-effects (22·2%), ineffectiveness (16·3%), side-effects plus ineffectiveness (6·2%) or other reasons (11·0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio ( HR) 0·91]. Older age was also associated with a decreased drug survival related to side-effects ( HR 1·14). An intermediate-to-high starting dose (> 3·5-5·0 mg kg−1 daily) was associated with an increased drug survival related to ineffectiveness ( HR 0·63). Conclusions This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness. [ABSTRACT FROM AUTHOR]

Background Concerns exist about a risk of non-melanoma skin cancer ( NMSC) in psoriasis patients and rheumatoid arthritis ( RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF-inhibitor therapy. Objective To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF-inhibitors. Methods Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF-inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti- TNF and other systemic therapies). Results The NMSC risk was significantly higher in the psoriasis group [fully adjusted HR 6.0 (1.6-22.4 95% CI)] with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2-13.4 95% CI) higher rate of NMSC. Conclusion The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease-related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF-inhibitors. [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]

A letter to the editor is presented on treatment of chronic hand eczema patients using methotrexate.