Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors.Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations.Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning.Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Serum drug levels and anti-drug antibodies in the context of dose tapering by interval prolongation of adalimumab, etanercept and ustekinumab in psoriasis patients: results of the CONDOR trial.

BACKGROUND: Biologics for psoriasis are registered in standard dosages. In patients with low disease activity, reduction of the dose by interval prolongation can prevent overtreatment, and lower risks and costs. However, fear for increased anti-drug antibody (ADA) formation due to interval prolongation of biologics is an important barrier. OBJECTIVE: To investigate the course of serum drug concentrations, ADA levels, and predictors for successful dose reduction of adalimumab, ustekinumab, and etanercept for psoriasis. METHODS: Patients were randomized to dose reduction (DR) or usual care (UC) and followed for one year. The course and extent of detectable ADA levels were expressed as proportions/relative risks for DR vs. UC. Association of baseline characteristics with successful tapering was investigated with log-binomial regression analysis. RESULTS: In total, 118 patients were included. In adalimumab-treated patients, no significant difference in the proportion of patients with relevant ADA levels in DR vs. UC was seen. For ustekinumab, relevant ADA development was absent in both groups. Baseline trough levels were not predictive for successful DR. CONCLUSIONS: Immunogenicity may not increase by interval prolongation in psoriasis patients with low disease activity. This pilot provides important and reassuring insight into the pharmacological changes after dose tapering of adalimumab, etanercept, and ustekinumab.

Comparison of Tightly Controlled Dose Reduction of Biologics With Usual Care for Patients With Psoriasis: A Randomized Clinical Trial.

Importance: Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible. Objective: To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC). Design, Setting, and Participants: This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied. Interventions: Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose. Main Outcomes and Measures: The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for ≥3 months), and proportion of patients with successful dose tapering. Results: Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred. Conclusions and Relevance: In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues. Trial Registration: ClinicalTrials.gov Identifier: NCT02602925.

Good clinical response to anti-psoriatic treatment with adalimumab and methotrexate does not inflict a direct effect on compartmentalization of T-cell subsets: a pilot study.

OBJECTIVES: The most recently introduced therapeutics for psoriasis are biologicals which can target the T-cell-mediated pathology of psoriasis in a direct or indirect manner. The present pilot study focuses on and compares the effect of a conventional systemic agent (methotrexate; MTX) with the effect of a TNF-binding biological (adalimumab) on psoriasis-associated T-cell subsets in peripheral blood (PB) and lesional skin. Insight is provided in the hypothesized compartmentalization of these T-cell subsets between PB and the cutaneous compartment. METHODS: Immunohistochemical stainings of designated T-cell subsets on psoriatic skin sections were performed and similar subsets were isolated from PB specimens by flow cytometry. These counts were correlated with clinical severity. RESULTS: Results showed that adalimumab had a greater clinical effect than MTX treatment after 12 weeks. In the dermis, only the CD3+ T cells were significantly reduced after 12 weeks of adalimumab therapy, whereas for MTX only CD3+ T cells in the epidermis and CD45RO+ T cells in the dermis reduced significantly. However, PB T-lymphocyte populations did not show significant shifts in quantification of T-cell subsets. CONCLUSION: Therefore, recompartmentalization of psoriasis-associated T-cell subsets between PB and lesional skin was not induced in this study as a therapeutic principle. Consequently, recompartmentalization of T-cell subsets does not seem an obligatory event in order to achieve good clinical response.

Etanercept and efalizumab treatment for high-need psoriasis. Effects and side effects in a prospective cohort study in outpatient clinical practice.

BACKGROUND: Since the beginning of 2005, etanercept and efalizumab are officially registered and reimbursed for the treatment of recalcitrant psoriasis in The Netherlands. OBJECTIVE: The evaluation of the efficacy, safety and adverse events of etanercept and efalizumab treatment in daily practice. METHODS: A prospective cohort study was carried out for patients treated with etanercept or efalizumab between February 2005 and March 2006. RESULTS: Over the past 13 months 45 individuals were treated with etanercept and 17 subjects were treated with efalizumab. The cohort represented a high-need population. At week 12, 82% of the subjects treated with 2 x 50 mg etanercept/week and 71% of the subjects treated with 2 x 25 mg etanercept/week reached a PASI-50. Efficacy of etanercept treatment was comparable to the results of clinical trials. For efalizumab, efficacy in responding patients was also comparable to clinical trial data, but the percentage of dropouts was substantial. During biologic treatment, safety was preserved and mainly mild adverse events were reported. CONCLUSION: Etanercept and efalizumab are effective and safe treatments of psoriasis, even in a high-need population. Etanercept was able to sustain the clinical improvement throughout 24 weeks, whereas efalizumab was not in 47% of subjects.

Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and Fibroscan predicts the absence of significant liver fibrosis.

BACKGROUND: Methotrexate (MTX) use is associated with hepatic fibrosis in psoriasis patients. To monitor this serial liver biopsies were performed. The Fibroscan and the Fibrotest are two novel, non-invasive methods that might be able to assess MTX-induced hepatic fibrosis. AIM: Evaluating the accuracy and feasibility of the Fibroscan and Fibrotest to detect significant MTX-induced liver fibrosis in psoriasis patients. METHODS: We assessed 24 psoriasis patients who had a recent liver biopsy during MTX use. The results from the Fibroscan and Fibrotest were compared with liver histology. RESULTS: Fibroscan values (n=20) ranged between 3.3 and 18.4 kPa (median value 6.4 kPa) and correctly identified 88% of the patients without significant liver fibrosis (Metavir score /=F2, Fibrotest >0.31). CONCLUSION: In this population, Fibrotest accurately predicted the presence of significant liver fibrosis while the Fibroscan accurately predicted the absence of significant liver fibrosis in MTX users. This suggests that a combination of Fibrotest and Fibroscan should prospectively be evaluated in monitoring and detecting significant MTX-induced liver fibrosis in psoriasis patients.

Reliability of the Roenigk classification of liver damage after methotrexate treatment for psoriasis: a clinicopathologic study of 160 liver biopsy specimens.

OBJECTIVE: To determine the interobserver reliability of the Roenigk score as a classification system of liver damage and its possible consequences for clinical practice. DESIGN: Retrospective study. SETTING: Academic research. Patients One hundred sixty liver biopsy specimens from patients with psoriasis receiving methotrexate treatment were rereviewed and analyzed blindly by an experienced pathologist with an interest in liver pathologic conditions. Main Outcome Measure Interobserver variation was evaluated using kappa statistics. RESULTS: A high concordance was present in the evaluation of the Roenigk grade of fibrosis (weighted kappa = 0.73; 95% confidence interval, 0.63-0.83). Agreement was good regarding the number of biopsy specimens for patients whose clinical management should be changed (kappa = 0.71; 95% confidence interval, 0.56-0.87). Conclusion The Roenigk classification in the assessment of liver fibrosis is a reliable scoring system.