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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.

Background/objectives: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission., Methods: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed., Results: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC., Conclusions: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

The development of psoriasis is associated with the consequences of oxidative stress and inflammation leading to metabolic changes locally, in the skin cells, and systemically, in the blood. Therefore, the aim of this study was to analyze the effect of psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) on the basal plasma/keratinocyte levels of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), and angiogenesis factors, as well as to evaluate the effect of CBD on these parameters in keratinocytes isolated from psoriatic/healthy individuals with and without in vitro irradiation by UVB. A quantitative chemiluminescent method of detection based on an ELISA protocol and zymography technique was used during analysis. It was shown that activity levels of MMP-9 and TIMP-2 in PsA plasma were higher than in PsV. Changes in the proteolytic activity were accompanied by an increase in markers of angiogenesis (angiopoietin-2, HGF, VEGF, TNF α , PDGF, FGF), where in the specific case of angiopoietin-2 and TNF α , the overexpression in PsV was significantly stronger than in PsA. CBD application to keratinocytes partially restored levels of MMP-1/2/3/7 and TIMP-1/2 (in an effect which was particularly enhanced by UVB irradiation), as well as levels of the examined angiogenic factors except TNF α (levels of which were increased in psoriatic keratinocytes and decreased in healthy keratinocytes). Presented results indicate that CBD may be suggested as an antiangiogenic factor that reduces the proinflammatory action of UVB in psoriatic keratinocytes and partially has a protective effect for healthy keratinocytes., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Agnieszka Gęgotek et al.)

Dose reduction of biologics for psoriasis could contribute to lower drug exposure. This study evaluated a one-step, tightly controlled, biologic dose reduction strategy in a prospective daily practice cohort. In patients with psoriasis with low disease activity using adalimumab, etanercept or ustekinumab for at least 6 months, the dosing interval was prolonged with 33%. Patients could return to their normal dosing interval in case of disease flare. Of 108 eligible patients, 80 started dose reduction and were analysed. In total, 36/80 patients (45.0%) discontinued dose reduction after 19 months (95% confidence interval 14.9-23.1 months). Of 67 patients with 1-year follow-up, 45 (67.2%) still used the lower dose after 1 year. No serious adverse events related to dose reduction occurred. Cumulative dose and costs decreased by 22.7% during 1 year. In conclusion, a one-step tightly controlled dose reduction strategy for adalimumab, etanercept and ustekinumab has considerable potential to safely decrease biologic dosages in patients with psoriasis in daily practice.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

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.

Background: Psoriasis is an immune-mediated chronic inflammatory skin disorder for which several targeted biologic therapies became available in the last 10 years. Data from patients with rheumatoid arthritis revealed that dose tapering combined with tight control of disease activity is successful. For psoriasis patients the lowest effective dose of biologics needs to be determined. The objective was to assess whether dose tapering of biologics guided by Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI) scores in psoriasis patients with controlled disease activity is non-inferior (NI) to usual care., Methods/design: This is a multicenter, pragmatic, randomized, non-inferiority trial with cost- effectiveness analysis. One hundred and twenty patients with stable low disease activity (PASI ≤ 5 and DLQI ≤ 5) for at least 6 months with a stable use of adalimumab, etanercept or ustekinumab will be randomized 1:1 to the dose reduction group or usual care. In the dose reduction group, the treatment intervals will be prolonged stepwise, resulting in a 33% and 50% dose reduction, respectively. Disease activity is monitored every three months with PASI and DLQI. In case of flare the treatment is adjusted to the previous effective dose. The primary outcome (PASI) at 12 months will be analyzed with ANCOVA in which the baseline PASI will be included as covariate to gain efficiency. The secondary outcomes include number of and time to disease flares, health-related quality of life, serious adverse events, and costs., Discussion: With this study we want to assess whether disease activity guided dose reduction of biologics can be achieved for psoriasis patients with low stable disease activity, without losing disease control. By using the lowest effective dose of biologics, we expect to minimize side effects and save costs., Trial Registration: This trial was registered at ClinicalTrials.gov ( NCT 02602925 ). Trial registration date October 9 2015.

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., (© 2016 British Association of Dermatologists.)

Background: Personal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease. Objectives: To explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab. Methods: Treatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥ 6 months and preferably a Psoriasis Area and Severity Index (PASI) < 5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (< 50 vs. ≥ 50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy. Results: Sixty-five patients were included. 'To be free of itching', 'to be healed of all skin defects' and 'to have confidence in the therapy' were rated quite/very important in 78.5% of the patients, followed by 'to have no fear the disease will progress' (75.4%) and 'to get better skin quickly' (75.4%). Goals related to the subscale 'confidence in healing' were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to 'feel less depressed' and 'be comfortable showing yourself more in public'. Conclusions: Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level. Plain Language Summary: In psoriasis patients, a large reduction in disease severity can lead to a significant improvement in health-related quality of life. In addition to quality-of-life measurements, individual treatment goals can be assessed to evaluate patients' preferences regarding their psoriasis treatment. As opposed to patients with more severe psoriasis, unmet treatment needs in psoriasis patients with stable, low disease activity have barely been reported. In this study, the personal treatment aims of patients with controlled disease due to treatment with adalimumab, etanercept or ustekinumab were explored using the Patient Needs Questionnaire. Sixty-five patients with sustained low disease activity for ≥ 6 months were included. We found that despite low disease activity, these patients still have substantial patient needs. Patients attributed the highest importance to goals on confidence in healing, in contrast to social goals, which were valued of least importance. For female patients, it was significantly more important to 'feel less depressed' and 'be comfortable showing yourself more in public' compared to male patients. Previous treatment with biologic therapy was not associated with an altered attitude towards specific treatment goals. Our population with low disease activity seemed to award a lower level of importance to all treatment goals compared to groups of patients with more severe psoriasis that have been described in literature. Since treatment goals differ per patient, individual treatment could be optimized by actively inquiring about the patient's personal treatment goals. Clinicians should be aware that even in patients with controlled disease, substantial personal treatment needs remain. [ABSTRACT FROM AUTHOR]