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Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75-100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0-2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one "on-demand" dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice., Competing Interests: MvM carried out clinical trials for AbbVie, Celgene, Janssen, and Novartis and received a speaking fee from Janssen. All funding is not personal but goes to the independent Research Fund of the Department of Dermatology of the Radboud University Medical Centre, Nijmegen (Radboudumc), Netherlands. LvS carried out clinical trials for Almirall, Janssen, and Novartis. All funding is not personal but goes to the independent Research Fund of the Department of Dermatology of the Radboud University Medical Centre, Nijmegen, Netherlands. JvR carried out clinical trials for AbbVie, Celgene, and Janssen and received speaking fees/attended advisory boards from AbbVie, Janssen, BMS, Almirall, Leo Pharma, Novartis, UCB, and Eli Lilly and reimbursement for attending a symposium from Janssen, Pfizer, Celgene, and AbbVie. All funding is not personal but goes to the independent research fund of the Department of Dermatology of Radboudumc, Nijmegen, Netherlands. EJ received research grants from the independent research fund of the Department of Dermatology of Radboudumc, Nijmegen, Netherlands, from AbbVie, BMS, Janssen, Leo Pharma, Novartis, and UCB for research on psoriasis and acted as a consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis or eczema, including AbbVie, Amgen, Almirall, Celgene, Galapagos, Janssen, Eli Lilly, Novartis, Leo Pharma, Sanofi, and UCB. All funding is not personal but goes to the independent research fund of the Department of Dermatology of Radboudumc, Nijmegen, Netherlands., (Copyright © 2024 van Riel, Michielsens, van Muijen, van der Schoot, van den Reek and de Jong.)

Background: 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., Objectives: To evaluate the implementation of protocolized biologic DR in daily practice., Methods: 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., Results: 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., Conclusion: 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.

Dose reduction of biologics for psoriasis could contribute to more efficient use of these expensive medicines. Evidence on opinions of patients with psoriasis regarding dose reduction is sparse. The objective of this study was therefore to explore patients' perspectives towards dose reduction of biologics for psoriasis. A qualitative study was conducted, comprising semi-structured interviews with 15 patients with psoriasis with different characteristics and treatment experiences. Interviews were analyzed by inductive thematic analysis. Perceived benefits of biologic dose reduction according to patients were minimizing medication use, lowering risks of adverse effects and lowering societal healthcare costs. Patients reported to have experienced a large impact of their psoriasis, and expressed concerns about loss of disease control due to dose reduction. Fast access to flare treatment and adequate monitoring of disease activity were among reported preconditions. According to patients, they should have confidence in dose reduction effects and should be willing to change their effective treatment. Moreover, addressing information needs and involvement in decision-making were deemed important among patients. In conclusion, addressing patients' concerns, fulfilling information needs, providing the possibility of resuming standard dose, and involving patients in decision-making are important according to patients with psoriasis when considering biologic dose reduction., (© 2023. The Author(s).)

Background: Dose reduction of biologics for psoriasis is applied in daily practice, although guidelines are lacking. Striving for clear criteria is important, as it leads to a consistent application of dose reduction., Objective: To achieve consensus on criteria for biologic dose reduction in psoriasis patients with stable and low disease activity., Methods: An online Delphi procedure (eDelphi) was conducted. Dutch dermatologists were invited to participate in a maximum of 3 voting rounds. Proposed statements were selected based on literature review and included criteria for the application of dose reduction and dosing schedules. Biologic dose reduction was defined as 'application of injection interval prolongation'. Proposed statements were rated using a 9-point Likert scale; consensus was reached when ≥70% of all voters rated 'agree' (7-9) and <15% rated 'disagree' (1-3)., Results: A total of 27 dermatologists participated and reached a consensus on 15 recommendations over 2 voting rounds. Agreed statements included criteria for dose reduction eligibility, criteria for dose reduction (dis)continuation, and dosing schedules for adalimumab, etanercept, and ustekinumab. Based on the eDelphi outcomes, an algorithm fit for implementation in current practice was developed., Conclusions: Recommendations of this national consensus process can guide clinicians, and consequently their patients, toward consistent application of biologic dose reduction.

Dose reduction (DR) of biologics, where possible, seems promising for more efficient use of expensive biologics. For implementation of DR strategies, it is essential to get insight in factors that influence implementation. The objective of this study was to evaluate the attitudes and behaviour regarding dose reduction of biologic therapies for psoriasis among psoriasis expert dermatologists worldwide. A 27-question e-survey was sent through the International Psoriasis Council (IPC) to its 114 dermatologist councilors worldwide. The survey assessed demographics, general and DR prescription behaviour, and motivations for and barriers against application of DR. Of 57 respondents, 53 respondents who prescribed biologics were included for analysis. Thirty-seven (69.8%) applied DR (i.e., 'DR dermatologists'), and 16 (30.2%) did not (i.e., 'Non-DR dermatologists'). DR strategies varied among respondents. Regarding criteria for starting DR, differences were reported in required treatment duration, and interpretation and duration of stable low disease activity. In addition, the prolongation of intervals between injections varied between respondents. For most 'DR dermatologists' (n = 32/37, 86.5%), cost savings were one of the main reasons to apply DR. Fifteen out of 16 'Non-DR dermatologists' (94%) did not apply DR due to lack of scientific evidence. In conclusion, DR of biologics for psoriasis is part of clinical practice in psoriasis experts globally. Barriers for applying DR included lack of evidence or guidelines, and uncertainty on DR effects and risks. Although growing evidence shows DR feasibility, future studies are needed to accumulate and broaden evidence, along with development of (inter)national guidelines on DR strategies., (© 2021. The Author(s).)

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC)., Methods: This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC., Discussion: With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics., Trial Registration: ClinicalTrials.gov NCT04340076 . Registered on April 9 2020., (© 2021. The Author(s).)

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.

Importance: Treating older adults with psoriasis can be challenging owing to comorbidities, concomitant medication use, and consequent safety risks. Although many studies focus on the effectiveness and safety of systemic antipsoriatic therapies in the general population, their effectiveness in older adults with psoriasis has not been systematically assessed., Objective: To evaluate the effectiveness and safety of systemic antipsoriatic therapies in patients 65 years or older., Evidence Review: A systematic literature search was conducted in Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 11, 2019. No date limit was used. Randomized clinical trials, cohort studies, large case series, and meta-analyses assessing efficacy (or effectiveness) and/or safety of systemic antipsoriatic therapies in patients 65 years or older were included., Findings: The initial search yielded 11 096 results, of which 31 unique articles with 39 561 patients were included in analysis. Overall, limited data were available per systemic agent, and overall quality of the included studies on conventional systemic therapies was low. At the end of the induction phase (12-16 weeks after start of treatment), a reduction of 75% in Psoriasis Area and Severity Index was achieved in 49% of 74 methotrexate sodium users 65 years or older, 46% to 52.6% of 178 older cyclosporin users, 27% to 47.8% of 108 older acitretin users, 15.6% to 64% of 256 etanercept users 65 years or older, 66.7% to 93% of 43 infliximab users 65 years or older, 60.7% to 65% of 100 adalimumab users 65 years or older, 56.5% of 46 ustekinumab users 65 years or older, and 86.4% of 67 secukinumab users 65 years or older. Effectiveness of acitretin, etanercept, adalimumab, and secukinumab appeared not to be associated with age; studies regarding other systemic antipsoriatic therapies did not provide age group comparisons. Older age was significantly associated with renal function deterioration in cyclosporin users and with lymphopenia in fumaric acid esters users (hazard ratio, 2.42; 95% CI, 1.65-3.55; P < .001). Infections were the most frequently reported adverse event in patients 65 years or older using biologics, but no significant association with age was found., Conclusions and Relevance: On the basis of limited available evidence, age alone should not be a limiting factor in psoriasis management. Awareness of comorbidities and concomitant medication use is very important, as well as appropriate dosing and frequent laboratory and clinical monitoring. More real-world evidence and (sub)analyses of prospective cohort studies on the effectiveness and safety of systemic therapies in older adults are critical to optimize personalized, effective, and safe antipsoriatic management in this growing patient group.

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., (© 2019 European Academy of Dermatology and Venereology.)