Dose Tapering of Biologics in Patients with Psoriasis: A Scoping Review.
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ABSTRACT: Introduction
Biologics serve as a cornerstone in psoriasis treatment, with low disease activity or sometimes even clinical remission as a realistic treatment outcome. So far, it is unclear whether biologics should be tapered when this target is achieved. Dose tapering could offer potential benefits by decreasing side effects, the burden of repetitive injections and costs of biological therapy. However, clinical guidelines on dose tapering of biologicals in psoriasis patients are lacking. This scoping review was conducted to provide an overview of the current literature on dose tapering and offer guidance for clinicians in daily clinical practice.Methods
Dose tapering is defined as the administration of a lower dose per administration, or the prolongation of the regular dose interval, after initial treatment according to the standard dosing. Four electronic databases (PubMed, EMBASE, Cochrane, and Web of Science) were systematically searched for literature on tapering of biologics in adult patients with psoriasis from 1 January 2000.Results
We included 19 original articles on biologic tapering in psoriasis patients: four randomized controlled trials and 15 observational studies. Tapering eligibility criteria, tapering strategies, tapering outcomes, and recapture of response after relapse were assessed. Furthermore, the available evidence on possible predictors for successful tapering, and the effect of tapering on safety, quality of life and costs is summarized. The definition of low disease activity as a measure for tapering eligibility varied widely. Beside tapering criteria, tapering strategies were also heterogeneous. Of note, quality-of-life measurements were barely integrated in the evaluation of tapering outcomes. Literature on regaining response after relapse due to tapering was limited, but restored remission has been described. The included studies did not proclaim a significant effect of tapering on the occurrence of (severe) adverse events. Even though cost savings have been reported, no proper cost-effectiveness analysis has been conducted yet.Conclusion
Biologic tapering seems to be effective and safe in psoriasis patients with stable low disease activity or clinical remission. Available data on biologic dose tapering in patients with psoriasis are promising, but more research is warranted to fill the current gaps in knowledge.
SUBMITTER: Michielsens CAJ
PROVIDER: S-EPMC7952351 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceBiologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible.ObjectiveTo investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC).Design, setting, and participantsThis 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.InterventionsPatients 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 measuresThe 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.ResultsOf 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 relevanceIn 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 registrationClinicalTrials.gov Identifier: NCT02602925.
| S-EPMC7042801 | biostudies-literature
Project description:ImportanceBiologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.ObjectiveTo explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.Design, setting, and participantsThis prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.ExposuresDuration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.Main outcomes and measuresIncidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models.ResultsOf 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).Conclusions and relevanceIn this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.
| S-EPMC10701661 | biostudies-literature
Project description: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.
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Project description:BackgroundPatients with psoriasis may experience an exacerbation in symptoms following COVID-19 infection. After abandoning 'zero COVID' strategies, China experienced a surge of Omicron infections.ObjectivesWe aimed to investigate psoriasis exacerbation in psoriatic patients with COVID-19, following treatment with three different biologics, adalimumab, secukinumab, and ixekizumab.MethodsWe performed a prospective study (n = 209) at our hospital between November 01, 2022, and February 15, 2023. We defined △ PASI as post-COVID-19 PASI minus pre-COVID-19 PASI. Two endpoints were set in this study. △ PASI >0 was defined as exacerbation of psoriasis after infection. △ PASI >3 was defined as a severe exacerbation of psoriasis symptoms after infection. In addition, serum OAS1, OAS2, and OAS3 were also assessed.ResultsResults showed that the severity of psoriasis can worsen after COVID-19 infection, and a smaller proportion of patients taking biologics developed worsening psoriasis compared to those not using biologics; however, only the patients taking ixekizumab demonstrated a statistically significant difference (p < 0.05), while those taking adalimumab or secukinumab didn't. What's more, the use of biological agents suppressed the serum OAS2 and OAS3 at low levels and elevated the serum OAS1 level in patients with psoriasis.ConclusionsThis study provided new insights into the protective role of biological agents in patients with psoriasis who were infected with COVID-19, and we proposed that psoriatic patients treated with biologics should continue with the treatment during the COVID-19 pandemic.
| S-EPMC10828055 | biostudies-literature
Project description:IntroductionPsoriasis is a common chronic skin inflammatory disease. Its presentation, apart from affected skin areas, involves other unpleasant symptoms, such as pain. Pain deteriorates the patient's quality of life, impairing their daily behaviour and functioning. Therefore, the alleviation of pain in patients with psoriasis should be one of the most desired outcomes of successful treatment. The aim of this study is to summarise available evidence about pain in patients with psoriasis using systematic scoping review methodology in order to map the relevant literature.Methods and analysesOur scoping systematic review will provide evidence synthesis of the literature, both quantitative and qualitative, about the pain associated with psoriasis, including pain associated with psoriatic arthritis. Any types of studies will be eligible for inclusion, and we will not have any time, language or publication status restrictions. We will search MEDLINE, Embase and PsycINFO via OVID, as well as Cochrane Central Register of Clinical Trials, Cochrane Database of Systematic Reviews via Cochrane Library, CINAHL via EBSCO, OpenGrey and ProQuest Dissertations and Theses Global. All databases will be searched from the date of their inception. Retrieved bibliographic records and potentially relevant full texts will be screened by two authors independently. Two researchers will extract data independently. Any discrepancies will be resolved via discussion or consultation of the third author, if necessary. To appraise studies, we will use a Mixed Methods Appraisal Tool, AMSTAR 2, Cochrane risk of bias tool and ROBINS. Our findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews.Ethics and disseminationThe proposed study will not be conducted with human participants. We will only use published data and therefore ethics approval is not required. Our findings will be disseminated via peer-reviewed manuscript and conference reports.
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Project description:BackgroundProportion of days covered (PDC), a commonly used adherence metric, does not provide information about the longitudinal course of adherence to treatment over time. Group-based trajectory model (GBTM) is an alternative method that overcomes this limitation.MethodsThe statistical principles of GBTM and PDC were applied to assess adherence during a 12-month follow-up in psoriasis patients starting treatment with a biologic. The optimal GBTM model was determined on the basis of the balance between each model's Bayesian information criterion and the percentage of patients in the smallest group in each model. Variables potentially predictive of adherence were evaluated.ResultsIn all, 3,249 patients were included in the analysis. Four GBTM adherence groups were suggested by the optimal model, and patients were categorized as demonstrating continuously high adherence, high-then-low adherence, moderate-then-low adherence, or consistently moderate adherence during follow-up. For comparison, four PDC groups were constructed: PDC Group 4 (PDC ≥75%), PDC Group 3 (25%≤ PDC <50%), PDC Group 2 (PDC <25%), and PDC Group 1 (50%≤ PDC <75%). Our findings suggest that the majority of patients (97.9%) from PDC Group 2 demonstrated moderate-then-low adherence, whereas 96.4% of patients from PDC Group 4 showed continuously high adherence. The remaining PDC-based categorizations did not capture patients with uniform adherence behavior based on GBTM. In PDC Group 3, 25.3%, 17.2%, and 57.5% of patients exhibited GBTM-defined consistently moderate adherence, moderate-then-low adherence, or high-then-low adherence, respectively. In PDC Group 1, 70.8%, 23.6%, and 5.7% of patients had consistently moderate adherence, high-then-low adherence, and continuously high adherence, respectively. Additional analyses suggested GBTM-based categorization was best predicted by patient age, sex, certain comorbidities, and particular drug use.ConclusionGBTM is a more appropriate way to model dynamic behaviors and offers researchers an alternative to more traditional drug adherence measurements.
| S-EPMC3986333 | biostudies-literature
Project description:BackgroundLong-term use of oral corticosteroids (OCS) is associated with a risk of adverse events and comorbidities. As such, a goal in assessing the efficacy of biologics in severe asthma is often to monitor reduction in OCS usage. Importantly, however, OCS dose reductions must be conducted without loss of disease control.Main bodyHerein, we describe the development of OCS-sparing study methodologies for biologic therapies in patients with asthma. In particular, we focus on four randomized, placebo-controlled, parallel-group studies of varying sizes (key single-center study [n = 20], SIRIUS [n = 135], ZONDA [n = 220], VENTURE [n = 210]) and one open-label study (PONENTE [n = 598]), which assessed the effect of asthma biologics (mepolizumab, benralizumab or dupilumab) on OCS use using predefined OCS-tapering schedules. In particular, we discuss the evolution of study design elements in these studies, including patient eligibility criteria, the use of tailored OCS dose reduction schedules, monitoring of outcomes, the use of biomarkers and use of repetitive assessments of adrenal function during OCS tapering.ConclusionTaken together, these developments have improved OCS-sparing asthma studies in recent years and the lessons learned may help with optimization of further OCS-sparing studies, and potentially clinical practice in the future.
| S-EPMC8896284 | biostudies-literature
Project description:Nowadays, it is well established a link between psoriasis and cardiovascular (CV) diseases. A series of different overlapping mechanisms including inflammation, homeostasis dysregulation, and genetic susceptibility are thought to underlie this association. Advances in understanding the molecular patterns involved in the complex scenario of psoriasis have highlighted a tight correlation with atherosclerosis. Indeed, common profiles are shared in term of inflammatory cytokines and cell types. In the last decade, the management of psoriasis patients has been revolutionized with the introduction of biological therapies, such as tumor necrosis factor-alpha (TNF-?), interleukin (IL)-12/23, and IL-17 inhibitors. In clinical setting, the effectiveness of these therapies as well as the incidence of CV events is related to the type of biologics. In particular, anti-TNF-? agents seem to reduce these events in psoriasis patients whereas anti-IL-12/23 agents related CV events reduction still remain to clarify. It has to be taken into account that IL-12/23 inhibitors have a shorter post-marketing surveillance period. An even more restricted observational time is available for anti-IL-17 agents. IL-17 is associated with psoriasis, vascular disease, and inflammation. However, IL-17 role in atherosclerosis is still debated, exerting both pro-atherogenic and anti-atherogenic effects depending on the specific context. In this review, we will discuss the differences between the onset of CV events in psoriasis patients, referred to specific biological therapy and the underlying immunological mechanism. Given the development of new therapeutic strategies, the investigation of these inhibitors impact on heart failure outcome is extremely important.
| S-EPMC6099159 | biostudies-literature
Project description:BackgroundPatients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.MethodsA 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.ResultsFifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.ConclusionsGuided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.
| S-EPMC10594210 | biostudies-literature
Project description:BackgroundIdentification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.ObjectivesTo identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.MethodsA systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.ResultsOf 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.ConclusionsThis review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.
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