Latest Advances for the Treatment of Chronic Plaque Psoriasis with Biologics and Oral Small Molecules.
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ABSTRACT:
SUBMITTER: Bellinato F
PROVIDER: S-EPMC8258237 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.ObjectiveTo estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.Data sourcesA systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.Study selectionPhase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.Data extraction and synthesisData were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis.Main outcomes and measuresPASI 75, 90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline.ResultsSixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses.Conclusions and relevanceThis study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.
| S-EPMC7042876 | biostudies-literature
Project description:Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.
| S-EPMC2907770 | biostudies-literature
Project description:Real-world and long-term data on biologic treatment changes - including switching, discontinuation, dose escalation, and interval change (both increasing and decreasing) - are required to understand treatment patterns for psoriasis (PsO) in Canada. The study objectives were to evaluate the time to first biologic treatment change and to document these changes in Canadian patients with moderate-to-severe chronic plaque PsO. Charts from 13 Canadian sites were queried retrospectively (2005-2019); a period covering all biologic classes commonly used for PsO in Canada. Included were patients diagnosed with, and currently using biologics for, moderate-to-severe chronic plaque PsO. Time to first treatment change, nature of treatment change, number of lines of treatment, proportion of patients on each drug, and drug survival were collected. Based on 1149 medical charts, adalimumab had the longest time to first treatment change (49.3 months; 95% confidence interval, 37.4-67.4). Approximately half of the patients had a treatment change, and nearly 75% of these changes were either an interval change or a biologic switch. Lack of efficacy was the most prevalent primary reason for biologic switch (67.3%), whereas 6.7% of patients switched due to adverse events. Drug survival for etanercept and infliximab was approximately twice as long for patients who had dose optimization (i.e., dose escalation or interval change) than patients without dose optimization. The survival curve of adalimumab was similar to the one of ustekinumab after 48 months of treatment, showing approximately 60% of patients remaining on treatment after 132 months, with or without dose optimization. Assessing treatment patterns of all commonly used biologics for moderate-to-severe chronic plaque PsO in Canada between 2005 and 2019 showed that approximately half of the patients required a treatment change (mainly interval change or biologic switch) while the other half remained on treatment.
| S-EPMC9298415 | biostudies-literature
Project description:Background: The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Methods: Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). Results: A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What's more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. Conclusions: This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
| S-EPMC8281289 | biostudies-literature
Project description:Psoriasis is a relatively common, chronic and disabling skin disease, with an immune-related pathogenesis and a genetic background which may be triggered by several environmental factors including smoking and infections. There is no cure but several treatment options are available. The treatment of psoriasis is far from being satisfactory due to impractical modalities of topical treatment and suboptimal safety profile of the systemic treatments available. In the last few years, parallel to an improved understanding of the disease pathogenesis, there has been a boost in research on new agents for the treatment of psoriasis. Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is one such new agent. Psoriasis and its management are briefly reviewed before focusing on the evidence for ustekinumab in the treatment of chronic plaque psoriasis through a systematic search of the main registries of ongoing trials up to December 2009. Ustekinumab proved to be very effective short term in the control of clinical manifestations in psoriasis compared with placebo and with etanercept. Long-term and comparative data are still limited. There is a need for continuing research on the long-term effectiveness and safety of the drug.
| S-EPMC2880344 | biostudies-literature
Project description:IntroductionThe clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis.MethodsA systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration- or European Medicines Agency-licensed treatments for moderate-to-severe psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10-16 weeks from baseline) and maintenance periods (long-term: 48-52 weeks from baseline) were estimated using Bayesian network meta-analysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments.ResultsIn the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.9%, SUCRA 0.951), risankizumab (72.5%, 0.940), and brodalumab (72.0%, 0.930), which were significantly higher than those for guselkumab (65.0%, 0.795), secukinumab (65.0%, 0.794), infliximab (56.8%, 0.702), certolizumab (400 mg: 49.6%, 0.607; 200 mg: 42.2%, 0.389), ustekinumab (90 mg: 47.9%, 0.568; weight-based: 45.7%, 0.505; 45 mg: 44.6%, 0.460), adalimumab (43.0%, 0.410), tildrakizumab (200 mg: 39.7%, 0.327; 100 mg: 37.2%, 0.268), etanercept (18.0%, 0.171), apremilast (12.4%, 0.090), and dimethyl fumarate (12.2%, 0.092). The PASI 100 response rates were highest for ixekizumab (41.4%), risankizumab (40.8%), and brodalumab (40.3%). In the long term (N = 11 RCTs), the PASI 90 rate was highest for risankizumab (85.3%, SUCRA: 0.998), which were significantly higher than those for brodalumab (78.8%, 0.786), guselkumab (78.1%, 0.760), ixekizumab (72.1%, 0.577), secukinumab (67.0%, 0.450), ustekinumab (weight-based: 55.0%, 0.252), adalimumab (51.6%, 0.176), and etanercept (37.9%, 0.001). Risankizumab had the highest PASI 100 response rate (65.4%), followed by brodalumab (55.7%) and guselkumab (54.8%).ConclusionsIxekizumab, risankizumab, and brodalumab had the highest short-term efficacy, and risankizumab had the highest long-term efficacy.
| S-EPMC8163943 | biostudies-literature
Project description:Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.
| S-EPMC8470543 | biostudies-literature
Project description:Longitudinal nonlinear mixed effects modeling was used to characterize the dose–response profile of tofacitinib using data from a placebo-controlled dose-ranging study, where tofacitinib 2, 5, and 15 mg twice daily (b.i.d.) were evaluated for plaque psoriasis treatment. Bayesian estimation was applied with prior information derived from the literature: nonclinical and clinical data in psoriasis, as well as other indications. The probability to achieve a certain target effect associated with a given dose was calculated from the posterior samples. On the basis of these probabilities along with safety considerations, tofacitinib 5 and 10 mg b.i.d. were selected for further testing in confirmatory phase III clinical trials. Pharmacokinetics in patients with psoriasis was characterized using a population-based modeling approach, and body weight was identified as an important covariate. A subgroup analysis suggested reduced efficacy of tofacitinib with increasing body weight; however, it is unclear whether this trend could be explained by systemic exposure alone.
| S-EPMC3674331 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.
| S-EPMC8352818 | biostudies-literature
Project description:INTRODUCTION:Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. AIM:To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. MATERIAL AND METHODS:The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. RESULTS:The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. CONCLUSIONS:It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis.
| S-EPMC4436238 | biostudies-literature