A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis.
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ABSTRACT:
SUBMITTER: Campa M
PROVIDER: S-EPMC4799039 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionMany targeted, systemic therapies have been developed for treatment of moderate-to-severe psoriasis (PsO). A network meta-analysis (NMA) allows for comparison between treatments not directly compared in randomized controlled trials (RCT). This study's objective was to compare the short-term (10-16 weeks) clinical efficacy according to the Psoriasis Area and Severity Index (PASI) among approved biologic treatments for moderate-to-severe PsO using a novel (enhanced) NMA model.MethodsA systematic literature review (SLR) of RCTs for patients with moderate-to-severe PsO was conducted. English publications in MEDLINE, Embase, and The Cochrane Library up to March 2019 were searched. An enhanced multinomial Bayesian NMA was performed to simultaneously adjust for baseline risk and utilize the conditional nature of the PASI (50, 75, 90, and 100) levels. The model relaxes typical constraints that all treatments must have the same ranks across PASI levels.ResultsThe SLR resulted in 319 relevant publications, of which 72 publications from 73 RCTs reporting 10- to 16-week data for at least one PASI response level (30,314 total patients) were included. Interleukin (IL) inhibitors (risankizumab, ixekizumab, brodalumab, secukinumab, and guselkumab) were the best performing treatments for achieving all PASI levels. Etanercept was outperformed by the other subcutaneous tumor necrosis factor α inhibitors. Application of an enhanced NMA model that allowed treatment rankings to differ by PASI level tested the robustness of results of previous NMAs in PsO.ConclusionThe results of this model confirmed that IL inhibitors are likely the best short-term treatment choices for improving all PASI levels.
| S-EPMC8611163 | biostudies-literature
Project description:BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy.MethodsThe annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%).ResultsThe most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time.ConclusionBiologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.
| S-EPMC8422702 | biostudies-literature
Project description:BackgroundBiologics has been known to be effective for patients with psoriasis. However, optimal treatment pathways and their cost-effectiveness are limited in a resource-limited country. This study assessed the cost-effectiveness of different sequential biologics for moderate-to-severe plaque psoriasis.MethodA hybrid model from a societal perspective was used. Model inputs were derived from network meta-analysis, clinical trials, and published literature. Three different sequential biologic treatments were assessed; Sequence 1; 1st Interleukin-17 (IL-17) inhibitor (secukinumab) followed by 2nd IL-17 inhibitors (ixekizumab or brodalumab), then 3rd IL-23 inhibitor (guselkumab), Sequence 2; ixekizumab followed by secukinumab or brodalumab, then guselkumab, and Sequence 3; brodalumab followed by ixekizumab or secukinumab, then guselkumab. Methotrexate or ciclosporin was used as standard of care (SoC).ResultsAll three different sequential biologic therapies could gain total quality-adjusted life year (QALY), but they had higher cost than SoC. Sequence 1 had the lowest incremental cost-effectiveness ratio (ICER) compared to SoC at 621,373 THB/QALY (19,449 $/QALY). ICER for Sequence 2 was 957,258 THB/QALY (29,962 $/QALY), while that for Sequence 3 was 1,332,262 THB/QALY (41,700 $/QALY). Fully incremental analysis indicated that Sequence 3 was dominated by Sequence 1 and Sequence 2. ICER for Sequence 2 was 7,206,104 THB/QALY (225,551 $/QALY) when compared to Sequence 1.ConclusionAt the current willingness-to-pay of 160,000 THB/QALY, no sequential IL-17 inhibitor was cost-effective compared to SoC. Secukinumab followed by ixekizumab or brodalumab then guselkumab (Sequence 1) may be the most appropriate option compared with other treatments.
| S-EPMC11315331 | biostudies-literature
Project description:BackgroundThe role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis.ObjectiveTo compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA).MethodsA comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA).ResultsThis meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%).ConclusionsIL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.
| S-EPMC6754904 | biostudies-literature
Project description:IntroductionDose escalation and reduction of biologic treatments are frequent in clinical practice. The aim of this systematic review is to summarise evidence on dose adjustment of biologic treatments for moderate-to-severe plaque psoriasis in the real-world.MethodsA systematic review of real-world evidence on dose adjustment of biologics for plaque psoriasis was performed. Searches were conducted in BIOSIS Previews®, Embase®, International Pharmaceutical Abstracts, MEDLINE®, and SciSearch® in March 2020. Real-world studies that reported biologic dose adjustment for moderate-to-severe plaque psoriasis were included.ResultsThe search identified 162 papers, and 20 studies with 30,912 patients were included from 2014 to 2020. More studies reported on dose escalation than dose reduction. For adalimumab, 3-54% of patients had dose reduction while 0-37% had dose escalation. For infliximab, only two studies reported a dose reduction, with rates of 22-29%, while dose escalation rates varied from 14 to 67%. Dose reduction rates of 5-49% were reported for etanercept while 0-55% of patients had doses escalated. For ustekinumab, dose escalation and reduction rates ranged from 3 to 37% and 7 to 42%, respectively. Two studies reported on dose adjustment for secukinumab; in one 52% of patients initiated on 150 mg instead of the recommended 300 mg, while another reported no dose increase.ConclusionsDose adjustment of biologics for psoriasis is common, with escalation more frequently reported than reduction. Dose escalation may have economic and safety consequences, while dose reduction may impact efficacy. These aspects are important to consider when making decisions on treatment dosing.
| S-EPMC8322248 | biostudies-literature
Project description:Objectives: To asses skin clearance and patient-reported outcomes for ixekizumab treatment. Methods: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician’s Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. The trial was registered with ClinicalTrials.gov (NCT03573323).
2023-04-10 | GSE178228 | GEO
Project description:BackgroundRisankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials.ObjectivesTo evaluate safety data from risankizumab psoriasis phase I-III clinical trials.MethodsShort-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials.ResultsShort-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients.ConclusionsRisankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.
| S-EPMC9298814 | biostudies-literature
Project description:Risankizumab (Skyrizi®; risankizumab-rzaa) is a humanized immunoglobulin (Ig) G1 monoclonal antibody that specifically targets the p19 subunit of interleukin (IL)-23, thereby inhibiting IL-23-dependent cell signaling. Subcutaneous risankizumab is approved for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy (in the EU), those who are candidates for systemic therapy or phototherapy (in the USA) and those who have an inadequate response to conventional therapies (in Japan). In pivotal phase III trials (UltIMMa-1, UltIMMa-2, IMMvent and IMMhance), risankizumab was more effective than placebo, ustekinumab and adalimumab with regard to the proportion of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index score (PASI 90) and a static Physician's Global Assessment score of 0 or 1 at week 16, with these benefits maintained over the longer term. In supportive head-to-head trials, risankizumab was also superior to secukinumab and fumaric acid esters in terms of PASI 90 response rate. In an ongoing open-label extension study (LIMMitless), risankizumab was associated with durable and improved efficacy after switching from ustekinumab or adalimumab, as well as durable maintenance of efficacy through > 2.5 years of continuous exposure. Treatment with risankizumab improved health-related quality of life and was generally well tolerated, both in the short- and longer-term. In conclusion, risankizumab represents a useful new treatment option for patients with moderate to severe plaque psoriasis.
| S-EPMC7475056 | biostudies-literature
Project description:Background: Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood. Methods: IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4+ T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis. Results: IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients. Conclusion: Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.
| S-EPMC6693306 | biostudies-literature
Project description:Subcutaneous secukinumab (Cosentyx®) is a recombinant, fully human, immunoglobulin (Ig) G1κ monoclonal antibody targeted against interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriasis. Secukinumab is approved in the EU and the USA for the treatment of moderate to severe plaque psoriasis in pediatric patients aged ≥ 6 years. In pivotal phase III trials in pediatric patients aged 6 to < 18 years, both low (75-150 mg) and high (75-300 mg) doses of secukinumab were significantly better than placebo and numerically better than etanercept at week 12 in terms of the proportion of patients achieving ≥ 75% improvement from baseline in Psoriasis Area and Severity Index and significantly better than placebo and etanercept in terms of the proportion of patients achieving an Investigator's Global Assessment score of 0 or 1. The clinical efficacy of secukinumab observed during the first 12 weeks of treatment was maintained over the longer term. Treatment with secukinumab improved health-related quality of life and was generally well tolerated. In conclusion, secukinumab represents a valuable new addition to the limited treatment options available for children and adolescents with moderate to severe plaque psoriasis.
| S-EPMC8599386 | biostudies-literature