Dataset Information

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis.

ABSTRACT:

Introduction

Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments.

Methods

Online databases were searched for RCTs published through October 2021. Eligible studies were head-to-head comparisons between systemic therapies and/or placebo reporting 50%, 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) from baseline in adults with moderate to severe plaque psoriasis. Comparisons included tumor necrosis factor inhibitors, interleukin (IL)-17, IL-23, and IL 12/23 inhibitors, and systemic nonbiologics. A multinomial Bayesian NMA was used to derive estimates of the relative efficacy of deucravacitinib and other systemic therapies. Response probabilities for each treatment and corresponding 95% credible intervals (CrIs) for achieving a PASI response were calculated over short-, mid-, and long-term follow-up (weeks 10-16, 24-28, and 44-60).

Results

The NMA included 47 RCTs. Deucravacitinib showed the highest PASI 75 response rates among nonbiologic systemic therapies across time points. Deucravacitinib PASI 75 response rate (95% CrI) over short-term follow-up was 54.1% (46.5-61.6), within the range of first-generation biologics (etanercept, 39.7% [31.6-48.3]; infliximab, 79.0% [74.0-83.5]). At mid-term follow-up, deucravacitinib PASI 75 increased to 63.3% (58.0-68.4). At long-term follow-up, deucravacitinib PASI 75 was 65.9% (58.0-73.4), comparable to first-generation biologics adalimumab (62.8%; 55.3-69.6) and ustekinumab (68.0%; 64.6-71.5).

Conclusions

Patients receiving deucravacitinib were more likely to achieve PASI 75 response versus apremilast and methotrexate across all time points. The long-term PASI 75 response rate for deucravacitinib was similar to those of adalimumab and ustekinumab. The approval of deucravacitinib offers patients the choice of an oral therapy with long-term efficacy similar to that of some biologics.

SUBMITTER: Armstrong AW

PROVIDER: S-EPMC10613195 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis.

Armstrong April W AW Warren Richard B RB Zhong Yichen Y Zhuo Joe J Cichewicz Allie A Kadambi Ananth A Junqueira Daniela D Westley Tracy T Kisa Renata R Daamen Carolin C Augustin Matthias M

Dermatology and therapy 20231006 11

<h4>Introduction</h4>Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments.<h4>Methods</h4>Online databases were searched for RCTs published through October 2021. Eligible studies ...[more]

PMID: 37801281

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Project description:IntroductionDeucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, is approved in the United States to treat adults with moderate-to-severe plaque psoriasis (PsO). This study compared the long-term efficacy of deucravacitinib and adalimumab using results from long-term extension (LTE) trials.MethodsOpen-label LTE trials were identified for an indirect treatment comparison (deucravacitinib: POETYK PSO-LTE [NCT04036435]; adalimumab: REVEAL extension [NCT00195676]). To ensure study design comparability, patients initially randomized to placebo and switched to deucravacitinib or adalimumab after week 16 were compared. The primary outcome was an ≥ 75% reduction in Psoriasis Area and Severity Index score (PASI 75) at week 112 postrandomization. Secondary outcomes were PASI 75 at week 52 and an ≥ 90% reduction in PASI score (PASI 90) at weeks 52 and 112. Missing PASI data were imputed. A matching-adjusted indirect comparison was conducted; individual patient-level data from POETYK PSO-LTE were reweighted to balance baseline characteristics with those from the REVEAL extension.ResultsBefore reweighting, on average, patients in the POETYK PSO-LTE (N = 329) versus the REVEAL (N = 345) extension were older, had a lower body weight, received more prior systemic treatments, and had higher baseline PASI scores and week 16 placebo PASI 75 and PASI 90 response rates. Following reweighting, adjusted week 112 PASI 75 response rates were significantly higher for deucravacitinib versus adalimumab (67.2% vs. 54.0%; mean difference [95% CI], 13.2 [4.0-22.5] percentage points). Deucravacitinib had a numerically higher adjusted week 112 PASI 90 response rate (41.3% vs. 34.0%; mean difference [95% CI], 7.3 [-2.0 to 16.7] percentage points). The treatments had similar week 52 adjusted PASI 75 and PASI 90 response rates.ConclusionIn this interim analysis, adults with moderate to severe PsO had higher long-term response rates at 2 years when treated with deucravacitinib versus adalimumab. Deucravacitinib response rates remained stable whereas adalimumab response rates declined in year 2.

Project description:IntroductionBiologic treatments have made complete skin clearance in moderate to severe plaque psoriasis a real possibility. Although clinical trials demonstrated the superiority of bimekizumab over secukinumab, adalimumab, and ustekinumab, direct comparisons with other biologics are not available. This systematic literature review (SLR) and network meta-analysis (NMA) aimed to evaluate the 1-year efficacy and safety of bimekizumab versus other biologic systemic therapies for moderate to severe plaque psoriasis.MethodsWe conducted an SLR to retrieve published randomised controlled trials (RCTs) in patients with moderate to severe plaque psoriasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and PsycINFO on 13 January 2022. Two NMA types were used to analyse the long-term achievement of 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100): (1) NMA of cumulative clinical benefits, based on the area under the curve, from week 0 to 52; (2) multinomial NMA at weeks 44‒60. Binomial NMA was used to evaluate long-term serious adverse events (SAEs).ResultsThe SLR identified 38 RCTs, of which 19 were included in the NMA. Bimekizumab 320 mg administered every 4 weeks to week 16 then every 8 weeks (Q4W/Q8W) showed a greater cumulative average number of days of PASI 100 response compared with all other biologics. These differences were statistically significant versus all biologics, except risankizumab 150 mg. The multinomial NMA demonstrated that interleukin (IL)-17 and IL-23 inhibitors were the most efficacious treatments. No significant differences were found in long-term occurrence of SAEs.ConclusionBimekizumab 320 mg Q4W/Q8W was superior to most other treatments in maintaining complete skin clearance during the first year of treatment. It demonstrated a greater cumulative average number of days with completely clear skin while displaying a comparable safety profile compared with all other biologics.

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.

Project description:IntroductionBiologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO.MethodsA systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials.ResultsEighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab.ConclusionThis analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics.

Project description:IntroductionPsoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options.ObjectiveWith the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis.MethodsA literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis.ResultsOne placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97-18.48; χ2=4.08, I2=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12-16. No cardiovascular events, serious infections, or lab abnormalities were noted.ConclusionDeucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinib's superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

Project description: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.

Dataset Information

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis.

Introduction

Methods

Results

Conclusions

Publications

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis.

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