Dataset Information

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

ABSTRACT:

Background

Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed.

Objective

To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year.

Methods

An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention-to-treat approach with non-responder imputation were used.

Results

Twenty-four studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52-week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long-term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long-term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded.

Conclusion

Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long-term active-comparator RCT data are required to better assess relative efficacy across therapies.

SUBMITTER: Sawyer LM

PROVIDER: S-EPMC6587780 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

Sawyer L M LM Cornic L L Levin L Å LÅ Gibbons C C Møller A H AH Jemec G B GB

Journal of the European Academy of Dermatology and Venereology : JEADV 20181031 2

<h4>Background</h4>Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed.<h4>Objective</h4>To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and ...[more]

PMID: 30289198

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Project description:IntroductionThe long-term benefit-risk profiles of licensed and investigational treatments for moderate-to-severe plaque psoriasis have not been fully characterized.MethodsRandomized controlled trials (RCTs) of licensed and investigational treatments for moderate-to-severe plaque psoriasis were identified through a systematic literature review through 2 May 2021. Bayesian network meta-analyses (NMAs) were conducted to compare the efficacy (Psoriasis Area and Severity Index [PASI] 75/90/100 [at least a 75/90/100% reduction in PASI score from baseline] response) and safety outcomes (any adverse event [AE], any serious AE [SAE], and AEs leading to treatment discontinuation) of each treatment evaluated between weeks 48 and 56 after baseline. Surfaces under the cumulative ranking curves (SUCRAs) were calculated to evaluate the relative ranking of treatments. The benefit-risk profiles of treatments were assessed by bidimensional plots of the NMA-estimated efficacy and safety outcomes.ResultsIn the efficacy NMA (N = 14 RCTs), the relative rankings for PASI 75/90/100 responses by weeks 48-56 were the highest for risankizumab (SUCRA: 98.5%) and bimekizumab (83.8% for dosing every 4 weeks [Q4W], 72.7% for dosing Q4W then every 8 weeks). The PASI response rates did not differ significantly between risankizumab and the two bimekizumab regimens. Additionally, risankizumab was associated with significantly higher PASI response rates than brodalumab, guselkumab, ixekizumab, secukinumab, ustekinumab, adalimumab, and etanercept. In the safety NMAs (N = 8 RCTs), risankizumab had the highest relative rankings for all three outcomes (SUCRA: 92.1%, 82.0%, and 91.0% for any AE, any SAE, and AEs leading to treatment discontinuation, respectively). Risankizumab had a significantly lower rate of any AE than bimekizumab, ustekinumab, and secukinumab.ConclusionsRisankizumab was associated with the most favorable long-term benefit-risk profile for the treatment of moderate-to-severe plaque psoriasis. Although ixekizumab and bimekizumab had favorable efficacy profiles, both treatments had lower rankings for safety outcomes.

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: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:IntroductionNew generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited.ObjectivesTo compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis.MethodsA systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken.ResultsSeventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses.ConclusionsIn the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.

Dataset Information

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

Background

Objective

Methods

Results

Conclusion

Publications

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

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