Guselkumab for the Treatment of Moderate-to-Severe Plaque Psoriasis During Induction Phase: A Systematic Review and Network Meta-Analysis

Abstract

Background: Guselkumab is an interleukin-23 inhibitor indicated for treatment of moderate-to-severe plaque psoriasis. Objective: The objective was to determine the relative efficacy and safety of guselkumab compared to other biologics. Methods: A systematic review was performed to identify randomized controlled trials (RCTs). Bayesian network meta-analyses (NMAs) were conducted using meta-regression analyses that adjusted for cross-trial differences and risk differences. The primary outcome was Psoriasis Area and Severity Index (PASI) 90 response. Other efficacy and safety outcomes were considered. Several meta-regressions were performed to account for variations in patient and study characteristics: baseline risk adjustment (ie, control group response), prior biologic use, duration of psoriasis, weight, age, race, and baseline PASI/dermatology life quality index scores. The best-fitting model using predefined criteria was selected. Results: Forty-five RCTs were identified. Patient and study characteristics differed between RCTs as reflected in variations in control group response. Both the baseline risk-adjusted NMA and the risk-difference NMA fit the data best and suggested guselkumab has one of the highest PASI 90 responses. Pairwise comparisons from the baseline risk-adjusted PASI 90 NMA suggested guselkumab has comparable efficacy with ixekizumab (relative risk [RR]: 0.999, 95% credible intervals [CrIs]: 0.89-1.13) and brodalumab (RR: 1.04, 95% CrIs: 0.91-1.17) and superior efficacy versus all other treatments in the network (RR range, 1.20 to 43.22). Guselkumab was superior or comparable to other therapies for other efficacy outcomes and had a more favorable safety profile than most. Conclusions: Guselkumab has one of the highest PASI 90 responses among psoriasis treatments; similar findings were observed for other efficacy outcomes. Guselkumab has a favorable benefit-risk balance compared to moderate-to-severe psoriasis therapies.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response

“…Adjusting for differences in the placebo arms may account for heterogeneity between trials and could improve the model fit [42, 48–50]. This approach has previously been used in other NMAs comparing the efficacy of biological treatments for moderate-to-severe psoriasis [38, 51] and has been recommended by NICE in recognition of the variability in placebo response across trials [52]. Analyses adjusting and not adjusting for cross-trial variation in placebo-arm responses were carried out using random-effects assumptions and assessed for their goodness of fit.…”

“…These include guselkumab, tildrakizumab, and risankizumab [26–29]. Although data from clinical trials has shown these treatments to be more efficacious than anti-TNFs and ustekinumab [30–36], clinical trial data on their benefit compared to the more established IL-17 inhibitors is very limited [37, 38]. Rapid developments in the field of psoriasis treatments necessitate assessment of the efficacy of new drugs relative to older treatments and different drug classes.…”

Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year

“…In recent years, the number of treatments available for moderate-to-severe psoriasis has increased, enabling dermatologists to optimize therapy for patients to achieve better outcomes (8); however, choosing between therapies can be challenging. Numerous network meta-analyses (NMAs) that have investigated psoriasis therapies over the first 10 to 16 weeks of treatment have been published (9)(10)(11)(12)(13)(14) and yet only two reviews have quantitatively assessed the long-term efficacy of psoriasis therapies: one at 6 months (15) and another at 1 year (16). Since these studies were published, four new treatments have been licensed for psoriasiscertolizumab pegol, guselkumab, tildrakizumab, and risankizumab.…”

Targeted therapy of psoriasis: inhibition of the IL-23 signaling pathway — evidence from clinical studies and real practice

“…Гуселькумаб является первым представителем класса ингибиторов ИЛ-23 и имеет ряд преимуществ перед существующей терапией. По данным метаанализа гуселькумаб превосходит по эффективности в краткосрочной и, что особенно важно, в долгосрочной перспективе большинство ГИБП, в том числе ингибиторы ФНО-α, секукинумаб, устекинумаб [21,26].…”

“…С целью оценки сравнительной эффективности и безопасности гуселькумаба по сравнению с другими ГИБП в индукционном периоде (10-16 недель) был проведен систематический обзор и сетевой метаанализ [21]. Согласно результатам анализа 45 РКИ с включением 24 515 пациентов гуселькумаб превосходит в эффективности адалимумаб, этанерцепт, инфликсимаб, апремиласт, устекинумаб, тилдракизумаб и секукинумаб; препарат имеет благоприятное соотношение пользы и риска по сравнению с другими разрешенными к применению лекарственными средствами для лечения тяжелого и среднетяжелого псориаза.…”