Guselkumab 45mg/0.45ml solution for injection pre-filled disposable devices

Background . The 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. Objective . To 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). Methods . A 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). Results . This 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%). Conclusions . IL-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.

Abstract licence: CC BY 4.0

BackgroundInterleukin (IL)-23 inhibitors-including IL-23p19 inhibitors (guselkumab, mirikizumab, risankizumab) and the IL-12/23p40 inhibitor ustekinumab-are emerging treatments for Crohn's disease (CD), but comparative data among them remain limited. Most previous network meta-analyses (NMAs) compared IL-23 inhibitors with other biologic classes or examined a specific IL-23 inhibitor against multiple comparators, often excluding some trials due to design heterogeneity or publication timing. Safety outcomes were also underreported. We conducted the first comprehensive NMA focused exclusively on IL-23 inhibitors to provide practice-oriented evidence.MethodsWe systematically searched PubMed, Embase, and Cochrane CENTRAL on May 11, 2025, for randomised controlled trials (RCTs) comparing guselkumab, mirikizumab, risankizumab, or ustekinumab in adults with moderate-to-severe CD. We analysed induction (weeks 8-12) and maintenance (weeks 48-64) phases, evaluating approved regimens in the main analysis and all reported regimens in a secondary analysis. Outcomes were clinical and endoscopic efficacy, adverse events, and serious adverse events.ResultsFourteen RCTs (induction phase n = 4,834, maintenance phase n = 3,632) were included, enrolling adults with moderate-to-severe CD (mean age 35-40 years; 40-60% male; baseline Crohn's Disease Activity Index [CDAI] around 300). Guselkumab showed the highest induction efficacy among IL-23 inhibitors and versus placebo but had the greatest risk of adverse events than placebo during maintenance. Mirikizumab had the lowest risk of serious adverse events across both phases. Risankizumab ranked highest for endoscopic outcomes with a balanced efficacy-safety profile. Ustekinumab showed modest effects. The differences in efficacy and safety may be interpreted in relation to variations in Fc structure and IgG subclass.ConclusionsThis is the first NMA comparing IL-23 inhibitors using contemporary evidence. The results offer practical insights for personalized CD treatment: guselkumab may be preferred for rapid response, mirikizumab for safety, and risankizumab for balanced efficacy.

Abstract licence: CC BY-NC

IntroductionRecent trials with withdrawal arms in patients with psoriasis have highlighted the need for updated clinical guidance. The aim of this investigation was to compare the effects and safety of planned limited-time withdrawal versus continuous maintenance of interleukin (IL) inhibitors in patients with psoriasis.MethodsOn August 5, 2025, the following platforms were systematically searched: PubMed, Embase, Clarivate (Web of Science), Scopus, and Ovid. Titles and abstracts, followed by full-text articles, were independently screened by two reviewers, with any disagreements being resolved by a third reviewer. Certainty of evidence was evaluated via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Network meta-analyses for the Psoriasis Area and Severity Index (PASI) 90 and PASI100 outcomes were performed. The risk ratio (RR) of relapse was ranked using the surface under the cumulative ranking curve (SUCRA) metric.ResultsA total of 7444 records were retrieved, 54 of which included data from 18 different trials. The data revealed a total of 2995 patients who were subjected to anti-IL withdrawal regimens that were eligible for comparison with anti-IL maintenance. For the PASI90 outcome, the network meta-regression, adjusted for a post-withdrawal follow-up duration of 40-48 weeks, indicated that bimekizumab demonstrated a RR for relapse (RR 5.36; 95% confidence interval (CI) 3.45-8.34; SUCRA 0.685) comparable to that of guselkumab (RR 7.45; 95% CI 4.97-11.19; SUCRA 0.412) and lower than that of ixekizumab (RR 17.45; 95% CI 10.22-29.80; SUCRA 0.006). No significant difference in adverse event rates was observed between the anti-IL withdrawal and maintenance groups.ConclusionsCompared with continued treatment, planned withdrawal of anti-IL therapy is associated with a largely superior risk of relapse, without any reduction in the incidence of adverse events. Moreover, bimekizumab withdrawal demonstrated better outcomes than ixekizumab withdrawal did according to the PASI90 outcome.Study registrationThis study was prospectively registered on PROSPERO (identification number CRD420251118724).

Abstract licence: CC BY-NC