Guselkumab 100mg/1ml solution for injection pre-filled disposable devices

Abstract Background Accumulating evidence demonstrates the efficacy of interleukin-23 (IL-23) p19 inhibitors and small molecule drugs in the treatment of Crohn's disease (CD), with several agents advancing toward regulatory approval. This study aimed to compare the efficacy and safety of IL-23p19 inhibitors and small molecule drugs as induction therapy in CD. Methods Literature searches were updated to August 2025. Efficacy endpoints included clinical remission, endoscopic improvement/remission. Safety analysis focused on adverse events and serious adverse events. Employing a frequentist framework, we calculated surface under the cumulative ranking (SUCRA) scores for treatment rankings (higher SUCRA indicates better efficacy/safety). Exploratory subgroup analyses were conducted based on prior biologic failure. Results 11 RCTs met inclusion criteria. Subcutaneous guselkumab (SUCRA 93.2%), intravenous guselkumab (88.9%) and risankizumab (72.0%) emerged as the top-ranked agents for inducing clinical remission. Particularly, guselkumab ranked highest in both patients with prior biologic failure (96.3%) and without prior biologic failure (91.2%). Upadacitinib ranked highest for inducing endoscopic improvement (96.2%), patient-reported outcomes remission (91.1%) and endoscopic remission (92.2%). Safety analysis revealed that risankizumab ranked highest for both adverse events (81.5%) and serious adverse events (92.1%), whereas upadacitinib ranked lowest for adverse events (8.4%) and filgotinib 100mg ranked lowest for serious adverse events (11.2%). Conclusions Guselkumab represents a particularly favorable option for inducing clinical remission in CD, irrespective of prior biologic failure. Based on a comprehensive comparison of multiple outcomes, both guselkumab and upadacitinib are recommended as second-line therapies for CD. IL-23p19 inhibitors exhibited a more favorable safety profile than upadacitinib in CD management.

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Background: Guselkumab, a selective anti-IL-23p19 monoclonal antibody, has shown high efficacy in randomized trials for moderate-to-severe psoriasis and active psoriatic arthritis (PsA). Real-world evidence is essential to assess treatment performance in broader and more heterogeneous patient populations. Objectives: To synthesize the available real-world evidence on the effectiveness and safety of guselkumab in psoriasis and PsA, and to quantify pooled clinical responses across clinically relevant follow-up windows. Methods: A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, MEDLINE, and Web of Science were searched for observational real-world studies of guselkumab in adults with psoriasis and/or PsA. Primary pooled outcomes were PASI 90 and PASI 100 in psoriasis and DAPSA Results: Thirty-four studies were included (29 psoriasis, 5 PsA). In psoriasis, pooled PASI 90 response rates were 50.8% (95% CI 46.8-54.8) at 12-16 weeks, 68.4% (95% CI 66.3-70.4) at 20-28 weeks, 71.2% (95% CI 64.9-76.8) at 36-60 weeks, and 77.1% (95% CI 74.9-79.3) at ≥96 weeks. Pooled PASI 100 response rates were 49.8% (95% CI 47.5-52.2) at 20-28 weeks and 49.7% (95% CI 47.1-52.3) at 36-60 weeks. In PsA, pooled DAPSA Conclusions: Real-world evidence supports guselkumab as an effective treatment for psoriasis and a clinically useful option for PsA, with a safety profile broadly consistent with the known trial experience. Interpretation remains limited by observational designs, heterogeneous denominators, and inconsistent safety reporting.

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IntroductionPsoriasis, a chronic inflammatory skin condition, affects 125 million worldwide. Current treatments provide symptomatic relief but face limitations. Guselkumab shows promise for moderate-to-severe psoriasis.ObjectiveWe aimed to conduct a systematic review and meta-analysis exploring the safety and efficacy of guselkumab in moderate-to-severe psoriasis.MethodsWe searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials (RCTs) comparing guselkumab to placebo in moderate-to-severe psoriasis.Primary endpointsInvestigators' Global Assessment (IGA) 0, Psoriasis Area and Severity Index (PASI) 90, and ≥1 adverse event (AE). Secondary endpoints: IGA 0/1, PASI75, PASI100, Dermatology Life Quality Index (DLQI), and ≥1 severe AE. RStudio was used for statistical analyses.ResultsWe included 1607 patients from 6 RCTs. Guselkumab significantly increased odds of IGA 0 (odds ratio (OR) OR: 73.87; 95% confidence interval (CI): 32.53-167.73; P2=0.0%), and IGA 0/1 (OR) OR: 54.84; 95% CI: 24.72-121.64; P2=60.1%). Also, the OR of PASI75 (OR: 58.42; 95% CI: 23.03-148.17; P2=70.0%), PASI90 (OR: 46.47; 95% CI: 14.23-151.76; P2=71.7%), and PASI100 (OR: 59.27; 95% CI: 23.17-151.61; P2=0.0%) were higher with guselkumab. DLQI change was greater with guselkumab (MD: -8.46; 95% CI: -10.31 - -6.62; P2=77.8%). No significant difference in AEs and severe AEs between guselkumab and placebo (OR: 0.92; 95% CI: 0.68-1.24; P=0.58; I2=30.9%), (OR: 1.19; 95% CI: 0.54-2.64; P=0.66; I2=0.0%). Leave-one-out analysis identified PROTOSTAR as a source of heterogeneity. Subgroup analysis showed higher IGA 0 and PASI90 ORs in adults than in adolescents/children, with no dosage-based differences in PASI90 or AE.ConclusionThis meta-analysis suggests that guselkumab does significantly improve moderate-to severe psoriasis, without a significant increase in AEs.

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This study used network meta-analysis (NMA) to evaluate the comparative efficacy of available advanced therapies for moderately to severely active Crohn’s disease (CD) versus the IL-23 inhibitor guselkumab. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of advanced therapies in moderately to severely active CD. Bayesian NMAs were conducted for outcomes of clinical response, clinical remission, endoscopic response, and a combined outcome of clinical remission with endoscopic response, at the end of the maintenance phase (up to 1 year). Primary analyses included patients with varied prior inadequate treatment responses, with additional analyses conducted for specific subgroups. Re-randomized trials were normalized in several cases to mimic a standard treat-through design, incorporating data from additional sources, when necessary, for patients who had an inadequate response or experienced a delayed response following induction. Of the 58 RCTs identified, 13 with maintenance endpoint data were ultimately included in the NMAs. Guselkumab 100 mg and 200 mg were more likely to be effective versus several comparators. Guselkumab 200 mg demonstrated significantly greater efficacy versus infliximab 10 mg/kg every 8 weeks and upadacitinib 30 mg daily for clinical response and clinical remission. For endoscopic response, guselkumab 200 mg showed significantly greater efficacy than ustekinumab, adalimumab, and upadacitinib. Significance was also noted versus ustekinumab on the combined outcome of clinical remission with endoscopic response. Similarly, guselkumab 100 mg demonstrated efficacy versus comparators across analyses. Guselkumab achieved higher rankings based on surface under the cumulative ranking curve. Findings of primary analyses within mixed populations were generally corroborated by subpopulation analyses. Results of this NMA in moderately to severely active CD indicate a higher likelihood of guselkumab achieving each clinical and endoscopic endpoint analyzed at the end of the maintenance phase versus other advanced therapies assessed. A network meta-analysis (NMA) was completed to compare the effectiveness of advanced treatments for Crohn’s disease, a chronic inflammatory condition of the digestive tract. Our NMA focused on the drug guselkumab and how effective it is compared with other treatments for Crohn’s disease. We looked at 4 outcomes related to efficacy that are common in trials: clinical response (improvement in symptoms), clinical remission (disappearance of symptoms), endoscopic response (seen in the digestive tract), and a combined outcome of clinical remission with endoscopic response. Data were analyzed from trials lasting up to 1 year. Patients who had not responded well to prior treatments were included in the analysis. Thirteen trials met all criteria and were included in the analysis. Guselkumab at doses of 100 mg and 200 mg was more effective than several treatments. Guselkumab 200 mg was significantly better than infliximab and upadacitinib for both clinical response and clinical remission. It also showed better results than ustekinumab, adalimumab, and upadacitinib for endoscopic response and was more effective than ustekinumab for the combined outcome of clinical remission with endoscopic response. Our analysis shows that guselkumab is likely to be more effective at achieving both symptom improvement and healing the digestive tract compared with other advanced treatments for moderate to severe Crohn’s disease.

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BackgroundRecently, the literature has expanded with peer-reviewed studies on immunomodulatory agents' efficacy on scalp psoriasis-which, in turn, widened knowledge gaps regarding these agents' relative effectiveness. We determined the relative efficacy of immunomodulatory monotherapies for scalp psoriasis.MethodsWe ran Bayesian network meta-analyses (NMAs) using outcomes related to Psoriasis Scalp Severity Index (PSSI) and scalp-specific Physician's Global Assessment of clear (0) or almost clear (1) (Sc-PGA 0/1).ResultsWe estimated the relative efficacy of 22 interventions (including placebo), and analyzed 9 outcomes, namely: proportion of participants who attained Sc-PGA 0/1, proportion of participants who achieved 100% improvement in PSSI (PSSI-100), and proportion of participants who achieved 90% improvement in PSSI (PSSI-90) at 8, 12, and 16 weeks.ConclusionsWe are the first to provide comparative evidence on the efficacy of newly investigated agents such as deucravacitinib, tildrakizumab, roflumilast and icotrokinra. In general, the IL-17 inhibitors (bimekizumab, ixekizumab, secukinumab, brodalumab) and IL-23 inhibitors (icotrokinra, guselkumab, tildrakizumab) were effective depending upon the outcome and time-point being considered. At 16 weeks, for PSSI-100, ixekizumab 150 mg at weeks 0, 2, 4, 8, and 12 ranked highest; at 16 weeks, for Sc-PGA 0/1 bimekizumab 320 mg every 4 weeks ranked highest; at 8 weeks, for PSSI-100 ixekizumab 80 mg every 2 weeks ranked highest; at 8 weeks, for Sc-PGA 0/1 secukinumab 300 mg at weeks 1, 2, 3 and then every 4 weeks ranked highest. Small-molecule therapies (apremilast, deucravacitinib, roflumilast) improved scalp psoriasis modestly. Our work would guide the design of future studies and clinical decision-making.

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Multiple biologic agents targeting different inflammatory pathways are available for moderate-to-severe plaque psoriasis. While previous network meta-analyses have compared biologics, most were published before the approval of bimekizumab (the newest dual interleukin [IL]-17A/F inhibitor) and lack head-to-head comparisons incorporating this agent alongside other contemporary biologic therapies. We conducted a systematic literature search of PubMed and Clinical Trials to identify phase III randomized controlled trials comparing biologic treatments for moderate-to-severe plaque psoriasis. The primary outcome was achievement of 90% or greater reduction in Psoriasis Area and Severity Index (PASI 90) at week 16. We performed a frequentist random-effects network meta-analysis to estimate odds ratios (OR) with 95% confidence intervals (CI) for all treatment comparisons. From 642 records identified, 11 phase III randomized controlled trials (10 datasets, 6,657 patients) were included, comparing bimekizumab (IL-17A/F inhibitor), secukinumab (IL-17A inhibitor), risankizumab and guselkumab (IL-23p19 inhibitors), adalimumab (tumor necrosis factor-alpha inhibitor), ustekinumab (IL-12/23 inhibitor), and placebo. Compared with placebo, all active treatments showed significant efficacy: bimekizumab (OR 170.04, 95% CI 104.33-277.14), risankizumab (OR 95% CI 59.97-151.74), guselkumab (OR 82.25, 95% CI 51.23-132.03), secukinumab (OR 75.01, 95% CI 45.37-124.02), adalimumab (OR 30.07, 95% CI 19.16-47.18), and ustekinumab (OR 26.68, 95% CI 16.48-43.20). Network heterogeneity was low (I² = 0.0%) for most comparisons. Bimekizumab demonstrated the highest efficacy for achieving PASI 90 at week 16, followed by risankizumab, guselkumab, and secukinumab. All newer biologic agents showed substantial superiority over adalimumab and ustekinumab. These findings can inform treatment selection and guideline development for moderate-to-severe plaque psoriasis.

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