Brodalumab 210mg/1.5ml solution for injection pre-filled syringes

BackgroundPyoderma gangrenosum (PG) is a rare disease causing painful skin ulcers, typically starting with tender pustules that quickly develop into painful ulcers. Traditional treatments like glucocorticoids and immunosuppressants often have adverse effects and limited efficacy, making them unsuitable for all patients. Recent evidence shows that biological agents are more effective and safer, leading to increased acceptance. However, selecting the most suitable biological agent from the many available options remains a significant challenge for both physicians and patients.ObjectiveTo systematically review the treatment outcomes of two biologics: TNF (tumour necrosis factors)-α inhibitors and IL (interleukin) inhibitors in pyoderma gangrenosum.MethodsA search of Pubmed was conducted on September 7, 2024. A total of 107 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.ResultsA total of 139 patients were included. Ninety-two were treated with TNF-α inhibitors and 47 with IL inhibitors. The number of included cases and the efficacy are Infliximab (n=52, 88.4%), Adalimumab (n=23, 91.3%), Etanercept (n=13, 84.6%), Certolizumab (n=3, 66.6%), Golimumab (n=1, 100.0%), Anakinra (n=11, 100.0%), Canakinumab (n=7, 100.0%), Secukinumab (n=5, 40.0%), Brodalumab (n=3, 100.0%), Ixekizumab (n=1, 100.0%), Ustekinumab (n=12, 100.0%), Spesolimab (n=3, 100.0%), Guselkumab (n=2, 100.0%), Tildrakizumab (n=2, 100.0%), Risankizuma (n=1, 100.0%). Among them, 46.0% (n=64) achieved complete remission, including 47 (33.8%) who used TNF-α inhibitors and 17 (12.2%) with IL inhibitors. And the total effective rate of IL- inhibitors (93.6%) was higher than that of TNF-α inhibitors (88.0%), but had no statistical significance (p>0.05). However, it takes less time for IL inhibitors to reach partial remission or complete remission. Additionally, in infliximab group, the number of adverse events that occurred was large and varied.ConclusionDifference in effective rate shows no statistical significance between two kinds of agents. However, IL inhibitors demonstrate an advantage with shorter treatment cycles. Additionally, Infliximab has a wider range of side effects and should be used with caution.PROSPERO number: CRD42024608039.

Abstract licence: CC BY-NC

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.

Abstract licence: CC BY

IntroductionPsoriasis is a chronic, inflammatory skin disease that significantly impairs patients' quality of life (QOL). Several biologics with varying mechanisms of action are approved for treating moderate-to-severe plaque psoriasis (PSO) in Japan; bimekizumab is the only one that selectively binds to and inhibits interleukin (IL)-17F in addition to IL-17A. However, there is currently no recommended biologics treatment sequence, and their high cost limits treatment accessibility. This study evaluated bimekizumab cost-effectiveness versus IL-23 inhibitors in patients with PSO in Japan from a public healthcare payer's perspective, and explored variables that affect cost-effectiveness.MethodsA cohort simulation, lifetime Markov model with 2-week cycles simulated the treatment pathway in adults with moderate-to-severe PSO who had an inadequate response to previous treatments. Bimekizumab was compared with the IL-23p19 inhibitors guselkumab, risankizumab, and tildrakizumab in the first line; brodalumab was the second-line treatment for all arms. Transition to second-line treatment was triggered by not achieving a ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75), or discontinuation due to adverse events. A network meta-analysis provided PASI response rates. QOL scores were derived from EuroQol 5-Dimension 3-Level health questionnaire responses from global bimekizumab phase 3 studies. Drug and management costs were estimated on the basis of Diagnosis Procedure Combination-based data in Japan; 2%/year discounting was applied to costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated, and sensitivity and scenario analyses performed.ResultsBimekizumab generated the highest number of QALYs and was cost-effective against all IL-23 inhibitor comparators at a willingness-to-pay threshold of ¥5,000,000/QALY (bimekizumab versus guselkumab: ¥3,202,863/QALY; risankizumab: ¥4,732,268/QALY; tildrakizumab: ¥4,950,972/QALY). ICERs were sensitive to QOL scores, with PASI 100 QOL score being a key cost-effectiveness driver.ConclusionsFindings of the cost-effectiveness of bimekizumab against IL-23 inhibitors support the potential consideration of bimekizumab as a first-line treatment for moderate-to-severe PSO in Japan.

Abstract licence: CC BY-NC