BACKGROUND:Risankizumab (RZB) is an anti-interleukin 23 (anti-IL-23) approved for the treatment of Crohn disease (CD). STUDY QUESTION:We aimed to evaluate the effectiveness and safety of RZB in the treatment of CD in real-world settings. STUDY DESIGN:We performed a retrospective review of a multicentre consortium of patients with CD treated with RZB. MEASURES AND OUTCOMES:Coprimary outcomes were clinical remission at week 12, 24, and 52 (Harvey-Bradshaw Index score of ≤4), and safety. Secondary outcomes included steroid-free clinical remission, clinical response, and endoscopic remission at 52 weeks. RESULTS:A total of 487 patients were included. The median follow-up was 24 (interquartile range: 16-38) weeks. A total of 372 (76.4%) patients achieved clinical remission at maximal follow-up. According to the treatment line in which RZB was administered, clinical remission occurred in 115/134 (85.8%) patients on second-line therapy, 112/153 (73.2%) on third-line therapy, and 145/200 (72.5%) on fourth-line therapy, with a significant difference ( P = 0.010). Adverse events occurred in 60 patients (12.6%) during follow-up; most of them were mild (50/60, 83.3%). Regarding the secondary outcomes: steroid-free clinical remission was achieved in 342 (71.8%) patients, and clinical response was observed in 443 (91.0%) patients. Six (1.2%) patients underwent surgery during follow-up. Mucosal healing was achieved in 34/67 (50.7%) patients. CONCLUSIONS:In this extensive, real-world study, RZB was effective and well tolerated in an advanced-therapy-exposed population of patients with CD and associated with favorable clinical and endoscopic outcomes.
BACKGROUND:Gonorrhea is a preventable and treatable infection caused by Neisseria gonorrhoeae , remaining a major public health concern because of antibiotic-resistant strains. A milestone was reached with zoliflodacin, the first therapeutic in its class in nearly 2 decades. MECHANISM OF ACTION, PHARMACODYNAMICS AND PHARMACOKINETICS:Zoliflodacin is a first-in-class spiropyrimidinetrione antibacterial agent that targets type II topoisomerases DNA gyrase and topoisomerase IV enzymes essential for DNA synthesis. Its primary target is the GyrB subunit of DNA gyrase, rather than the GyrA or ParC subunits affected by fluoroquinolones. The area under the concentration-time curve/minimum inhibitory concentration is the primary pharmacokinetics and pharmacodynamics index associated with bacterial killing. Zoliflodacin binds approximately 83% to plasma proteins, undergoes extensive metabolism through cytochrome P450-mediated and non-P450-mediated pathways, has a low urinary excretion with a major fecal route elimination pathway, and an elimination half-life of around 5-6 hours. CLINICAL TRIALS:Zoliflodacin demonstrated positive results for the treatment of uncomplicated urogenital gonorrhea in phase 2 and subsequently phase 3 trials. In a phase 2, multicenter, open-label RCT, the efficacy and safety of zoliflodacin was compared with ceftriaxone. Cure rates for urogenital infections were 96% (55/57) (2 g), 96% (54/56) (3 g), and 100% (28/28) (ceftriaxone). In a phase 3, multinational, open-label, noninferiority RCT, participants were randomly assigned (2:1) to receive a single 3 g oral dose of zoliflodacin or a single dose of 500 mg intramuscular injection of ceftriaxone plus 1 g oral azithromycin. The primary end point for microbiological cure was achieved in 90.9% (460/506) of patients on zoliflodacin compared with 96.2% (229/238) of the comparator, demonstrating noninferiority and good tolerability. THERAPEUTIC ADVANCE:Oral zoliflodacin represents a novel option for the treatment of uncomplicated urogenital gonorrhea, including antibiotic-resistant strains, providing an important alternative therapy.
BACKGROUND:Cardiovascular disease remains the leading cause of global mortality (19.8 million deaths in 2022; 32% of all deaths worldwide). Drug repurposing-extending approved agents beyond their original indications-has emerged as a high-impact strategy in cardiovascular prevention, offering reduced development timelines, established safety profiles, and faster implementation than de novo molecular development. STUDY QUESTION:Which repurposed cardiovascular agents demonstrate the most favorable pharmacoeconomic profiles, and how does the convergence of clinical benefit, patient risk stratification, and economic sustainability define the optimal hierarchy for cardiovascular prevention? STUDY DESIGN:Narrative review synthesizing evidence from 19 pivotal cardiovascular outcomes trials and European and American guidelines. No formal meta-analysis was applied. MEASURES AND OUTCOMES:For 13 agents across 8 therapeutic classes, efficacy was quantified as relative and absolute risk reductions, and as the number needed to treat or to harm. Pharmacoeconomic value was assessed via incremental cost-effectiveness ratio in US dollars per quality-adjusted life year, integrating mortality in years of life lost and morbidity in years lived with disability. Primary outcomes included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, and heart failure hospitalizations. RESULTS:Three Incremental Cost-Effectiveness Ratio (ICER) tiers were identified: Low-cost (< $20,000/ Quality-Adjusted Life Year (QALY)): ramipril (Number Needed to Treat (NNT) 28), carvedilol (NNT 29), metformin ( NNT 9-15, highest Relative Risk Reduction (RRR) 38-42%), and generic statins - robust mortality benefits at negligible cost; Moderate-cost ($3,000-$50,000/QALY): empagliflozin (↓38% cardiovascular mortality, NNT 61), dapagliflozin (NNT 20 in Heart Failure with Reduced Ejection Fraction), liraglutide (NNT 51), semaglutide (NNT 43), colchicine (NNT 36, morbidity benefit only), and branded statins; High-cost ($80,000-$300,000/QALY): Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors (evolocumab NNT 63; alirocumab NNT 64) - proven benefit compromised by unaffordable biologic pricing. CONCLUSIONS:Pharmacoeconomic stratification of repurposed cardiovascular agents identifies 3 distinct tiers. Generic agents-ramipril, carvedilol, metformin, and statins-demonstrate the most favorable cost-effectiveness profiles and should form the basis of any prevention protocol. SGLT2 inhibitors and GLP-1 receptor agonists offer clinically meaningful benefits in secondary prevention when applied to populations meeting pivotal trial eligibility criteria. PCSK9 inhibitors remain cost-effective only in patients with very high cardiovascular risk and inadequate LDL control on maximally tolerated statin therapy.
