Canakinumab 150mg powder for solution for injection vials

Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease (PAD), driven by both advanced atherosclerosis and chronic inflammation. Despite advancements in revascularization and medical therapy, outcomes remain poor. Inflammation has emerged as a key therapeutic target, and several anti-inflammatory agents are under investigation for potential benefit in CLTI. A comprehensive literature review was conducted using PubMed, Scopus, Embase, Google Scholar, and Web of Science to identify studies published between 1990 and 2025. Keywords included "chronic limb-threatening ischemia," "peripheral artery disease," "colchicine," "canakinumab," "methotrexate," "NLRP3 inflammasome," and "anti-inflammatory therapy." Eligible studies included original research, clinical trials, systematic reviews, and relevant guidelines focused on inflammation-targeted interventions in atherosclerosis and limb ischemia. Colchicine has shown significant reductions in major adverse cardiovascular events in large trials and retrospective PAD studies, though no randomized controlled trials (RCTs) have specifically addressed CLTI. Canakinumab reduced inflammatory biomarkers and improved walking performance in PAD but had no effect on plaque progression. Methotrexate did not demonstrate cardiovascular benefit in the Cardiovascular Inflammation Reduction Trial. Preclinical agents targeting the NLRP3 inflammasome (e.g., MCC950) have shown anti-inflammatory effects but lack human data. Nutraceuticals, including omega-3 fatty acids and polyphenols, may offer adjunctive benefits, though evidence remains limited. Inflammation-modulating therapies hold promise as adjuncts in CLTI management, potentially improving outcomes by targeting the underlying immune mechanisms of disease progression. However, current evidence is insufficient for clinical adoption in CLTI. Large-scale, well-designed RCTs focusing on limb-specific outcomes are necessary to clarify the role of these therapies in high-risk vascular populations.

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BackgroundFor advanced non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) expression MethodsPubMed, Ovid Medline, the Cochrane Library, and Embase were searched from database inception to August 15, 2025, to identify phase III randomized controlled trials (RCTs) that explored first-line treatments in treatment-naïve advanced NSCLC, PD-L1 ResultsTwenty-five phase III RCTs involving 5,815 participants were eligible. Overall, 21 first-line treatments were identified. In terms of OS, pembrolizumab + chemotherapy + canakinumab (Pembro-chemo-canakinumab) (SUCRA =0.90) showed great potential in improving outcomes, although its long-term efficacy still needed to be validated. Nivolumab + ipilimumab (Nivo-ipi) (SUCRA =0.78) closely followed. Both top regimens showed non-significant superiority over Pembro-chemo. Regarding PFS, nivolumab + chemotherapy + bevacizumab (SUCRA =0.88), and serplulimab + chemotherapy (SUCRA =0.87) were the optimal regimens. Specifically for non-squamous patients, Pembro-chemo was optimal for OS (SUCRA =0.90), followed by Nivolumab + chemotherapy + bevacizumab (SUCRA =0.82). Nivolumab + chemotherapy + bevacizumab optimized PFS, with an hazard ratio (HR) of 0.52 [95% confidence interval (CI): 0.30-0.92 vs. Pembro-chemo]. For squamous patients, nivolumab + ipilimumab ± chemotherapy (Nivo-ipi-chemo) led in OS, while serplulimab + chemotherapy in PFS.ConclusionsFirst-line personalized treatment for PD-L1 <1%, advanced NSCLC should be histology-based, balancing efficacy and toxicity. Pembro-chemo and nivolumab + chemotherapy + bevacizumab combinations are recommended as the optimal first-line options for non-squamous patients, and Nivo-ipi-chemo for squamous patients.

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BackgroundInflammation is causally implicated in the development and progression of atherosclerotic cardiovascular disease, but clinical trials of anti-inflammatory therapies have yielded inconsistent effects on cardiovascular outcomes.MethodsWe conducted a systematic review and meta-analysis to evaluate the cardiovascular efficacy and safety of a broad range of anti-inflammatory agents. Medline, Embase and Cochrane databases were searched from inception to 08 October 2024 for randomised controlled trials evaluating the effect of anti-inflammatory therapies on a primary cardiovascular outcome with at least 100 patient-years follow-up per treatment arm. Trial level meta-analysis was performed using a random effects model. The primary outcome was major adverse cardiovascular events (MACE); other outcomes included myocardial infarction, stroke, heart failure, serious adverse events, infection, and malignancy.ResultsThirteen trials enrolling 82,208 participants were included. The effect of anti-inflammatory agents on MACE varied by drug class (P-heterogeneity=0.049), driven primarily by benefits observed with colchicine (RR 0.76; 95 % CI 0.65-0.90; moderate certainty) and canakinumab (RR 0.88; 95 % CI 0.79-0.97; moderate certainty), with no benefit observed for other agents. Among colchicine trials, heterogeneity was identified (P-heterogeneity=0.003), and subgroup analyses suggested greater benefit in coronary artery disease and/or recent myocardial infarction trials (P-heterogeneity=0.068). Safety outcomes also varied by drug class, with significant heterogeneity in serious adverse events (P-heterogeneity=0.005), largely attributable to methotrexate, and some evidence of heterogeneity for infection (P-heterogeneity=0.076) and malignancy (P-heterogeneity=0.077).ConclusionSome anti-inflammatory agents may reduce the risk of cardiovascular outcomes, but their effects appear to vary substantially across drug classes, with important differences in both efficacy and safety. These findings underscore the need for rigorous evaluation of new anti-inflammatory therapeutics to ascertain benefits and harms across different populations and therapeutic indications.

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BackgroundLung cancer remains a leading cause of cancer-related mortality worldwide, with few effective treatment options available for advanced stages. Canakinumab, an IL-1β inhibitor, has been investigated as a potential therapeutic agent due to its role in modulating tumor-promoting inflammation. However, its clinical efficacy and safety in NSCLC (non-small cell lung cancer) continue to be uncertain.AimsWe aimed to evaluate the efficacy and safety of canakinumab compared with other standard therapies in NSCLC treatment.Methods and resultsA systematic review was conducted in accordance with PRISMA guidelines. Four electronic databases (PubMed, Scopus, Web of Science, and Embase) were searched for clinical trials assessing canakinumab for NSCLC. Eligible studies included phase I-III clinical trials. The Synthesis Without Meta-analysis (SWiM) guidelines were followed due to substantial heterogeneity in studies. Outcomes evaluated included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), major pathologic response (MPR), and treatment-related adverse events. Five clinical trials (three phase III, one phase II, and one phase IB) met the inclusion criteria, with sample sizes ranging from 88 to 1382 patients. The included studies evaluated canakinumab in four distinct clinical settings: adjuvant therapy after complete resection (CANOPY-A), first-line treatment in combination with pembrolizumab plus chemotherapy (CANOPY-1) or spartalizumab plus chemotherapy, second-line treatment in combination with docetaxel (CANOPY-2), and neoadjuvant therapy with or without pembrolizumab (CANOPY-N). Compared to standard therapies, canakinumab did not significantly improve ORR, PFS, OS, or MPR across any clinical setting. Safety analysis showed comparable adverse event rates between intervention and control groups.ConclusionDespite its promising mechanistic rationale, Canakinumab did not show significant clinical benefits in NSCLC. Although it is generally well tolerated, its role in NSCLC treatment remains uncertain. Future research should concentrate on identifying predictive biomarkers and optimizing combination strategies to enhance its therapeutic potential.

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