Arisvia Sukma Hariftiyani

Inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis, involve chronic inflammation of the digestive tract. The incidence of IBD has been increasing globally, posing a growing burden despite advancements in treatment. Novel therapies targeting adhesion molecules such as MAdCAM-1 show promise by specifically inhibiting lymphocyte infiltration into the gut, potentially offering safer and more effective treatment options. This meta-analysis and systematic review were conducted to provide efficacy and safety analysis of ontamalimab for IBD treatment. Dose-response (DRMA), network (NMA), and random effect meta-analysis were conducted to extract clinical response, clinical remission, biomarker change, and adverse events of ontamalimab. Studies were retrieved from PubMed, Cochrane, and EMBASE to describe the pooled risk ratio (RR) and heterogeneity was determined if I2 >50%. RoB2 tool and ROBINS-I were used to assess risk of bias in RCT and clinical trial studies, respectively. The result was considered significant if p<0.05. A total of 670 studies were screened, resulting in 8 multicentre studies. There were significant differences in clinical response (RR: 1.39; 95%CI: 1.12–1.73; p = 0.003; I2= 35%), clinical remission (RR: 1.72; 95%CI: 1.17–2.53; p=0.006; I2= 26%), mean change of FC (RR: 624.29; 95%CI: 543.28-705.29; p<0.001; I2= 0%), mean change of CRP serum (RR: 9.71; 95%CI: 7.12–12.3; p<0.001), and mean MAdCAM-1 serum level (RR: 235.57; 95%CI: 203.80–267.33; p <0.001) between ontamalimab 75 mg and placebo after 12 wk of treatment. Meanwhile, adverse events from both groups were similar to those observed in patients treated with either placebo or ontamalimab. This study concluded that ontamalimab 75mg demonstrated significant efficacy in treating IBD, achieving superior outcomes in clinical response and clinical remission compared to placebo. Importantly, no cases of PML and significant adverse events were detected, indicating a favorable safety profile relative to other anti-MAdCAM-1 therapies.

Coronary artery disease (CAD) is a disease characterized by atherosclerosis formation which causes sudden cardiac death. The prevalence of CAD is expected to increase by 2030. Atherosclerosis started from accumulation of LDL in the blood vessels, followed by endothelial cell activation and dysfunction. PCSK9 is a gene that plays an important role in the creation of atherosclerotic plaque through induced degradation of LDLRs. Inhibition of PCSK9 gene resulted in a decrease of LDLRs degradation and reduction in LDL-C levels. LRP6, as well as its mutation, is a coreceptor that contributes to atherosclerosis through the canonical Wnt/β-catenin pathway. By employing EMPs mediated miRNA-126, third-generation antisense against miR-494-3p (3 GA-494), and recombinant Wnt mouse Wnt3a (rmWnt3a), the inhibition of LRP6 could reduce VSMCs proliferation, enhancing anti-inflammatory macrophages, and diminished bioactive lipids component, respectively. Those mechanisms lead to the stabilization and reduction of atherosclerosis plaques.