Ayyad, Mohammed

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). Study Question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? Data Sources: MEDLINE, Embase, Scopus, and Cochrane databases. Study Design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

Background: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Polypills, containing various combinations of medications for primary and secondary CVD prevention, have been developed to enhance medication adherence and reduce the healthcare burden of CVD. However, their effectiveness compared to usual care remains uncertain. Objective: This meta-analysis aimed to evaluate the effects of polypills on cardiovascular risk factors, major adverse cardiovascular events (MACE), and medication adherence. Methods: We conducted a comprehensive search for large-scale randomized controlled trials and observational studies comparing the effects of polypills versus usual care on CVD risk factors and events. Outcomes included changes in systolic and diastolic blood pressure (SBP, DBP), lipid profiles, occurrence of MACE, and medication adherence. Results: The use of polypills led to a statistically significant yet clinically modest reduction in SBP (mean difference -1.47 mmHg, 95% CI: -2.50 - -0.44, p<0.01) and DBP (mean difference1.10 mmHg, 95% CI: -1.68 - -0.51, p< 0.01) compared to usual care. Polypills also showed a significant reduction in the risk of MACE (RR: 0.86, 95% CI: 0.77 -0.95, p<0.01). There was a non-significant reduction in LDL and HDL levels. Adherence to medication improved by up to 17% in polypill users compared to those on usual care (p < 0.01). A multivariable metaregression analysis suggested that adherence may be the underlying factor responsible for the observed effect of the polypills on blood pressure. Conclusion: Polypills were found to significantly reduce SBP, DBP and MACE. An improvement in medication adherence was also observed among polypill users, which might be responsible for the significant reduction in SBP observed users. Future research might benefit from exploring a more personalized approach to the composition of polypills, which could reveal a more clinically significant impact of increased adherence on CVD outcomes.