Evaluating Interleukin-Driven Soft Tissue Response in Clear Aligners and Fixed Appliances: A Schematic Study and Meta-Analysis

Background: Orthodontic appliances have been known to affect periodontal health; this is because they have been shown to change the amount of plaque and local inflammatory response. This review tried to compare the periodontal condition and gingival crevicular fluid (GCF) cytokine concentration in individuals using clear aligners and fixed orthodontic anchors. Methods: A meta-analysis and systematic review of studies was done by searching the databases (PubMed, Scopus, Web of Science, Cochrane Library) to determine the number of research articles published until 2025. Clinical studies with observational studies comparing periodontal clinical outcome indexes and cytokine levels (e.g., IL-1, TNF-alpha) in patients with clear aligners and fixed appliances were obtained. Extracted data were analyzed, the risk of bias was calculated using Newcastle-Ottawa scale and Cochrane risk of bias tool, and a random-effects meta-analysis was done using RevMan 5.4.1. A 95% confidence interval (CI) of the standardized mean difference (SMD) was also computed. Results: Six studies with 237 participants were found that fit the inclusion criteria. The meta-analysis showed that patients who used clear aligners had a much-reduced level of pro-inflammatory cytokines when compared to the level of the same in the fixed appliances group. Furthermore, clinical values such as plaque index, gingival index, and bleeding on probing were better in the clear aligner group. Discussion: Clear aligners can be periodontally beneficial as they generate reduced tissue inflammation rates or clinical periodontal outcomes in comparison with fixed appliances in the course of orthodontic treatment. The small size of well-conducted studies and the implications of measurement methods of cytokines might have an influence on the generalizability of research results.