PURPOSE: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis. METHODS: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria. RESULTS: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-alpha therapy in RA subjects with periodontitis have yielded inconsistent results. CONCLUSIONS: There are limited data, however, to suggest that anti-TNF-alpha agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.