Influence of anti-rheumatic agents on the periodontal condition of patients with rheumatoid arthritis and periodontitis: A systematic review and meta-analysis

Objective To evaluate the influence of diverse anti-rheumatic agents on the periodontal condition and to provide clinical medication guidance for patients with rheumatoid arthritis (RA) and periodontitis. Background In recent years, the correlation between RA and periodontitis has become a hot research topic, but no medication recommendations for patients with RA and periodontitis are available at present. Methods The protocol of this review was registered in advance with PROSPERO (CRD42021248827). Electronic search and manual searches up to March 20, 2021 were conducted. The inclusion criteria for the studies were as follows: included patients diagnosed with periodontitis and RA submitted to anti-rheumatic agent therapy; with a control group receiving no anti-rheumatic agent therapy; with outcomes including at least one periodontal parameter. Probing depth (PD) and clinical attachment loss (CAL) were pooled using weighted mean difference (WMD) and 95% confidence intervals (CI) while gingival index (GI)/modified gingival index (MGI) was analyzed by standardized mean difference (SMD) and 95% CI. Results One thousand four hundred and seventy-eight studies potentially related to the aim of this review were screened, but only 463 patients from 14 studies were included in the qualitative analysis, and 146 patients from 4 studies were included in the meta-analysis. Statistically significant reductions were observed among the subjects who received anti-rheumatic agents for PD [WMD = -0.20; 95% CI (-0.33, -0.07); effect p = .003; I-2 = 50%; p = .11], CAL [WMD = -0.4; 95% CI (-0.66, -0.15); effect p = .002; I-2 = 57%; p = .07] and GI/MGI [SMD = -0.61;95% CI (-0.94, -0.27; effect p = .0004; I-2 = 26%; p = .25]. Consistent with the above results, this systematic review produced promising results that PD, CAL, GI/MGI, and bleeding on probing (BOP) decreased when patients with RA and periodontitis were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), anti-B lymphocyte agents, anti-IL-6R agents, or JAK inhibitors. PD and CAL declined after the administration of anti-TNF-alpha agents; most studies reported decreased GI/MGI and BOP, while 2 studies reported increased GI/MGI and BOP. Conclusions These results revealed that csDMARDs, anti-B lymphocyte agents, anti-IL-6R agents, anti-TNF-alpha agents, and JAK inhibitors had potential positive effects in improving the periodontal condition of patients with RA and periodontitis. However, future research is needed to elucidate whether anti-TNF-alpha agents have a side effect of increased gingival inflammation.