Table 2.

Selected studies assessing the effects of intervention in subjects with RA and/or periodontitis

Authors	Study conditions	Treatment	Treatment outcome
Al-Katma et al. (72)	Case–control intervention study (8 weeks) RA defined by ACR criteria (53). Periodontitis defined by AAP criteria (6) To assess the effects of non-surgical periodontal therapy on RA.	Seventeen subjects with RA+ receiving periodontal treatment 12 subjects. with RA+ with no periodontal treatment. ***RA subjects on routine RA treatment (DMARDs). RA activity assessed by DASH 28 and ESR.	58.8% in the test group and 16.7% in the periodontally untreated group demonstrated improved RA scores.
Pers et al. (73)	Case–control study;40 subjects with RA RA defined by ACR criteria (53). Assessment of periodontal status BOP, PPD and CAL. Study purpose to assess the role of anti-TNF-α on periodontal status.	20 subjects received infliximab/methotrexate every 6 weeks for ≥22 months. 20 subjects (9 with periodontitis) were studied before and after receiving 9nine infusions of infliximab. No routine periodontal therapy was performed.	Plaque index and PPD were similar in both groups. BOP increased in infliximab group (p<0.001). Mean 0.4 mm decrease in CAL in infliximab-treated group.
Miranda et al. (74)	Case–control study of 17 RA and 17 healthy control age-, gender-, smoking-matched subjects. RA defined by ACR criteria (53). The study evaluated the effect of rheumatological treatment on periodontitis.	Clinical dental: plaque and gingival index, PPD, CAL, GCF levels of elastase, IL-1β. No dental treatment. RA subjects were treated with prednisone (88.2%), methotrexate (76.5%), NSAIDs (76.5%), and Sulfasalazine (23.5%)	Total amounts of IL-1b (p<0.01) and total elastase higher in RA+ subjects (p<0.001). Correlation between IL-1b and total elastase in the RA+ group (r=0.883; p<0.001) but not in the control group.
Mayer et al. (75)	Case–control study. RA defined by ACR criteria (53). Periodontitis defined by AAP classification (6). 10 RA (RA+) subjects, treated with with infliximab, 10 RA (RA−) untreated, 10 healthy ctr. subjects. To evaluate the influence of (TNF-α) therapy on the clinical and immunologic parameters.	Routine periodontal examintion PI, BOP, PPD, CAL, GCF samples for TNF-α (ELISA assay) RA: data: DASH 28, ESR, RA factor, or anti-CCP Ab, DMARDs use, number of erosive joints, time of RA, smoking status.	PI similar by groups. GI and BOP% higher in RA compared to RA+ and in controls. PPD and CAL less than in RA+ than in RA− and in controls TNF-α overall corr. with CAL. < GCF TNF-α in RA+ than in RA− groups. Suppression of proinflammatory cytokines may reduce periodontal inflammation.
Ribeiro et al. (76)	Case–control study. RA defined by ACR criteria (53). Periodontitis defined by AAP. Baseline to 3 months study including consecutive subjects. 16 subjects received oral hygiene instructions, supra-gingival cleaning. 26 subjects received full mouth debridement To assess the effects of non-surgical periodontal therapy on RA status.	HAQ, RF factor, ESR, drug therapy, routine periodontal assessments (PPD and CAL).	Subjects in the supra-gingival cleaning group had an increase in NSAID and prednisone compared to baseline. No correlation between periodontal parameters and RF. Trends of RF decreased in both group after periodontal intervention, ESR and HAQ improved in the subgingival debridement group, PPD and GI improved in both groups but CAL only at advanced sites in the group with subgingival debridement.
Pinho et al. (77)	Case–control study in 75 subjects over 6 months. RA defined by ACR criteria (53). To assess the effects of therapy in RA+ and RA− subjects with periodontitis.	(DAS28), CRP, ESR, RF, alpha-1 acid glycoprotein, PD (periodontal disease): ≥ 2 teeth with CAL ≥6 mm and ≥1 tooth with PPD ≥5 mm. RA+, PD+, and periodontal treatment (TX+). RA+, PD+, and no periodontal treatment (TX−). RA−, PD+, and periodontal treatment (TX+).	(RA+PD+TX+): PPD reduced (p<0.01),% plaque reduced (p<0.001). BOP reduction (p =0.07), acute phase laboratory data; NS. (RA+PD+TX−): NS changes in PD parameters; ESR was reduced (p<0.001). (RA−PD+TX+): PPD,% plaque, BOP reduced (p<0.001), systemic measures reduced (p<0.001). The relationship between RA and periodontitis activity is unclear. Periodontal treatment in the control of inflammation to avoid tooth extraction is important.
Ortiz et al. (78)	Case–control study over 6 weeks. RA defined by ACR criteria (53). 20 subjects with severe peridontitis and RA+ (10 on DMARDs and 10 on anti-TNF-α) These subjects received non-surgical periodontal treatment. 20 RA+ subjects with similar periodontal conditions (10 on DMARDs and 10 on anti-TNF-α). These subjects. did not receive periodontal treatment during the study. To assess the effect of non-surgical periodontal treatment on the signs and symptoms of RA in patients treated with or without anti-TNF-α medications.	Routine periodontal data: BOP, PI, PPD, CAL, number of teeth. RA data: VAS, ESR, DAS28, and TNF-α levels RF.	No gender effect. No changes on periodontal conditions in the two groups not receiving periodontal therapy. No difference in ESR by periodontal conditions. In both periodontal treatment groups, TNF-α decreased (p<0.001) and the number of symptomatic joints (VAS) decreased (p<0.01). Periodontal treatment groups showed sign. Decrease in BOP, PPD, and gain of attachment. Non-surgical periodontal therapy had a beneficial effect on the signs and symptoms of RA, regardless of the medications used to treat this condition. Anti-TNF-α therapy without periodontal treatment had no significant effect on the periodontal condition.
Queiroz-Junior et al. (79)	Case–control animal study of chronic Ag-induced arthritis (AIA) induced and treated with infliximab, 10 mg/kg, versus animals infected with A.a. JP2 clone (1×109 CFU). Chlorhexidine was applied in the mouth of mice every 2 d after AIA until day 14. Mice were killed at different time points (7, 14, 30, 45, and 60 days postinfection).	Morphometric evaluation of maxillae and histological examination. Knee joints of five mice per group were collected for histological evaluation. Quantification of a neutrophil enzyme marker and a macrophage enzyme marker. The concentrations of IL-1β, IL-6, IL-17, IL-10, IFN-γ, TNF-α, tumor growth factor-β, RANKL, osteoprotegerin (OPG), and anticollagen I total IgG in serum of mice were measured. Assessment of CRP.	Induction of AIA resulted in severe alveolar bone loss. Alveolar bone loss in animals with AIA was similar to that induced by oral infection with A.actinomycetemcomitans. Anti-TNF-α greatly improved AIA conditions but had no effects on the number of bacteria. Treatment with chlorhexidine improved periodontal conditions.