Impact of Periodontal Treatment on Early Rheumatoid Arthritis and the Role of 
The incidence of rheumatoid arthritis (RA) is increasing worldwide, with an estimated prevalence of approximately 0.5% . RA is characterized by chronic inflammation of the synovial membrane of the joints and progressive destruction of cartilage and erosion of marginal bone, causing clinical symptoms such as joint pain, stiffness, and disability, and is associated with systemic complications and increased mortality. Periodontal disease is a bacterial infection and inflammation affecting tooth-supporting tissues. Periodontal diseases are classified into 2 major categories. The first is gingivitis, an inflammation of the gingiva, limited to the soft-tissue areas of the gingival epithelium and connective tissue. The second is periodontitis, an inflammation of the tooth-supporting tissues that causes attachment loss and alveolar bone destruction. Severe periodontitis is one of the most serious and widespread diseases, with a global prevalence of 50% . Growing evidence suggests a close association between periodontal disease and RA . Epidemiologically, the incidence of periodontal disease in patients with RA is high, and the severity of periodontal disease is associated with RA activity, indicating a reciprocal association between periodontal disease and RA . Periodontal disease is caused by bacterial infection of periodontal tissues, whereas RA is an inflammatory arthritis associated with autoantibodies targeting modified autoepitopes. Although their etiologies differ, both are chronic inflammation diseases, resulting in the progressive destruction of connective tissue and bone due to the dysregulation of local inflammatory processes. These diseases are also affected by common genetic and environmental risk factors , suggesting that both diseases may influence each other. Recent findings have shown that periodontal disease is a potential risk factor for RA and that periodontal tissue health is important in patients with RA . Periodontal therapy for patients with RA has been shown to improve periodontal tissue health and RA disease activity [ – ]. However, most studies have examined the impact of periodontal therapy on patients with RA who have undergone treatment and with a longer disease duration. Therefore, whether the effect of periodontal therapy varies with the RA phases remains unclear. Since periodontal disease and bacteria have been suggested as possible triggers of RA , periodontal therapy might be more effective if initiated before the RA onset or in its early phase. Therefore, identifying the optimal RA phase for initiating periodontal therapy is necessary. Recently, Porphyromonas gingivalis ( P. gingivalis ) has become known to be associated with RA . P. gingivalis is a gram-negative anaerobic bacterium recognized as a keystone pathogen in the development and progression of periodontitis since it modulates the host response, causing dysbiotic microbiome and inflammation . Because P. gingivalis infection increases the serum level of IgG antibodies against this bacterium in the host and is associated with periodontal disease severity, evaluation of serum IgG antibody titers against P. gingivalis is useful in diagnosing periodontal disease . P. gingivalis can induce protein citrullination via endogenous peptidylarginine deiminase enzyme and has been implicated in the pathogenesis of RA by generating anti-citrullinated protein antibodies [ – ]. Serum IgG antibody titers against P. gingivalis are higher in patients with RA than in healthy individuals , and these titers are associated with therapeutic efficacy in RA . Therefore, serum P. gingivalis antibody titers may be associated with the efficacy of periodontal therapy in patients with RA; however, the details remain unknown. Evaluating serum P. gingivalis antibody titers may be a valuable approach for rheumatologists to confirm the requirement for periodontal disease treatment. To date, the efficacy of periodontal therapy in different RA patient populations, such as the timing of initiation of periodontal therapy and baseline serum IgG antibody titers to P. gingivalis , have not been determined. Therefore, this study aimed to evaluate the effects of treatment for periodontal disease in 30 patients with RA and the titers of antibodies to P. gingivalis . 

Ethical Statement This study was conducted in accordance with the Declaration of Helsinki and its latest amendments, and was approved by the Ethics Committee of Osaka Medical and Pharmaceutical University, Takatsuki City, Japan (approval numbers 1696 and 2817). All patients provided written informed consent before participating in the study. Participants Participants were selected from patients diagnosed with RA at the Department of Rheumatology and Collagen Disease, Osaka Medical and Pharmaceutical University Hospital, and referred to the Department of Dental and Oral Surgery. RA was defined by the presence of at least 4 of the following 7 criteria: morning stiffness, arthritis of 3 or more joint areas, symmetric arthritis, arthritis of hand joints, rheumatoid nodules, serum rheumatoid factor, and radiographical changes . Exclusion criteria included patients undergoing treatment for periodontal disease or with a history of dental visits within the past 6 months; patients with severe periodontitis, acute symptoms, or other conditions for which delayed periodontal treatment was significantly disadvantageous; and patients receiving biological disease-modifying antirheumatic drugs (bDMARDs). Study Design Participants were divided into 3 groups according to the timing of periodontal therapy initiation for RA treatment. At baseline, some patients had no history of RA treatment, while others were already undergoing RA treatment. Patients with no history of RA treatment were randomly assigned to either Group A, where periodontal therapy began concurrently with RA treatment at baseline, or Group B, where RA treatment started at baseline and periodontal therapy was initiated 3 months later. Randomization was performed by independent staff using sealed envelopes to randomly assign patients to groups A and B. Patients already receiving RA treatment at baseline were assigned to Group C, where periodontal therapy was initiated at baseline. At each time point, periodontal therapy, including oral hygiene instruction, scaling, and root planing, was performed depending on the degree of periodontal lesions. Participants’ medical records provided information on their age, sex, medical history, and medications. RA and periodontal disease status were assessed at baseline and at 3, 6, 9, and 12 months. Serum IgG antibody titers against P. gingivalis were measured at baseline. This study was registered with the UMIN Clinical Trials Registry ( www.umin.ac.jp/ctr/ ; ID: UMIN000017955). Clinical Assessment of RA To assess RA status, 2 rheumatologists examined joint tenderness and swelling in all patients. As a parameter of RA disease activity, we calculated disease activity score including 28 joints using C-reactive protein (DAS28-CRP), disease activity score including 28 joints using erythrocyte sedimentation rate (DAS28-ESR), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). RA disease activity level was classified by DAS28-CRP as remission (DAS28-CRP <2.3), low (2.3≤ DAS28-CRP ≤2.7), medium (2.7< DAS28-CRP ≤4.1), and high (DAS28-CRP >4.1.) . Ultrasonographic assessment of RA On the same day as the physical examination, patients underwent ultrasonographic (US) assessment by 2 sonographers. Twenty-eight joints (bilateral knees, shoulders, elbows, wrists, MCP joints 1–5, proximal IP joints 1–5) were examined using musculoskeletal ultrasound in grayscale (GS) and power Doppler (USPD) modes of the US diagnostic system (Viamo, Toshiba Medical Systems, Ibaraki, Japan). A semi-quantitative scoring scale (grade 0: absent; grade 1: mild; grade 2: moderate; grade 3: marked)  was used for each parameter of synovial hypertrophy by USGS and for blood flow by USPD enhancement. The total USGS and USPD scores were calculated by summing the scores for all 28 joints . Assessment of Periodontal Disease To assess periodontal status, a full-mouth clinical examination was performed by a certified dentist. Periodontal pocket depth (PPD) and bleeding on probing (BOP) were measured by using a periodontal probe ( ) at all 6 tooth sites, and the periodontal inflammatory surface area (PISA), a periodontal disease parameter that quantifies the amount of inflammation in periodontal tissue, was calculated . The severity of periodontitis was classified as no periodontitis, mild, moderate, or severe according to the Centers for Disease Control and Prevention in collaboration with the American Academy of Periodontology (CDC/AAP) periodontitis case definition . Measurement of Serum Antibody Titers to P. gingivalis Serum antibody titers against P. gingivalis were measured using chemiluminescent enzyme immunoassay with a flow-through membrane and chemiluminescent immunoautomatic analyzer (Toyobo, Osaka, Japan) with a reagent cartridge according to the manufacturer’s instructions, as previously described . The arginine gingipain (Rgp) sequence of P. gingivalis was used as the antigen . Briefly, the principle of this measurement system is based on a flow-through membrane immunoassay using 2 antigens, 1 of which is biotinylated and the other bound to alkaline phosphatase (ALP). Immune complexes formed by serum antibodies and the 2 antigens are captured on an anti-biotin antibody coated membrane in a reaction vessel, and the ALP activity is measured. The serum from patients with periodontitis in whom P. gingivalis was detected in the oral cavity was used as the positive control of analysis. The lower limit of detection for this control serum by dilution was set at 1 U/mL, and serial dilutions of this control were used to generate a calibration curve. Antibody titer levels (U/mL) were calculated using a calibration curve and the common logarithms of serum antibody titers were used for statistical analysis. Participants were divided into 3 groups – high, moderate, and low – based on quartiles of baseline serum antibody titers to P. gingivalis. Statistical Analysis Baseline characteristics of patients were evaluated using the Mann-Whitney U test or the Kruskal-Wallis test for quantitative data and the chi-square test for categorical data. RA parameters were compared between groups by Kruskal–Wallis test or Mann-Whitney U test. Changes over time from baseline (ie, within-group comparisons) were evaluated by Friedman tests or Wilcoxon signed rank test. IBM SPSS version 27 was used for statistical analysis, with a P value < 0.05 considered significant. 

This study was conducted in accordance with the Declaration of Helsinki and its latest amendments, and was approved by the Ethics Committee of Osaka Medical and Pharmaceutical University, Takatsuki City, Japan (approval numbers 1696 and 2817). All patients provided written informed consent before participating in the study. 

Participants were selected from patients diagnosed with RA at the Department of Rheumatology and Collagen Disease, Osaka Medical and Pharmaceutical University Hospital, and referred to the Department of Dental and Oral Surgery. RA was defined by the presence of at least 4 of the following 7 criteria: morning stiffness, arthritis of 3 or more joint areas, symmetric arthritis, arthritis of hand joints, rheumatoid nodules, serum rheumatoid factor, and radiographical changes . Exclusion criteria included patients undergoing treatment for periodontal disease or with a history of dental visits within the past 6 months; patients with severe periodontitis, acute symptoms, or other conditions for which delayed periodontal treatment was significantly disadvantageous; and patients receiving biological disease-modifying antirheumatic drugs (bDMARDs). 

Participants were divided into 3 groups according to the timing of periodontal therapy initiation for RA treatment. At baseline, some patients had no history of RA treatment, while others were already undergoing RA treatment. Patients with no history of RA treatment were randomly assigned to either Group A, where periodontal therapy began concurrently with RA treatment at baseline, or Group B, where RA treatment started at baseline and periodontal therapy was initiated 3 months later. Randomization was performed by independent staff using sealed envelopes to randomly assign patients to groups A and B. Patients already receiving RA treatment at baseline were assigned to Group C, where periodontal therapy was initiated at baseline. At each time point, periodontal therapy, including oral hygiene instruction, scaling, and root planing, was performed depending on the degree of periodontal lesions. Participants’ medical records provided information on their age, sex, medical history, and medications. RA and periodontal disease status were assessed at baseline and at 3, 6, 9, and 12 months. Serum IgG antibody titers against P. gingivalis were measured at baseline. This study was registered with the UMIN Clinical Trials Registry ( www.umin.ac.jp/ctr/ ; ID: UMIN000017955). 

To assess RA status, 2 rheumatologists examined joint tenderness and swelling in all patients. As a parameter of RA disease activity, we calculated disease activity score including 28 joints using C-reactive protein (DAS28-CRP), disease activity score including 28 joints using erythrocyte sedimentation rate (DAS28-ESR), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). RA disease activity level was classified by DAS28-CRP as remission (DAS28-CRP <2.3), low (2.3≤ DAS28-CRP ≤2.7), medium (2.7< DAS28-CRP ≤4.1), and high (DAS28-CRP >4.1.) . 

On the same day as the physical examination, patients underwent ultrasonographic (US) assessment by 2 sonographers. Twenty-eight joints (bilateral knees, shoulders, elbows, wrists, MCP joints 1–5, proximal IP joints 1–5) were examined using musculoskeletal ultrasound in grayscale (GS) and power Doppler (USPD) modes of the US diagnostic system (Viamo, Toshiba Medical Systems, Ibaraki, Japan). A semi-quantitative scoring scale (grade 0: absent; grade 1: mild; grade 2: moderate; grade 3: marked)  was used for each parameter of synovial hypertrophy by USGS and for blood flow by USPD enhancement. The total USGS and USPD scores were calculated by summing the scores for all 28 joints . 

To assess periodontal status, a full-mouth clinical examination was performed by a certified dentist. Periodontal pocket depth (PPD) and bleeding on probing (BOP) were measured by using a periodontal probe ( ) at all 6 tooth sites, and the periodontal inflammatory surface area (PISA), a periodontal disease parameter that quantifies the amount of inflammation in periodontal tissue, was calculated . The severity of periodontitis was classified as no periodontitis, mild, moderate, or severe according to the Centers for Disease Control and Prevention in collaboration with the American Academy of Periodontology (CDC/AAP) periodontitis case definition . 

P. gingivalis Serum antibody titers against P. gingivalis were measured using chemiluminescent enzyme immunoassay with a flow-through membrane and chemiluminescent immunoautomatic analyzer (Toyobo, Osaka, Japan) with a reagent cartridge according to the manufacturer’s instructions, as previously described . The arginine gingipain (Rgp) sequence of P. gingivalis was used as the antigen . Briefly, the principle of this measurement system is based on a flow-through membrane immunoassay using 2 antigens, 1 of which is biotinylated and the other bound to alkaline phosphatase (ALP). Immune complexes formed by serum antibodies and the 2 antigens are captured on an anti-biotin antibody coated membrane in a reaction vessel, and the ALP activity is measured. The serum from patients with periodontitis in whom P. gingivalis was detected in the oral cavity was used as the positive control of analysis. The lower limit of detection for this control serum by dilution was set at 1 U/mL, and serial dilutions of this control were used to generate a calibration curve. Antibody titer levels (U/mL) were calculated using a calibration curve and the common logarithms of serum antibody titers were used for statistical analysis. Participants were divided into 3 groups – high, moderate, and low – based on quartiles of baseline serum antibody titers to P. gingivalis. 

Baseline characteristics of patients were evaluated using the Mann-Whitney U test or the Kruskal-Wallis test for quantitative data and the chi-square test for categorical data. RA parameters were compared between groups by Kruskal–Wallis test or Mann-Whitney U test. Changes over time from baseline (ie, within-group comparisons) were evaluated by Friedman tests or Wilcoxon signed rank test. IBM SPSS version 27 was used for statistical analysis, with a P value < 0.05 considered significant. 

Participants A flowchart of the study participants, including reasons for exclusion, is shown in . Of the 43 individuals assessed for eligibility, 34 were eligible for inclusion. Nineteen patients without prior RA treatment were randomly assigned to Group A (n=9), where periodontal therapy began simultaneously with RA treatment, or Group B (n=10), where periodontal therapy was performed 3 months after initiating RA treatment. Among the 15 patients who had already undergone RA treatment, 4 were excluded because of loss to follow-up, and 11 started periodontal therapy at baseline (Group C). Baseline Characteristics The baseline characteristics of the participants in each group at different initiation timing of periodontal therapy are shown in . Age, sex, oral condition, and serum P. gingivalis antibody titers did not differ significantly across groups. The degree of periodontal disease in the patients in each group ranged from mild to severe periodontitis, with no significant differences between the groups. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were used in all patients in Group C at baseline and in all patients in Groups A, B, and C at the 12-month observation period. Differences in the Effects of Periodontal Therapy by Initiation Timing At baseline, no differences in RA activity were observed between Groups A and B. Patients in Groups A and B, which started RA treatment at baseline, showed significant improvements in DAS28-CRP, SDAI, and CDAI scores after 3 months of RA treatment compared to baseline ( P <0.05). After 3 months, DAS-ESR improved in Group A, but not in Group B. Ultrasound results showed improvement in USPD after 6 months in Group B and after 12 months in Group A ( P <0.05, ). Group A, which started periodontal therapy simultaneously with RA treatment, showed no difference in the RA index at any time point compared to Group B, which started periodontal therapy 3 months after RA treatment ( ). However, the improvement in RA activity, measured by DAS28-CRP, from baseline to 3 months was greater in Group A than in Group B ( P <0.05, ), although subsequent changes were similar between both groups. After 3 months, 77.8% in Group A had RA activity levels in remission based on DAS28-CRP, compared to 30.0% in Group B ( ). Furthermore, we compared Groups A and C, where periodontal therapy was initiated at baseline. Group C, which had previously started RA treatment at baseline, showed no significant difference in RA indices at any time point, and no differences in the RA index were observed at any time point in Group A compared with Group C ( ). The improvement in RA activity by DAS28-CRP from baseline to 3 months was greater in Group A than in Group C ( P <0.01, ). The number of patients at each disease activity level based on DAS28-CRP at each time point did not differ significantly between Groups A and C ( ). These results suggest that patients who start periodontal therapy at an early stage of RA treatment have the potential for early improvements in RA activity. Differences in the Effects of Periodontal Therapy Based on the Titers of Antibodies to P. gingivalis Since no significant differences in RA activity were observed after 12 months among Groups A, B, and C ( , ), participants were divided into 3 groups based on quartiles of baseline serum IgG antibody titers against P. gingivalis : high (H), medium (M), and low (L) groups. RA activity after 12 months of RA treatment with periodontal therapy was then compared among these groups. P. gingivalis antibody titers at baseline were significantly different in each group ( ). At baseline, the number of teeth bleeding at probing and the degree of periodontal disease differed significantly between groups ( P <0.05, ). While RA activity by DAS28-CRP was not significantly different between the groups at baseline ( ), Group L had higher DAS28-CRP than group M after 12 months of treatment ( P <0.05, ), with no significant differences in other indices. After 12 months, the RA activity level measured by DAS28-CRP was in remission in 37.5%, 76.9%, and 75.0% of the patients in Groups L, M, and H, respectively ( ). The change in the proportion of patients per RA activity level from baseline to 12 months was not seen in Group L, but improved in Groups M and H ( ). These results suggest that RA treatment with periodontal therapy may be more effective in improving RA activity in patients with higher baseline serum IgG antibody titers against P. gingivalis than in those with lower titers. 

A flowchart of the study participants, including reasons for exclusion, is shown in . Of the 43 individuals assessed for eligibility, 34 were eligible for inclusion. Nineteen patients without prior RA treatment were randomly assigned to Group A (n=9), where periodontal therapy began simultaneously with RA treatment, or Group B (n=10), where periodontal therapy was performed 3 months after initiating RA treatment. Among the 15 patients who had already undergone RA treatment, 4 were excluded because of loss to follow-up, and 11 started periodontal therapy at baseline (Group C). 

The baseline characteristics of the participants in each group at different initiation timing of periodontal therapy are shown in . Age, sex, oral condition, and serum P. gingivalis antibody titers did not differ significantly across groups. The degree of periodontal disease in the patients in each group ranged from mild to severe periodontitis, with no significant differences between the groups. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were used in all patients in Group C at baseline and in all patients in Groups A, B, and C at the 12-month observation period. 

At baseline, no differences in RA activity were observed between Groups A and B. Patients in Groups A and B, which started RA treatment at baseline, showed significant improvements in DAS28-CRP, SDAI, and CDAI scores after 3 months of RA treatment compared to baseline ( P <0.05). After 3 months, DAS-ESR improved in Group A, but not in Group B. Ultrasound results showed improvement in USPD after 6 months in Group B and after 12 months in Group A ( P <0.05, ). Group A, which started periodontal therapy simultaneously with RA treatment, showed no difference in the RA index at any time point compared to Group B, which started periodontal therapy 3 months after RA treatment ( ). However, the improvement in RA activity, measured by DAS28-CRP, from baseline to 3 months was greater in Group A than in Group B ( P <0.05, ), although subsequent changes were similar between both groups. After 3 months, 77.8% in Group A had RA activity levels in remission based on DAS28-CRP, compared to 30.0% in Group B ( ). Furthermore, we compared Groups A and C, where periodontal therapy was initiated at baseline. Group C, which had previously started RA treatment at baseline, showed no significant difference in RA indices at any time point, and no differences in the RA index were observed at any time point in Group A compared with Group C ( ). The improvement in RA activity by DAS28-CRP from baseline to 3 months was greater in Group A than in Group C ( P <0.01, ). The number of patients at each disease activity level based on DAS28-CRP at each time point did not differ significantly between Groups A and C ( ). These results suggest that patients who start periodontal therapy at an early stage of RA treatment have the potential for early improvements in RA activity. 

P. gingivalis Since no significant differences in RA activity were observed after 12 months among Groups A, B, and C ( , ), participants were divided into 3 groups based on quartiles of baseline serum IgG antibody titers against P. gingivalis : high (H), medium (M), and low (L) groups. RA activity after 12 months of RA treatment with periodontal therapy was then compared among these groups. P. gingivalis antibody titers at baseline were significantly different in each group ( ). At baseline, the number of teeth bleeding at probing and the degree of periodontal disease differed significantly between groups ( P <0.05, ). While RA activity by DAS28-CRP was not significantly different between the groups at baseline ( ), Group L had higher DAS28-CRP than group M after 12 months of treatment ( P <0.05, ), with no significant differences in other indices. After 12 months, the RA activity level measured by DAS28-CRP was in remission in 37.5%, 76.9%, and 75.0% of the patients in Groups L, M, and H, respectively ( ). The change in the proportion of patients per RA activity level from baseline to 12 months was not seen in Group L, but improved in Groups M and H ( ). These results suggest that RA treatment with periodontal therapy may be more effective in improving RA activity in patients with higher baseline serum IgG antibody titers against P. gingivalis than in those with lower titers. 

In this study, periodontal therapy was administered alongside RA treatment, and its effects were compared across groups with different initiation times of periodontal therapy and groups with different serum P. gingivalis antibody titers. RA activity improved earlier in patients who started periodontal therapy simultaneously with RA treatment than in those who started periodontal therapy after RA treatment. Additionally, after 1 year of RA treatment with periodontal therapy, RA activity improved in patients with higher serum P. gingivalis antibody titers than in those with lower titers. These findings indicate that periodontal therapy for RA is more effective in patients with early-stage disease and high serum P. gingivalis antibody titers. Periodontal therapy has been reported to improve RA activity . In this study, when periodontal therapy was initiated simultaneously with RA treatment in untreated RA patients, there was a greater improvement in RA activity based on DAS28-CRP at 3 months compared with no periodontal therapy. In addition, RA-untreated patients had a greater improvement in RA activity 3 months after the start of periodontal therapy than did patients who had already started RA treatment (duration of treatment: 5 months to 7 years).These results are consistent with those of several previous studies that reported short-term improvements in DAS28 with periodontal treatment in patients with RA [ , , ]. However, previous reports did not consider the duration of RA treatment or the duration of RA treatment in years . A novel finding of this study is that starting periodontal therapy alongside RA treatment at diagnosis may benefit early RA remission. Additionally, there was no difference in RA disease activity at 1-year observation between untreated and treated RA patients in groups that started periodontal therapy at different times. Few related studies have reported follow-up data of up to 1 year, confirming the findings reported for the short-term effect of periodontal therapy in RA treatment. Randomized trials, such as the present study, comparing immediate and delayed periodontal therapy in patients with RA have been reported as pilot studies . Therefore, further large-scale studies focusing on the timing of periodontal therapy initiation are needed. The observed improvement in RA activity is likely due to periodontal therapy suppressing periodontal infection and inflammation . However, in this study, periodontal treatment did not significantly improve periodontal status. This may be due to the inclusion of individuals with mild or no periodontal disease, as patients were not selected based on periodontal disease severity. Despite this, it is noteworthy that periodontal therapy was effective in improving RA activity. In this study, the improvement in RA activity after 1 year of RA treatment with periodontal therapy was significantly greater in patients with higher baseline serum IgG antibody titers against P. gingivalis than in those with lower titers. Previous reports have demonstrated that serum P. gingivalis antibody titers are associated with therapeutic efficacy in RA [ , , ]. These studies suggest that a lower baseline P. gingivalis IgG response in patients with RA is associated with a better clinical response to RA treatment. Therefore, the finding that patients with RA and low baseline serum P. gingivalis titer are less responsive to RA treatment when periodontal therapy is conducted alongside RA treatment suggests the potential value of periodontal therapy in patients with high serum P. gingivalis antibody titers. Selecting patients for periodontal therapy in RA treatment based on P. gingivalis antibody titers may be beneficial. The importance of periodontal therapy for individuals at risk of RA is not well understood by these individuals or the health professionals involved in their care . Conducting oral examinations in clinical settings where RA treatment is administered is challenging. However, it is easy to evaluate serum P. gingivalis antibody titers in patients with RA because they are under continuous management with periodic blood sampling. Therefore, evaluating serum P. gingivalis antibody titers is expected to be a simple and effective means of screening individuals for whom periodontal intervention is effective in RA treatment. For this purpose, clinical studies with larger numbers of patients are required. This study has a few limitations. First, owing to the nature of this interventional study, the sample size was small. The sample size of 30 patients was determined based on clinical judgment and practical considerations, not formal statistical inference. Second, as this was a randomized controlled trial, baseline periodontal status and RA treatment were not perfectly matched. Third, although patients treated with bDMARDs at baseline were initially excluded, some participants changed their medication regimen during the 1-year follow-up period, including bDMARDs, and were not excluded afterward. Recently, RA medications have been shown to affect periodontal health , which may be an important factor in evaluating the efficacy of periodontal therapy in RA treatment. Among RA drugs, the efficacy of bDMARD is associated with periodontal disease; that is, RA patients with a low severity of periodontal disease have a better clinical response to bDMARD therapy . Therefore, the results of this study may have been influenced by the differences in RA treatment, and future studies should be conducted to eliminate this influence. This was a preliminary pilot project with a limited sample size, necessitating a more extensive, well-controlled study to confirm and thoroughly examine our findings. 

Treatment for periodontal disease in patients with RA is more effective in patients with early-phase RA and higher serum P. gingivalis antibody titers. Therefore, early periodontal therapy in patients with RA and high serum P. gingivalis antibody titers may enhance RA treatment outcomes. 

