Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial.

OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308.

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial.

Importance: Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective: To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions: Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures: The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results: Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance: Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01881308.

First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach.

OBJECTIVES: To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). METHODS: Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naïve early RA or established RA starting/switching biologics. An extensive US examination was performed by experienced sonographers using a validated grey-scale (GSUS) and power Doppler (PDUS) semiquantitative scoring system with scores 0-3 for both GSUS and PDUS in 36 joints and four tendons. We performed factor analysis in the early RA US data and selected candidate joint/tendon sets based on these results. The proportion of information in the total US scores retained in these candidate sets was assessed by R(2) from linear regression analysis. Finally, the candidate sets and previously proposed joint scores were tested in the established RA cohort, and we also evaluated the sensitivity to change with standardised response means. RESULTS: 227 patients with early RA and 212 patients with established RA were included. We identified two candidate sets of joints/tendons: candidate set A consisted of seven joints/two tendons (meatacarpophalangeal 1 (MCP1), MCP2, proximal interphalangeal 3, radiocarpal, elbow, metatarsophalangeal 1 (MTP1), MTP2, tibialis posterior tendon, extensor carpi ulnaris tendon) and set B of nine joints/two tendons (MCP5 and MTP5 added to set A). Unilateral reduced scores retained 78%-85% of the information in total score, while bilateral reduced scores retained 89%-93%, and both sets performed better than previously proposed reduced joint scores, and similar or slightly better regarding sensitivity to change. CONCLUSIONS: The reduced GSUS and PDUS scores retained most of the information from the total score and performed well in a validation cohort of established RA. TRIAL REGISTATION NUMBER: NCT01205854, ACTRN12610000284066.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. METHODS: In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. FINDINGS: Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). INTERPRETATION: Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. FUNDING: Research Council of Norway and South-Eastern Norway Regional Health Authority.

VEXAS Syndrome in a Patient with Myeloproliferative Neoplasia.

VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a JAK2V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the UBA1 gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the DNMT3 too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in JAK2 mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial.

OBJECTIVE:  To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. DESIGN:  Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. SETTING:  Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. PARTICIPANTS:  238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. INTERVENTIONS:  122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. MAIN OUTCOME MEASURES:  The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. RESULTS:  26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval -7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. CONCLUSIONS:  The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology.Trial registration Clinical trials NCT01205854.

Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach.

OBJECTIVE: To develop and validate a responsive and feasible ultrasound inflammation score for rheumatoid arthritis (RA). METHODS: We used data from cohorts of early RA (development) and established RA starting/switching biologic therapy (validation). 4 tendons and 36 joints were examined by a grey scale (GSUS) and power Doppler semiquantitative ultrasound (PDUS) scoring system (full score). Ultrasound score components were selected based on factor analyses of 3-month change in the development cohort. Responsiveness was assessed by standardised response means (SRMs). We assessed the proportion of information retained from the full score by linear regression. RESULTS: 118 patients with early and 212 patients with established RA were included. The final ultrasound score included 8 joints (metacarpophalangeal 1-2-3, proximal interphalangeal 2-3, radiocarpal, metatarsophalangeal 2-3) and 1 tendon (extensor carpi ulnaris) examined bilaterally. The 6-month SRMs for the final score were -1.24 (95% CI -1.47 to -1.02) for GSUS, and -1.09 (-1.25 to -0.92) for PDUS in early RA, with 87% of total information retained for GSUS and 90% for PDUS. The new score performed somewhat better than formerly proposed scores in the validation cohort. CONCLUSIONS: The Ultrasound in Rheumatoid Arthritis 9 joint/tendon score (USRA9) inflammation score showed good responsiveness, retained most of the information from the original full score and overall performed better than previous scores in a validation cohort. TRIAL REGISTRATION NUMBERS: NCT01205854, ACTRN12610000284066; Post-results.

A randomized double blind comparison of short-term duodenally administrated whale and seal blubber oils in patients with inflammatory bowel disease and joint pain.

Compared with soy oil, 10 days treatment with seal oil (SO), 10mLx3 daily, self-administrated through a nasoduodenal feeding tube, relieves joint pain in patients with inflammatory bowel disease (IBD). This randomized, controlled, double blind pilot trial compares SO and whale oil (WO) administered similarly by duodenal tube, for 10 days in 18 patients with IBD-related joint pain (n=9 per group). Other long chain n-3 polyunsaturated fatty acids were prohibited 7-days prior to and during study. Significant changes from baseline to study end were observed in both groups: reduced plasma arachidonic acid to eicosapentaenoic acid ratio and prostaglandin E(2) (PGE(2)) levels (tendency in WO group), decreased IBD-related joint pain and IBD-disease activity, and improved quality of life. These changes were not significantly different between SO and WO groups. Inhibition of cyclooxygenase is consistent with amelioration of IBD-related joint pain, but, as active control was used, effects need confirmation.

S100 proteins calprotectin and S100A12 are related to radiographic changes rather than disease activity in psoriatic arthritis with low disease activity.

OBJECTIVE: To investigate serum levels of calprotectin (S100A8/S100A9) and S100A12 as markers of disease activity or distinct clinical or radiographic features in patients with psoriatic arthritis (PsA). METHODS: Serum levels of calprotectin and S100A12, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined in 119 patients with PsA. Correlations to clinical variables were calculated, and subgroups of patients were compared. RESULTS: The correlations to clinical disease activity measures were stronger for CRP than for ESR and calprotectin. In the regression analysis, calprotectin was identified as an independently associated factor for presence of peripheral radiographic features of arthritis (OR 1.33, 95% CI 1.01-1.76). S100A12 levels were also elevated in those with peripheral radiographic features (p = 0.036), but did not correlate with clinical variables of disease activity. CONCLUSION: Calprotectin and S100A12 do not perform better than traditional biomarkers of disease activity in PsA, but were associated with presence of peripheral radiographic features in this cross-sectional study. The patients' low level of disease activity may have led to underestimation of the associations between any biomarker and disease measures.

Subjective improvement in patients with psoriatic arthritis after short-term oral treatment with seal oil. A pilot study with double blind comparison to soy oil.

OBJECTIVE: To investigate effects of short-term oral treatment with seal oil in patients with psoriatic arthritis (PsA). METHODS: Forty-three patients with polyarticular PsA were randomized to receive oral treatment for 2 weeks with either seal oil or soy oil in a double blind controlled trial. Clinical and biochemical variables were assessed at baseline, after treatment, and 4 weeks post-treatment. Patients were allowed to continue nonsteroidal antiinflammatory drugs (NSAID) and disease modifying antirheumatic drugs (DMARD) during the study. RESULTS: Forty patients completed the study, 20 in each treatment group. Patients in the seal oil group reported a significant improvement in global assessment of the disease 4 weeks post- treatment (p < 0.01), and both groups showed a trend toward improvement in tender joint count, but the differences between the groups were not significant. There was a fall in the ratio of n-6 to n-3 fatty acids and in arachidonic acid (AA) to eicosapentaenoic acid (EPA) in serum after treatment with seal oil (p < 0.01). Twenty-one percent of all patients had elevated values of calprotectin in feces suggestive of asymptomatic colitis. CONCLUSION: Treatment with seal oil was followed by a modest improvement in patient's global assessment of the disease and a trend towards a decrease in number of tender joints. There was a shift in fatty acid composition in serum toward a putative antiinflammatory profile. Oral treatment with seal oil may have NSAID-like effects in PsA.

Prevalence, disease manifestations, and treatment of psoriatic arthritis in Western Norway.

OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA) in a geographically defined population, and to characterize the clinical manifestations and medical treatment for PsA. METHODS: Prevalent cases were identified for the years 1999-2002 at the rheumatology centers for the population of 442,000 inhabitants. Clinical data were extracted from patient records. Cases with psoriasis and peripheral arthritis and/or radiographic evidence of spondyloarthritis were considered to have PsA, those with other arthritides were excluded. RESULTS: In total, 634 patients with PsA were identified from the adult population, equivalent to a prevalence of 1.95 per 1000 (1.80-2.10). There were no significant sex differences in rates; for both sexes the prevalence was highest in the age group 40 to 59 years. Polyarthritis was the most frequent subclass (68.6%). Oligoarthritis, monoarthritis, and arthritis confined to the spine or sacroiliac joints were seen in 22.9%, 5.8%, and 2.7% of cases, respectively. Mean age was higher (50.6 yrs for all cases), and mean disease duration was longer (10.7 yrs) with increasing number of joints affected. The mean erythrocyte sedimentation rate and C-reactive protein were higher with increasing number of joints affected and disease duration. Intraarticular injection of glucocorticoids had been administered to 40.0% of the patients during the last year. Disease modifying antirheumatic drugs were used by 40.0%, with oral methotrexate being the most frequently used. CONCLUSION: The estimated prevalence of PsA was 1.95 per 1000 adult inhabitants, which is higher than previously reported. The demographic data support the presence of a shift from mono- and oligoarthritis to polyarthritis and increased inflammatory activity with increasing disease duration. Methotrexate and intraarticular glucocorticoids were frequently used treatments.

A prospective study of sicca symptoms in patients with rheumatoid arthritis.

OBJECTIVE: To investigate sicca symptoms in patients with rheumatoid arthritis (RA) with respect to constancy, temporal changes of prevalence, and possible risk factors. METHODS: A prospective cohort study of 70 patients with RA was conducted over 5 years. The main variables of interest were the 6 questions on sicca symptoms used in the preliminary European criteria for Sjögren's syndrome. RESULTS: Fourteen patients were lost to followup. We found that 84.2% (95% confidence interval [95% CI] 59.5-95.8) of the patients reporting sicca symptoms at baseline also reported them at followup. During the study period, sicca symptoms increased by 52.6% in general (P = 0.02) and by 80.0% for the ocular components (P = 0.04). Sicca symptoms (odds ratio [OR] = 8.35, 95% CI 1.91-36.49) and pain (OR = 1.03, 95% CI 1.00-1.07) at baseline were identified as independent predictive factors for sicca symptoms at followup. CONCLUSIONS: Sicca symptoms in patients with RA are remarkably constant over time. There is also a substantial time-dependent increase in the prevalence of such symptoms. As the prevalence of ocular sicca symptoms in general populations tend to level out with age, there seems to be a disease-related increase of ocular symptoms over time in patients with RA. Present pain and sicca symptoms constitute risk factors for future sicca symptoms.

Leukocyte protein calprotectin and outcome in rheumatoid arthritis. A longitudinal study.

OBJECTIVE: To determine if calprotectin is predictive for outcome in patients with rheumatoid arthritis (RA). METHODS: Fifty six RA in-patients with variable disease duration were prospectively followed for five years. Clinical and laboratory data were collected to assess disease activity. Health Assessment Questionnaire (HAQ) and radiographic scores (of hands and wrists) as described by Larsen were used as outcome measures. Plasma calprotectin levels were determined with ELISA technique. RESULTS: Significant correlations (r) were found cross-sectionally at follow-up between calprotectin concentration and other known parameters of disease activity and severity: CRP (r = 0.67). investigator's global assessment of disease activity (r = 0.57). Waaler titre (r = 0.50). HAQ score (r = 0.48) and number of swollen joints (r = 0.48). Calprotectin at baseline was not identified as an independent predictor for HAQ or radiographic progression in the multivariate analysis. CONCLUSION: The results confirm calprotectin as a good measure of disease activity and joint inflammation in RA. However, the level of calprotectin at baseline was not predictive for radiographic damage or functional impairment five years later.

Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients.

The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases.