Effect Assessment of Periodontal Prophylaxis on Rheumatoid Arthritis Activity.
Condition: Anti-CCP Positive Early Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Observational

Summary: 
      The purpose of this study is to assess the impact of an intervention (scaled every 06 months
      associated with the use of mouthwash with essential oils (toothpaste and Listerine® 2 times /
      day containing polymer Triclosan (Colgate Total®)) on the activity of rheumatoid arthritis
    

Detailed description: 
      Introduction: Several epidemiological studies have suggested that a link between periodontal
      disease and rheumatoid arthritis. In cohorts, the risk of development of rheumatoid arthritis
      is increased in subjects with periodontal disease. The main bacterium implicated in chronic
      periodontal disease is Porphyromas gingivalis, a commensal microorganism of the mouth. P.
      gingivalis is the only microorganism with a deiminase capable of transforming arginine into
      citrulline, and is suspected of to play a major role in the production of anti-citrulline
      antibodies, the principal diagnostic marker of rheumatoid arthritis.

      Hypotheses: The regular professional and individual plaque control in patients with
      rheumatoid arthritis (standard of care) - i.e. decreasing oral bacterial load, including P.
      gingivalis - reduces the activity of rheumatoid arthritis Principal objective: To assess the
      impact of professional periodontal scaling every 6 months combined with the individual plaque
      control, i.e. toothbrushing plus the use of mouthrinses on rheumatoid arthritis activity.

      Methodology: The trial design is innovative and based on random selection of a sample of
      patients in an observational cohort of patients as described in the recent publication
      "Cohort Multiple Randomised Controlled Trials Design" (Ref.: BMJ 2010; 340: c1066). A
      randomly selected sample of eligible patients from the cohort will be asked to take part in
      the study. Changes in the randomised sample will be compared to those of other potentially
      eligible patients from the cohort. The cohort used will be the ESPOIR cohort, a cohort
      including 813 patients who initially presented with early undifferentiated polyarthritis that
      developed into rheumatoid arthritis with anti-citrulline antibodies in approximately 40 to
      50% of cases.

      Procedures studied: Periodontal scaling every 6 months and twice daily use of a mouthwash
      containing essential oils (Listerine®) plus a triclosan/copolymer toothpaste (Colgate
      Total®).

      Sample size calculation: The principal assessment criterion is DAS variations at 1 year. The
      expected statistical power is 80% (the type I risk being set at 5%) and the standard
      deviation common to the two samples for DAS variation is evaluated at 1.5. With these
      hypotheses, the inclusion of 100 patients in the study group and 100 patients in the control
      group will produce an effect size of 0.40 (i.e. a difference in DAS between the two groups
      equal to 0.6).

      Statistical analysis: A linear, mixed-effects model will be used to compare DAS variations
      between the two groups. In addition, the Mixed Model for Repeated Measurements (MMRM) based
      on a linear mixed model will include two other random effects, i.e.: the centre effect and
      the centre*treatment interaction effect, which will be used to measure heterogeneity between
      the centres and heterogeneity of the effect of the procedure. Finally, propensity scores with
      adjustment by weighting will be used to take into account any potential imbalances between
      the two study arms.
    

Intervention name(s): Periodontal prophylaxis
Intervention type(s): Other
Intervention description(s): Periodontal scaling (every 6 months) plus mouthrinses plus toothbrushing (twice daily). Removal of adherent plaque and calculus with ultrasonic instruments and hand instruments, such as periodontal scalers and curettes, and polishing of the teeth
Other intervention name(s): Mouthrinse: Listerine®; toothpaste: Colgate Total®
Intervention MeSH terms: Listerine
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Population selected from the ESPOIR early arthritis Cohort
      
Biospecimen description: 
      Biospecimen: gingival fluid

      A first sampling will take place at T0 and the second at Month 12 (test end).

      A bacterial sampling at 4 deepest periodontal pockets will be carried. It will quantify the 9
      following bacteria:

      Aggregatibacter actinomycetemcomitans Porphyromonas gingivalis Prevotella intermedia
      Tannerella forsythensis Treponema denticola Peptostreptococcus micros Fusobacterium nucleatum
      Eikenella corrodens Campylobacter rectus
    
Keywords: Rheumatoid arthritis; P.gingivalis; Periodontal disease; Plaque control; Prophylaxis; Oral hygiene instruction