Effect of periodontal treatment on the clinical parameters of patients with rheumatoid arthritis: study protocol of the randomized, controlled ESPERA trial

Paul Monsarrat 0 Jean-Nol Vergnes 0 Alain Cantagrel 2 Nadge Algans 1 Sarah Cousty 0 Philippe Kmoun 0 Caroline Bertrand 4 5 Elise Arriv 4 5 Christophe Bou 4 5 Cyril Sdarat 4 5 Thierry Schaeverbeke 3 Cathy Nabet 0 Michel Sixou 0 0 Department of Dentistry, Toulouse University Hospital (CHU de Toulouse) and Toulouse Dental School, Paul Sabatier University , Toulouse , France 1 Clinical Research and Innovation Department (DRCI), Toulouse University Hospital (CHU de Toulouse) , Toulouse , France 2 Department of Rheumatology, Toulouse University Hospital (CHU de Toulouse) , Toulouse , France 3 Department of Rheumatology, Bordeaux University Hospital, Bordeaux 2 University , Bordeaux , France 4 Department of Odontology, Bordeaux 2 University , Bordeaux , France 5 Department of Dentistry and Oral health, Bordeaux University Hospital , Bordeaux , France Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder that leads to joint damage, deformity, and pain. It affects approximately 1% of adults in developed countries. Periodontitis is a chronic oral infection, caused by inflammatory reactions to gram-negative anaerobic bacteria, and affecting about 35 to 50% of adults. If left untreated, periodontitis can lead to tooth loss. A significant association has been shown to exist between periodontitis and RA in observational studies. Some intervention studies have suggested that periodontal treatment can reduce serum inflammatory biomarkers such as C-reactive protein, or erythrocyte sedimentation rate. We hypothesize that periodontitis could be an aggravating factor in patients with RA, and that its treatment would improve RA outcomes. The aim of this clinical trial is to assess the effect of periodontal treatment on the biological and clinical parameters of patients with RA. Methods/design: The ESPERA (Experimental Study of Periodontitis and Rheumatoid Arthritis) study is an open-label, randomized, controlled trial. Subjects with both RA and periodontitis will be recruited at two university hospitals in southwestern France. In total, 40 subjects will be randomized into two arms (intervention and control groups), and will be followed up for 3 months. Intervention will consist of full-mouth supra-gingival and sub-gingival non-surgical scaling and root planing, followed by systemic antibiotic therapy, local antiseptics, and oral hygiene instructions. After the 3-month follow-up period, the same intervention will be applied to the subjects randomized to the control group. The primary outcome will be change of in Disease Activity Score in 28 Joints (DAS28) at the end of the follow-up period. Secondary outcomes will be the percentages of subjects with 20%, 50%, and 70% improvement in disease according to the American College of Rheumatology criteria. Health-related quality of life assessments (the Health Assessment Questionnaire and the Geriatric Oral Health Assessment Index) will also be compared between the two groups. (Continued on next page) - (Continued from previous page) Discussion: Evidence-based management of potential aggravating factors in subjects with active RA could be of clinical importance, yet there are few randomized controlled trials on the effect of periodontal treatment on the clinical parameters of RA. The ESPERA trial is designed to determine if non-surgical periodontal treatment could improve clinical outcomes in patients with active RA, and the quality of life of these patients. Trial registration: The ESPERA Trial was registered in Current Controlled Trials [ISRCTN79186420] on 2012/03/20. The trial started recruiting on 2012/03/06. Background Rheumatoid arthritis (RA) is a chronic and destructive systemic autoimmune disease, characterized by the accumulation and persistence of inflammatory infiltrates in the synovial membrane, and the inflammatory condition of joints, tendons, and periarticular structures [1,2]. If untreated, the inflammatory condition can lead to destruction of the bone and cartilage of joints, and also of ligaments and soft tissues, causing severe disability, clinically important impact on quality of life (QOL), and substantial effects in terms of cost and productivity loss [3]. RA affects approximately 0.3% of patients in France [4], with a usual female:male sex ratio of 3:1 [5]. Periodontal diseases are diseases that affect the tissues supporting the teeth. The first step in the gum-disease process is gingivitis, an immune-inflammatory response to the bacterial colonization of tooth surfaces, without bone loss. Gingivitis can progress into periodontitis, an advanced and more serious stage of gum disease, which includes alveolar bone loss, eventually leading to tooth loss [6]. Periodontitis is a chronic oral infection caused by inflammatory reactions to gram-negative anaerobic bacteria, and affecting about 35 to 50% of adults [7,8]. Several recent research studies have shown that periodontitis could have an important influence on systemic inflammatory loading, and could trigger or worsen many medical conditions, including myocardial infarction and stroke [9,10], unbalanced glycemic control in patients with diabetis [11,12], preterm births [13,14], occurrence of chronic obstructive pulmonary disease and respiratory complications [15], or even erectile dysfunction [16]. RA and periodontitis share some pathogenic features; both are chronic inflammatory diseases with genetic and environmental influences and immunoregulatory imbalance, and both lead to destruction of conjunctive and hard tissues [17,18]. A study has reported that the frequency of RA is significantly higher in patients with periodontal disease than in subjects without periodontitis (3.95% versus 0.66%) [17]. Other studies have reported a higher incidence of missing teeth, dental plaque, greater periodontal pocket depth, or worse clinical attachment levels in patients with RA [18-20]. On the one hand, it is likely that patients with RA may encounter more difficulties in achieving good oral health because of joint pain or functional limitation [20,21], while on the other hand, it is hypothesized that periodontitis could be a risk factor or an aggravating factor for RA. In particular, the role of Porphyromonas gingivalis, a well-known periodontopathogenic bacterium, has been widely highlighted, because this oral bacterium has an endogenous peptidylarginine deiminase enzyme [22]. This enzyme is responsible for citrullination of arginine residuals, which is one of the crucial first steps in the development of RA [23-25]. A few studies have shown that periodontal treatment might induce a significant decrease in erythrocyte sedimentation rate (ESR) or Disease Activity Scores in 28 joints (DAS28) [26-29]. Further prospective studies, especially randomized controlled trials, are needed to determine whether full management of periodontitis in patients with RA results in improved clinical or QOL outcomes. The aim of this study is to assess the effect of periodontal tre (...truncated)