Full Mouth Disinfection and Antibiotics for Periodontitis in High or Moderate Disease Activity Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a currently incurable disease of unknown origin characterized by joint inflammation and the breakdown of immune tolerance to a variety of antigens, including citrullinated peptides generated by peptidyl-arginine-deiminases (PAD's). Porphyromonas gingivalis (P. g.) derived PAD enzyme (PPAD) citrullinates preferentially C-terminal arginine residues, which may be generated by P.g. derived gingipain protein (Rgpb) cleavage, but several of the originated peptide sequences from enolase, collagen, vimentin or fibrinogen may be cross-reactant to citrullinated RA candidate autoantigens.

Antigen-specific autoantibodies in RA may be present years before clinical disease onset of arthritis, and their precise role in the initiation or perpetuation of the characteristic articular immune processes is currently unclear. The situation for autoantibodies was in similar poorly understood for decades until an unanticipated reduction of RA disease activity could be achieved by therapeutic B cell depletion using anti-CD20 therapy. While anti-CD20 therapy may affect the regeneration of autoantibody producing cells, the investigators aim in the present study to reduce potential oral trigger mechanisms or antigens for cross-reactant autoreactive B cell or plasma cell populations. The study follows the concept of improved RA disease activity by minimization of any inflammatory stimuli associated with periodontitis, e.g. by any underlying microbial colonization, the amount of microbial foreign antigens, achieved by standard oral hygienic means, full mouth disinfection plus adjuvant short term antibiotic therapy in established periodontitis.

Inclusion criteria

• Written informed consent
• Age 18 years or older
• Diagnosis of rheumatoid arthritis according to the ACR/EULAR 2010 classification criteria plus both serological, high titer (>3x ULN) rheumatoid factor and CCP antibody titer
• Severe chronic periodontitis (clinical attachment loss >/= 5mm at two separate locations)
• DAS 28 > 4.2 at screening and inclusion (within 28 days after screening) and 1 out of two additional disease activity criteria:

• Synovial hyperplasia >22/66 points on basis of 22 joints, or at least 1/3 of the maximum score when analyzes in at least selected 5 joints of interest OR
• Serum CRP > 10 mg/l at screening and at inclusion
• Stable doses for >=3 months, if currently under synthetic or recombinant disease modifying anti-rheumatic drugs. If under anti-CD20 treatment: last rituximab infusion >90 days before inclusion.
• Systemic corticosteroids <= 10 mg and stable for at least 14 days
• Nonsteroidal-antirheumatic drugs and peripheral analgesics at stable doses for at least 14 days

Exclusion criteria

• Intolerance to amoxicillin und azithromycin (EBV infection, lymphatic leukemia, exanthema), general hypersensitivity to any beta-lactam antibiotics, intolerance to metronidazole or local anaesthesia
• Current intake of allopurinol or probenicid, oral anticoagulation, disulfiram, phenobarbital phenytoin, lithium or ciclosporin
• Seizures
• Severe cardial electric conduction blockade
• Recent myocardial infraction or instable coronary vessel disease, non-compensated myocardial insufficiency or heart failure
• Non-compensated arterial hypertension
• Genetic cholinesterase deficiency
• General hemorrhagic diathesis or intake of oral anticoagulants
• Intake of monoaminooxidase inhibitors or tricyclic antidepressants
• Liver insufficiency
• Renal failure (eGFR < 30 ml/min)
• Hemoglobin <10 g/dl
• Leukocytes < 3/nl
• Neutrophils < 1/nl
• Platelets < 100/nl
• ALAT oder ASAT > 3x ULN
• Pregnancy or breastfeeding
• Psychiatric or any other condition which could, to the opinion of the investigator, interfere with the compliance of this protocol