Resumen de Assessment of Interleukin-6 Receptor Inhibition Therapy on Periodontal Condition in Patients With Rheumatoid Arthritis and Chronic Periodontitis
Background: Overproduction of interleukin (IL)-6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL-6 receptor (IL-6R) inhibition therapy on the periodontal condition of patients with RA and CP.
Methods: The study participants were 28 patients with RA and CP during treatment with IL-6R inhibitor, and 27 patients with RA and CP during treatment without IL-6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL-6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2).
Results: No differences were observed between the groups in any parameter values at T1, except for serum IL-6 levels. The anti�IL-6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL-6 and matrix metalloproteinase (MMP)-3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti�IL-6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP-3 levels and those in BOP (P <0.05).
Conclusion: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL-6R inhibitor.
Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by inflammation of synovium and breakdown of bone and cartilage in the joints, leading to functional disability. The prevalence of RA is estimated to be �0.5% in the world, and RA affects women about three times as often as it affects men.1 It has been suggested that similarities in clinical and pathologic features exist between RA and periodontitis.2,3 A number of clinical studies have indicated that patients with RA are more likely to exhibit periodontitis than those without RA.4-7 Individuals with RA have shown increased levels of periodontal tissue breakdown compared with control individuals.5,6 Additionally, patients with periodontitis have a higher prevalence of RA than those without periodontitis,7-9 suggesting an association between the two inflammatory diseases.
A similar profile of cytokines has been involved in the pathogenesis of RA and periodontitis.2 In particular, interleukin (IL)-6 has been suggested as one of the most potent cytokines associated with these two diseases.10,11 It has been documented that increased levels of IL-6 were found in inflamed gingival tissue, gingival crevicular fluid (GCF), and plasma from patients with periodontitis.12,13 It was also reported that serum levels of IL-6 were decreased following periodontal treatment.14,15 Likewise, IL-6 levels were higher in serum, synovial tissue, and synovial fluid of patients with RA than those of patients with non-inflammatory arthritis.16-18 Furthermore, the authors demonstrated that serum levels of IL-6 were positively correlated with disease activity of RA.19 These findings suggest that constitutive overproduction of IL-6 plays a pathologic role in RA and periodontitis.
Tocilizumab (TCZ) is a humanized monoclonal anti-human IL-6 receptor (IL-6R) antibody with specificity for the soluble and membrane-expressed IL-6R, which inhibits IL-6�mediated pro-inflammatory activity.20 TCZ is a recently approved drug and has been shown to be effective in adults with moderate to severe active RA.21-24 Clinical efficacy of TCZ monotherapy or combination therapy with TCZ plus methotrexate (MTX), a first choice of the disease-modifying antirheumatic drugs (DMARDs), was shown in the CHARISMA (the Chugai Humanized Anti-Human Recombinant Interleukin-6 Monoclonal Antibody),21 OPTION (the tocilizumab pivotal trial in methotrexate inadequate responders),22 and SATORI (Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate) studies.23 Additionally, the radiographic benefit of TCZ monotherapy was demonstrated in SAMURAI (Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor).24 However, there is no information to date on the effect of TCZ medication on the periodontal condition. It has been documented that no long-term results of TCZ were obtained in human studies and that some serious infection cases were observed after TCZ medication, although no significant adverse reaction was reported.21-24 These observations imply that recruitment of patients with RA for evaluation before and after TCZ medication may have some difficulties. The aim of the present study is to assess the effect of treatment with TCZ on the periodontal condition, as determined by gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL), and rheumatologic profiles as well as serum levels of cytokines and inflammatory markers in the patients with RA and chronic periodontitis (CP). Furthermore, serum levels of immunoglobulin (Ig)G antibodies against periodontopathic bacteria were evaluated because of their possible relation to the periodontal condition.
