Table 1.
Therapeutic Impact of DMARDs on Periodontitis.
| Host Modulatory Agent | Type of Study | Follow-up | Clinical Outcomes | Subclinical Outcomes | Authors and Year |
|---|---|---|---|---|---|
| Conventional synthetic DMARDs | |||||
| Cs DMARDs (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine) or anti-TNF-α therapy and synthetic DMARDs | Cross-sectional | Not available | Methotrexate + leflunomide exhibited significantly higher percentage of interproximal sites (31.6%) with clinical attachment loss ≥4 mm vs. methotrexate + other conventional DMARD (10%) or leflunomide + other conventional DMARD (13.3%). | Treatment with >1 DMARD was associated with the presence of Porphyromonas gingivalis. | Romero-Sanchez et al. (2017) |
| Cs DMARDs (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine) or biological DMARDs (TNF-α inhibitors, IL-1 inhibitor, anti-B-cell agent) combined with methotrexate | Prospective cohort | 16 mo | 80% of early untreated RA and 85% of chronic RA groups had periodontitis vs. 40% of controls at baseline. No statistical difference in periodontal parameters in intra- and intergroup analyses. | Patients with early RA had higher presence of P. gingivalis at follow-up. | Äyräväinen et al. (2017) |
| Cs DMARDs (methotrexate, hydroxychloroquine, sulfasalazine) | Prospective cohort | 4 wk after SRP | Additional PPD reduction of 0.8 mm (RA group) vs. 0.6 mm (control group). Additional CAL gain of 1.1 mm (RA group) vs. 0.7 mm (control group). Higher PPD reduction was associated with combined synthetic DMARDs over methotrexate as monotherapy. | No significant difference of RA activity (DAS28-ESR) among groups of synthetic DMARDs. | Jung et al. (2018) |
| Biological DMARDs | |||||
| TNF-α inhibitors (infliximab, adalimumab, etanercept) | Prospective cohort | 6 mo | Significant improvement in % sites with BOP, PPD reduction (−1.49 ± 0.22 mm), and CAL gain (0.5 ± 0.26 mm) vs. baseline. | Significant reduction in RA activity (DAS28), inflammatory (ESR, CRP), and serologic (ACPAs) parameters. | Codrina et al. (2017) |
| TNF-α inhibitors (etanercept, infliximab, adalimumab, golimumab) or IL-6 receptor inhibitors (tocilizumab) | Prospective cohort | 6 mo | Significant improvements in GI, BOP, and PPD reduction in both groups vs. baseline. Significant additional CAL gain of 0.1 mm vs. baseline only for tocilizumab-treated group. Greater GI decrease in tocilizumab-treated group. | TNF inhibitors and tocilizumab were associated with significant decrease in DAS28-CRP, serum levels of anti-CCP antibodies, rheumatoid factor, and MMP-3. | Kobayashi et al. (2015) |
| TNF-α inhibitors (infliximab, etanercept, and adalimumab) with synthetic DMARDs (methotrexate, hydroxychloroquine, leflunomide, sulfasalazine) | Prospective cohort | 6 wk after SRP | Significant improvements in PPD reduction, CAL gain, BOP, PI, and GI were observed for all groups receiving periodontal therapy/SRP alone; significant reduction in PPD (0.2 mm), BOP, and GI vs. baseline/anti-TNF-α + SRP; significant reduction in PPD (0.4 mm), BOP, and GI and significant CAL gain (0.3 mm) vs. baseline. | Significant reduction in ESR for the groups receiving anti-TNF-α therapy over those receiving only synthetic DMARDs. No significant decrease in DAS28 for all groups. | Ortiz et al. (2009) |
| TNF-α inhibitor (infliximab) | Cross-sectional | Not available | Patients receiving infliximab had higher modified GI and papillary GI but no significant differences in PPD and CAL vs. patients not receiving infliximab. | No significant differences were found for DAS28 between the groups. | Pers et al. (2008) |
| TNF-α inhibitor (infliximab) | Prospective cohort | 9 mo | Patients receiving infliximab with methotrexate had higher MGI and PGI but higher CAL gain (6.27 ± 0.97 vs. 5.22 ± 1.05 mm) vs. baseline. | Not investigated | Pers et al. (2008) |
| TNF-α inhibitor (adalimumab, infliximab) | Prospective cohort | 30 d | Significant increase in GI vs. baseline. No significant changes for BOP, PPD, and CAL vs. baseline. | Significant decrease in GCF volume, GCF levels of IL-1β and IL-8, salivary IL-8 and MCP-1 levels vs. baseline. Decrease in CRP, ESR, and DAS28 vs. baseline. | Üstün et al. (2013) |
| Methotrexate, leflunomide, TNF-α inhibitors, IL-6 antagonists, rituximab | Cross-sectional | Not available | Significantly higher BOP and PBI in patients receiving methotrexate + TNF-α inhibitors vs. patients receiving leflunomide. Higher BOP in patients receiving methotrexate + TNF-α inhibitors vs. patients receiving methotrexate and rituximab. | Prevalence of P. gingivalis and Treponema denticola was associated with medication group | Ziebolz et al. (2018) |
| JAK inhibitor (baricitinib) | Prospective cohort | 6 mo | Significant reduction in GI, PPD (0.8 mm), and % sites with PPD ≥4 mm (3.5%). | Significant decrease in RA activity (DAS28-CRP), inflammation (CRP-ESR), and serologic markers (ACPA, RF) vs. baseline | Ancuţa et al. (2020) |
| Anti-B lymphocyte immunotherapy (rituximab) | Cross sectional | Not available | Patients receiving rituximab had significantly lower marginal GI, PPD (Δ = 0.6 mm), and clinical attachment loss (Δ = 0.3 mm) than patients not receiving rituximab. | Not investigated | Coat et al. (2015) |
| Anti-B lymphocyte immunotherapy (rituximab) | Prospective cohort | 6 mo (subgroup assessed up to 4 y) | No significant changes in MGI, PBI, and PI after 6 mo of rituximab. Significantly higher PPD reduction of 0.2 mm after rituximab vs. baseline. Significant CAL gain of 0.3 mm after rituximab vs. baseline. Tendency for further improvements in periodontal parameters from 6 mo to 4 y of rituximab treatment. | Not investigated | Coat et al. (2015) |
| IL-23 and IL-12 inhibitor (ustekinumab) | Case report | 1 y | Refractory severe periodontitis associated with leukocyte adhesion deficiency was resolved. Decrease in BOP after 3 wk of treatment with ustekinumab. | Gingival expression of IL-23 and IL-17 became undetectable after 3 wk of treatment with ustekinumab. | Moutsopoulos et al. (2017) |
ACPA, anti–citrullinated protein antibody; anti-CCP, anti–cyclic citrullinated peptides; BOP, bleeding on probing; CAL, clinical attachment level; CRP, C-reactive protein; Cs, conventional synthetic; DAS28, disease activity score 28; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; GCF, gingival crevicular fluid; GI, gingival index; IL, interleukin; MCP-1, monocyte chemoattractant protein 1; MGI, marginal gingival index; MMP-3, metalloproteinase 3; PBI, papillary bleeding index; PGI, papillary gingival index; PI, plaque index; PPD, probing pocket depth; RA, rheumatoid arthritis; RF, rheumatoid factor; SRP, scaling and root planing.