Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease.

BACKGROUND: Previous studies showed that adjunctive subantimicrobial dose doxycycline (SDD; 20 mg, twice daily) provides significant clinical benefits to scaling and root planing (SRP). A modified-release SDD formulation containing 40 mg doxycycline (SDD-40) to be taken once daily has been developed. The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis. METHODS: A 9-month, double-masked, randomized, placebo-controlled, multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis. Subjects were treated by SRP and randomized to receive SDD-40 or placebo for 9 months with evaluations at 3, 6, and 9 months. RESULTS: Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points. At month 9, at sites with baseline probing depths (PD) > or =6 mm, 72% to 76% of sites in the SDD-40 group demonstrated clinically significant PD reductions and clinical attachment level (CAL) gains > or =2 mm compared to 56% to 58% of sites in the placebo group (P <0.0001); 48% to 52% of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32% of sites in the placebo group (P <0.0001). In moderate sites (baseline PD 4 to 6 mm), adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL (all time points: P <0.05), PD (3 months: P = 0.002; 6 and 9 months: P = 0.001), and bleeding on probing (BOP) (3 months: P <0.01; 6 months: P <0.02; 9 months: P <0.05). In deep sites (baseline PD > or =7 mm), SDD-40 provided significant benefits over control for mean CAL (3 months: P <0.05; 6 and 9 months: P <0.01), PD (all time points: P <0.001), and BOP (3 months: P <0.05; 6 months: not statistically significant; 9 months: P <0.05). Compliance with study medication was high (>92%) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group. CONCLUSION: SDD-40 used as an adjunct to SRP resulted in significantly greater clinical benefits than SRP alone in the treatment of periodontitis.

Subantimicrobial dose doxycycline in the treatment of recurrent oral aphthous ulceration: a pilot study.

BACKGROUND: Recurrent oral aphthous ulceration (ROAU) is a common problem that can result in considerable pain and distress for patients. The aim of this pilot study was to evaluate the role of subantimicrobial dose doxycycline (SDD - 20 mg doxycycline twice daily) in the management of patients with ROAU. METHODS: 50 patients with ROAU were randomly allocated to treatment with SDD or placebo for 90 days. Daily ulcer diaries were completed by the participants to record the number of new ulcers and the pain associated with the ulcers. RESULTS: There were significantly more days with no new ulcers in the SDD group (80.4 +/- 5.9) than the placebo group (69.8 +/- 18.7; P=0.04). Strong trends were observed towards fewer new ulcers per day, fewer new ulcers over the 90-day period, and more days with no pain in the SDD group compared with the placebo group (P=0.06-0.08). CONCLUSION: SDD shows promise as potential therapy in the management of ROAU, though this needs to be confirmed in further studies.

Adjunctive subantimicrobial dose doxycycline in smokers and non-smokers with chronic periodontitis.

OBJECTIVES: Previous studies have demonstrated the clinical benefits of sub-antimicrobial dose doxycycline (SDD) in the treatment of chronic periodontitis (CP). The aim of this study was to retrospectively evaluate the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of smokers and non-smokers with CP. MATERIAL AND METHODS: A meta-analysis of two previously reported clinical studies was undertaken. Both were 9-month, double-blind, randomized, placebo-controlled, multi-centre clinical trials that investigated the efficacy of SDD (20 mg doxycycline twice daily) in combination with SRP in subjects with moderate-severe CP. 36.9% of the combined study population were smokers. Three hundred and ninety-two subjects were included in the meta-analysis, which evaluated per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline and the total number of sites with attachment gains and PD reductions > or =2 and > or =3 mm from baseline in four subgroups: smokers/SDD; smokers/placebo; non-smokers/SDD; non-smokers/placebo. RESULTS: A hierarchical treatment response was observed, with non-smokers who received SDD demonstrating the greatest CAL gains and PD reductions. Smokers who received placebo demonstrated the smallest clinical improvements following treatment. Smokers who received SDD demonstrated an intermediate treatment response that was broadly equivalent to that seen in non-smokers who received placebo. In sites with baseline PD 4-6 mm, month 9 CAL gains were 19-45% better in non-smokers who received SDD compared with all other subgroups (p<0.05), and were 21% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). Furthermore, month 9 PD reductions were 21-53% greater in non-smokers who received SDD compared with all other subgroups (p<0.01), and were 26% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). CONCLUSION: Adjunctive SDD enhances therapeutic outcomes compared with SRP alone, resulting in clinical benefit in both smokers and non-smokers with CP.

Adjunctive subantimicrobial dose doxycycline in the management of institutionalised geriatric patients with chronic periodontitis.

OBJECTIVE: To assess the efficacy of subantimicrobial dose doxycycline (SDD; 20 mg doxycycline twice daily) as an adjunct to scaling and root planing (SRP) in the treatment of moderate-severe chronic periodontitis (CP) in institutionalised elderly patients aged 65 years or older. BACKGROUND: Previous studies have shown that SDD is of clinical benefit in the treatment of CP. However, the benefits of SDD in geriatric populations (65+ years) have not been determined. MATERIAL AND METHODS: A 9-month, double-blind, randomised, placebo-controlled pilot study was conducted. 24 institutionalised geriatric patients (65 years or older) with evidence of CP manifested by baseline clinical attachment levels (CAL) 5-9 mm, probing depths (PD) 4-9 mm and bleeding on probing (BOP) were recruited. At baseline, patients were treated by a standardised episode of SRP, and randomised to receive either adjunctive SDD or placebo. Full mouth PD and CAL were measured using the manual UNC-15 periodontal probe at 3, 6, and 9 months post-baseline to assess the response to treatment. Periodontal sites were stratified by baseline PD value: sites with PD 4-5 mm were considered moderately diseased and sites with PD > or = 6 mm severely diseased. RESULTS: The SRP + placebo resulted in PD reductions similar to those reported previously in the literature. At all time-points and in both moderate and deep sites, SRP + SDD resulted in significantly greater PD reductions relative to baseline than SRP + placebo. At month 9, in moderate sites, mean PD reductions of 1.57 +/- 0.11 mm were reported in the adjunctive SDD group, compared with 0.63 +/- 0.11 mm in the adjunctive placebo group (p < 0.001). In deep sites at month 9, mean PD reductions of 3.22 +/- 0.29 mm were reported in the adjunctive SDD group, compared with 0.98 +/- 0.31 mm in the adjunctive placebo group (p < 0.05). Similar improvements were observed for CAL in the SDD group compared with the placebo group. Significantly lower BOP scores were also recorded at month 9 in the SDD group (7.5%) compared with the placebo group (71.2%) (p < 0.01). CONCLUSION: SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone.

Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis: a multicenter trial.

BACKGROUND: Previous studies have shown that subantimicrobial dose doxycycline (SDD) is of clinical benefit in the treatment of chronic periodontitis (CP). The aim of this study was to further assess the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of CP. METHODS: A double-blind, randomized, placebo-controlled, multicenter clinical study was conducted to test the efficacy of SDD (20 mg doxycycline B.I.D.) in combination with SRP in subjects with moderate to severe CP. Two-hundred ten subjects were treated with a standardized episode of SRP and randomized to receive either adjunctive SDD or placebo for 9 months. Efficacy parameters included per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, and the total number of sites with attachment gains and probing depth reductions > or = 2 mm and > or = 3 mm from baseline. RESULTS: In periodontal sites with PD 4 to 6 mm and > or = 7 mm (N = 209, intent-to-treat population), mean improvements in CAL and PD were greater following SRP with adjunctive SDD than SRP with placebo, achieving statistical significance in all baseline disease categories at month 9 (P < 0.05). At month 9, 42.3% of sites in the SDD group demonstrated CAL gain > or = 2 mm compared to 32.0% of sites in the placebo group (P < 0.01). CAL gain > or = 3 mm was seen in 15.4% of sites in the SDD group compared to 10.6% of sites in the placebo group (P < 0.05). When considering the same thresholds of change in PD, 42.9% of sites in the SDD group compared to 31.1% of sites in the placebo group demonstrated PD reduction > or = 2 mm (P < 0.01), and 15.4% of sites in the SDD group compared to 9.1% of sites in the placebo group demonstrated PD reduction > or = 3 mm (P < 0.01). CONCLUSION: Adjunctive subantimicrobial dose doxycycline enhances scaling and root planing. It results in statistically significant attachment gains and probing depth reductions over and above those achieved by scaling and root planing with placebo.

Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review.

BACKGROUND: Subantimicrobial dose doxycycline (SDD--20 mg doxycycline twice daily) is indicated as an adjunctive treatment for periodontitis. Doxycycline downregulates the activity of matrix metalloproteinases (MMPs), key destructive enzymes in periodontal disease. Current understanding of periodontal pathogenesis suggests that MMPs play a major role in the destruction of periodontal tissues, leading to the clinical signs of periodontitis. Research supports that downregulation of MMPs by SDD confers benefit to patients with periodontitis. METHOD: We review the clinical, microbiological and safety data relating to the use of SDD in patients with periodontitis, and consider the historical events that led to the development of adjunctive SDD as a treatment for periodontitis. RESULTS: Studies have shown that SDD, when prescribed as an adjunct to scaling and root planing (SRP), results in statistically and clinically significant gains in clinical attachment levels and reductions in probing depths over and above those that are achieved by SRP alone. SRP must be thorough and performed to the highest standard to maximise the benefits of adjunctive SDD. SDD does not result in antibacterial effects, or lead to the development of resistant strains or the acquisition of multiantibiotic resistance. The frequency of adverse events is low, and does not differ significantly from placebo. CONCLUSIONS: Adjunctive SDD confers clinical benefit to patients with periodontitis. A comprehensive treatment strategy is suggested, involving patient education and motivation, reduction of the bacterial burden by SRP, host response modulation with SDD, and periodontal risk factor modification.

Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis.

BACKGROUND: Severe, generalized periodontitis is a form of chronic periodontitis that appears to be associated with an exaggerated host response. Little information is available on the benefits of using adjunctive host modulation in the management of this form of periodontal disease. METHODS: Thirty subjects < or = 45 years of age with severe, generalized periodontitis received subgingival debridement and oral hygiene instructions each week for 4 weeks, plus 6 months of adjunctive subantimicrobial doxycycline (SDD) or placebo. Periodontal status was monitored at baseline, and at 1, 3, 5.25, and 8.25 months following completion of the hygiene sessions. Maintenance therapy was performed at 3, 5.25, and 8.25 months for both groups. RESULTS: Ten subjects in each group completed all phases of the study. Subgingival debridement plus adjunctive SDD reduced deep pockets (> or =7 mm at baseline) by an average of 3.02 mm after 9 months versus 1.42 mm for the placebo group. A significant clinical response was seen in both groups as soon as 1 month, but the response was always clinically and statistically greater in the SDD group. In the SDD group, nearly 40% of 237 pockets > or =7 mm were reduced by > or =4 mm, and 55% were reduced by > or =3 mm. In addition, only 2 pockets deepened by > or =4 mm in the SDD group versus 10 in the placebo group. CONCLUSIONS: The supplementation of hygienist-delivered full mouth subgingival and supragingival debridement with a host-modulating agent, SDD, provides clinically and statistically significant benefits in the reduction of deep pockets in patients with severe, generalized periodontitis. In addition, adjunctive SDD is more effective than a placebo in preventing further increases in probing depth.