Efficacy Of Subantimicrobial Dose Doxycycline Research Articles

Evaluation of the efficacy of subantimicrobial dose doxycycline in rosacea: a systematic review of clinical trials and meta‐analysis

Low-dose doxycycline (SDD) is an antimicrobial agent that appears to improve common inflammatory skin diseases. Few data are available regarding the overall effectiveness, appropriate length of treatment and optimal patient selection for rosacea. We therefore reviewed the efficacy of sub-antimicrobial doses of SDD in papulopustular rosacea (PPR) and aimed to determine the most suitable patients for this approach. From July to September 2019, we carried out a comprehensive search of literature from five databases, using a combination of "rosacea" AND "doxycycline". Our search yielded 532 potentially relevant studies. Our meta-analysis showed no significant difference between SDD and a comparator (RR: 1.12, 95% CI: 0.78-1.62, I2 = 86%). Subgroup analysis of studies comparing doxycycline with placebo yielded a clear difference in favor of doxycycline (RR: 1.45, 95% CI: 1.22-1.72, I2 = 31%), while subgroup analysis of studies comparing active drugs revealed no difference between interventions (RR: 0.52, 95% CI: 0.17-1.63, I2 = 90%). There is strong evidence that SDD is more effective than placebo. However, other drugs such as minocycline or isotretinoin have shown outcomes at least similar to that of SDD. We suggest that the anti-inflammatory properties of SDD may be of more value for mild cases of rosacea than for moderate to severe cases, for which higher (antimicrobial) doses of doxycycline may be a more suitable choice.

Host modulation therapy with anti-inflammatory agents.

Host modulation therapy refers to a treatment concept in which drug therapies are used as an adjunct to conventional periodontal treatment to ameliorate destructive aspects of the host inflammatory response. This strategy is not new in the treatment of periodontitis. Previously, nonsteroidal anti-inflammatory drugs have been investigated in this regard, with evidence of reductions in alveolar bone resorption when these drugs are used for prolonged periods of time. However, the risk of significant unwanted effects precludes the use of both nonselective nonsteroidal anti-inflammatory drugs and the selective cyclooxygenase-2 inhibitors as adjunctive treatments for periodontitis. Currently, the only available adjunctive host response modulator that is licensed for the treatment of periodontitis is subantimicrobial dose doxycycline, which functions as an inhibitor of matrix metalloproteinases. Although clinical benefits have been shown in carefully conducted randomized controlled trials, the efficacy of subantimicrobial dose doxycycline in routine clinical practice has yet to be determined. Anti-cytokine therapies have been developed for use in the treatment of rheumatoid arthritis, the pathogenesis of which bears many similarities to that of periodontitis; however, the significant risk of unwanted effects (as well as cost and lack of human trials in the treatment of periodontal diseases) precludes the use of any of the currently available anti-cytokine therapies in the treatment of periodontitis. The identification of pro-resolving lipid mediators as well as small molecule biologicals that influence inflammatory responses offers the best potential, at the present time, for the development of novel host response modulators in periodontal therapy, but much research remains to be done to confirm safety and efficacy.

Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves' Orbitopathy.

Aim. To study the efficacy and safety of subantimicrobial dose (SD) doxycycline(50 mg/d) in patients with active and moderate-to-severe Graves' orbitopathy (GO). Methods. Thirteen patients with active and moderate-to-severe GO received once daily oral doxycycline (50 mg/d) for 12 wk. Treatment response at 24 wk was used as the primary outcome, measured by a composite of improvement in Clinical Activity Score (CAS), diplopia, motility, soft tissue swelling, proptosis, and eyelid aperture. Secondary outcome was the change of quality of life score (QoL, including visual functioning subscale and appearance subscale). Adverse events were also recorded. Results. Overall improvement was noted in eight out of 13 patients (61.5%, 95% CI 31.6%–86.1%). Both CAS and soft tissue swelling significantly ameliorated in eight patients at 24 wk. Five patients (38.5%) had improvement in ocular motility of ≥8 degrees. Eyelid aperture (46.2%) also decreased remarkably. For QoL, a significant improvement in appearance subscale (P = 0.008) was noted during the study, whereas no difference was observed in visual functioning subscale (P = 0.21). Two patients reported mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective and safe for the treatment of active and moderate-to-severe GO. It might serve as a new promising therapeutic strategy for GO. This trial is registered with NCT01727973.

Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in chronic periodontitis

To evaluate the effectiveness of subantimicrobial-dose doxycycline (SDD) as an adjunct to scaling and root planing (SRP) treatment against the nitrosative stress of moderate to advanced chronic periodontitis. Adults with untreated chronic periodontitis (n=174) were randomly administered SRP+SDD (n=87) (20 mg of doxycycline twice daily) or SRP+placebo (n=87) treatment for 3 months. At baseline and after 3 months, the probing depths (PD), bleeding on probing (BOP) and clinical attachment level (CAL) were measured, and a gingivomucosal biopsy was collected to assay the induction of nitric oxide synthase (iNOS) and 3-nitrotyrosine (3NT), and blood was collected to assay for total nitrites and nitrates (NO(x)) and 3NT. Compared to baseline, at the completion of treatment, significant decreases in the levels of tissue iNOS and 3NT and serum NO(x) and 3NT were observed in both groups. SRP+SDD yielded a greater reduction in the gingivomucosal and serum nitrosative stress markers than did SRP+placebo. PD, BOP, and CAL reduction were correlated with the nitrosative stress parameters. On a short-term basis, SDD therapy may be used as an adjunct to SRP treatment against nitrosative stress in moderate to advanced chronic periodontitis.

Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD)

Periodontitis, the most common chronic inflammatory condition known to mankind, is a disease that results in the destruction of tooth supporting tissues. Periodontitis is initiated by a bacterial biofilm on the tooth surface below the gingival margin. Until fairly recently it was assumed that the bacteria were the primary cause of tissue destruction, however, a large body of research has revealed that it is the patient's immune response that is actually responsible for the majority of the breakdown of tooth supporting tissues. Contemporary thinking suggests that successful, long term management of chronic periodontitis may combine both local mechanical and antimicrobial strategies to reduce the microbial bio-burden along with modulation of the host, patient's excessive, immuno-inflammatory response to the bacterial exposure known as host modulatory therapy (HMT). Based on extensive literature documenting the enzymatic inhibition and related anti-inflammatory properties of the tetracyclines, a new drug was developed as a host modulatory agent and approved by the United States Food and Drug Administration (FDA) for use as an adjunct to conventional scaling and root planing for the treatment of chronic periodontitis. A subantimicrobial dose of doxycycline (SDD) at 20 mg (Periostat ®) has been found to be a safe and effective adjunct when taken twice daily for at least 3 months and up to 24 months in randomized placebo controlled clinical trials. Periostat ® is currently the only FDA approved inhibitor of the matrix metalloproteinases implicated in the plaque-induced pathologic degradation of connective tissue collagen of the periodontal supporting structures. This review paper begins with a brief description of the disease process known as periodontitis followed by an extensive review of the Phase I–IV clinical trial data that established the safety and efficacy of sub-antimicrobial dose doxycycline (SDD) as an adjunct to scaling and root planing for the treatment of periodontitis.

Effects of Scaling and Root Planing and Subantimicrobial Dose Doxycycline on Gingival Crevicular Fluid Levels of Matrix Metalloproteinase‐8, ‐13 and Serum Levels of HsCRP in Patients With Chronic Periodontitis

This study evaluates the efficacy of subantimicrobial dose doxycycline (SDD) in conjunction with scaling and root planing (SRP) on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)-8 and -13 and on serum levels of high-sensitivity C-reactive protein (HsCRP) in patients with chronic periodontitis (CP). A total of 41 patients with CP and 17 healthy individuals were included in this randomized controlled trial. CP patients were randomly distributed into two groups. Study groups were established as Group I with SRP+placebo, Group II with SRP+SDD, and Group III as control. All CP patients received two regimens of SRP and Group II patients also received SDD for 6 weeks. At baseline and 6 weeks, GCF and blood were collected and clinical indices were recorded. The HsCRP level was assayed in the plasma on a nephelometer. The GCF levels of MMPs were assayed by an enzyme-linked immunosorbent assay. Statistically significant differences in plaque index, gingival index (GI), probing depth (PD), GCF volumes, GCF MMP levels, and serum levels of HsCRP between pre-treatment and post-treatment were noted in both groups. Between groups there was a statistically significant decrease in PD, GI, and GCF levels of MMP-8 favoring the group receiving SDD adjunctive to SRP (P <0.05). In this study, greater improvement was detected for PD, GI, and GCF levels of MMP-8 when using SRP+SDD compared to SRP+placebo.

Efficacy of sub‐antimicrobial dose doxycycline in post‐menopausal women: clinical outcomes

Journal of Clinical PeriodontologyVolume 34, Issue 12 p. 1097-1097 Free Access Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes This article corrects the following: Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes Richard A. Reinhardt, Julie A. Stoner, Lorne M. Golub, Mark S. Wolff, His-Ming Lee, Trudy A. Meinberg, James C. Lynch, Maria E. Ryan, Timo Sorsa, Jeffrey B. Payne, Volume 34Issue 9Journal of Clinical Periodontology pages: 768-775 First Published online: August 16, 2007 First published: 15 November 2007 https://doi.org/10.1111/j.1600-051X.2007.01156_1.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Odds ratios in the text of this paper were incorrectly published as per cents. For example, the odds of more progressive disease based on relative clinical attachment level are 19% lower for the SDD group compared with the placebo group, but the odds ratio (relating the odds for the SDD group to the odds for the placebo group) should be listed as 0.81 instead of 0.81%. A similar correction applies to all odds ratio values that are listed numerically as a per cent in the abstract, the results section, and in the last paragraph of the discussion section. The fifth author is Hsi-Ming Lee, not His-Ming Lee. The last visit in Table 1 was 24 months, not 14 months. We apologize for these errors. Reference Reinhardt, R. A., Stoner, J. A., Golub, L. M., Wolff, M. S., Lee, H.-M., Meinberg, T. A., Lynch, J. C., Ryan, M. E., Sorsa, T. & Payne, J. B. (2007) Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes. Journal of Clinical Periodontology, 34, 768– 775. Volume34, Issue12December 2007Pages 1097-1097 ReferencesRelatedInformation

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

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. 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. 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. 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). SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone.