Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial. The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand X-rays of patients with rheumatoid arthritis. Prophylaxis with doxycycline (Vibramycin) in colorectal surgery. Effect of azidocillin, erythromycin, clindamycin and doxycycline on postoperative complications after surgical removal of impacted mandibular third molars. The end of antibiotic treatment in adults with acute sinusitis-like complaints in general practice? A placebo-controlled double-blind randomized doxycycline trial. Therapeutic efficacy and tolerability of brodimoprim in comparison with doxycycline in acute sinusitis in adults. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction.
To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.
                In this placebo-controlled trial, obese women (n = 431) ages 45-64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals.
                Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean +/- SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 +/- 0.42 mm versus 0.24 +/- 0.54 mm); after 30 months, it was 33% less (0.30 +/- 0.60 mm versus 0.45 +/- 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a > or = 20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a > or = 20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.
                Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee. Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs.
                This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein.
                The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01).
                The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs. Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifies symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness of doxycycline on pain and daily functioning in symptomatic knee osteoarthritis.
                A 24-week, randomised, triple-blind, placebo controlled trial on the symptomatic effectiveness of doxycycline twice a day 100 mg in knee osteoarthritis patients according to the clinical and radiological American College of Rheumatology classification criteria. The primary endpoint was the difference in the proportion of participants in both study groups achieving a clinical response defined by the OMERACT-OARSI set of responder criteria. Secondary endpoints included pain, stiffness, daily functioning, patient global assessment, quality of life, osteoarthritis-related medication and side effects.
                232 patients were randomly assigned. At study end, 31% of participants met the primary endpoint in both groups. Except for more adverse events in the doxycycline group, no differences were also found on the secondary endpoints.
                Doxycycline is not effective in reducing symptoms in knee osteoarthritis patients over a 24-week study period, but is associated with an increased risk of adverse events. Although a possible structure-modifying effect of doxycycline was previously suggested, this is not accompanied by symptom relief in the short and medium term. Dutch Trial Register no NTR1111. To test the hypotheses that the progression of joint space narrowing behaves differently from the progression of erosions and that clinically and radiologically assessed soft tissue swelling relates more to diffuse cartilage loss than to erosive damage.
                Radiographs and clinical data were obtained from 28 patients in a prospective, multicentre, randomized, placebo-controlled trial of prednisolone 7.5 mg daily over 2 yr. Radiographic scoring included the Larsen score, joint space narrowing and soft tissue swelling. Clinical joint inflammation in the hands was assessed every 3 months and cumulative synovitis score over the period of study was then calculated for each joint. The placebo-treated patients and the prednisolone-treated patients were analysed separately. The Larsen scores were compared after log transformation [transformed score=log(10) (original score+1)]. Changes in Larsen scores and joint space narrowing scores were compared with the cumulative presence of clinical synovitis and radiological soft tissue swelling using the correlation coefficient.
                There was a difference in the rate of progression in the Larsen score between placebo- and prednisolone-treated patients, but there was no significant difference in the rate of joint space loss. In placebo-treated patients, measures of synovitis correlated more strongly with progression of joint space narrowing than with changes in the Larsen score. In prednisolone-treated patients there was no correlation between clinical synovitis and change in Larsen score (r=0.029) and only a slight and non-significant correlation with joint space narrowing (r=0.127). Radiographic evidence of soft tissue swelling remained correlated with joint space narrowing (r=0.279, P:<0.001) but was not correlated with change in Larsen score (r=-0.113, P:<0.001 for difference between correlations). The correlation between Larsen score progression and joint space narrowing seen in the non-treated patients was completely abolished in the glucocorticoid-treated group (r=-0.003).
                The progression of joint space narrowing behaves differently from the progression of erosions. Prednisolone slows (or even stops) the progression of erosions (as assessed by the Larsen score) while making no difference to the progression of cartilage loss (as assessed by joint space narrowing). The results also suggest that synovitis, whether measured clinically or radiologically, is more closely related to diffuse cartilage loss than to erosion progression. Any link between synovitis and erosions is abolished by glucocorticoid therapy while the link between synovitis and cartilage loss is not, pointing to at least two different mechanisms for these observed radiological features. A prospective randomized double-blind study comprising 118 patients was performed to evaluate the effects of doxycycline as a prophylactic antimicrobial in elective colonic surgery. Fifty-eight patients were treated and 60 were controls. 200 mg of active substance or placebo was given 4-6 hours before operation and 100 mg daily for the next five postoperative days. Levels of doxycycline in serum and tissues were determined and related to the MIC-values of the contaminants. A significantly lower incidence of abdominal wound sepsis, intra-abdominal complications and septicaemia was found in the doxycycline group (12.4%) compared to the controls (45%). The positive effects were most pronounced in the non-contaminated cases, and especially in the cases with negative wound culture at operation. In order to evaluate the effect of prophylaxis in clinical routine an open study comprising 182 patients was carried out. In the group of patients receiving adequate prophylaxis (159 patients) the abdominal wound sepsis rate was 8.1%. 11 other patients who had received doxycycline preoperatively for some time because of intra-abdominal infection developed wound sepsis in 63.4%. In 12 patients where incomplete or no prophylaxis was given, the wound sepsis rate was 33.2%. The frequency of abdominal septic complications did not differ between non-contaminated, 10.9%, and contaminated operations, 13.8%, partly because of the topical application of ampicillin in some of the patients belonging to the latter category. Preoperative treatment with doxycycline because of some intra-abdominal was evidently the single risk factor associated with a high septic complication rate. No adverse ecological effects were seen during the 19 months study. Treatment of osteitis after surgical removal of the third molar of the mandible is still a clinical problem. A total of 140 patients undergoing operations for removal of an impacted third molar of the mandible, were included in a double-blind study. Placebo or antibiotics - azidocillin, erythromycin, clindamycin and doxycycline - were given to the patients preoperatively and for the following 7 days. The concentrations in serum, alveolar serum and mandibular bone were measured and the postoperative courses - pain, trismus, swelling and wound-healing - were recorded. No correlation was obtained between the antibiotic concentration and the postoperative complaints, except in the azidocillin group on day 2, in which fewer complaints were noticed in patients with high concentrations of the drug at the time of operations. The 80 patients in the antibiotic groups responded significantly better with respect to wound-healing than the 60 patients in the placebo groups. Only 15 operations lasted more than 15 min and the three of them which subsequently resulted in alveolitis were in the placebo groups. Antibiotics significantly reduced pain on day 7 postoperatively. In general, no statistically significant differences in trismus and swelling could be demonstrated between the patient groups. However, there was a significant difference between the placebo and doxycycline groups with respect to swelling (day 2 postoperative, P < 0.01; day 5 postoperative, P < 0.05). Thus systemically administered antibiotics offered only slight advantages in routine operations of impacted third mandibular molars, but could decrease the rate of infections after traumatic operations. Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains.
                To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice.
                The effects of doxycycline in a placebo-controlled, double-blind, randomized trial were assessed in adults consulting their general practitioner (GP) with complaints after a common cold or influenza, pain in the head when bending forward, purulent nasal discharge, predominantly unilateral maxillary pain, toothache, or pain when chewing. Primary outcome events were the resolution of facial pain and the resumption of daily activities. Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios. The follow-up period was 42 days.
                No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group. However, the adjusted hazard ratio for the group receiving doxycycline was 1.17 (95% CI = 0.87-1.57) for the resolution of pain and 1.31 (95% CI = 0.96-1.78) for the resumption of daily activities. After 10 days, 85% of all patients reported improvement and 60% were completely cured. Side effects were reported by 17% of the doxycycline-treated group, with two patients withdrawing because of side effects.
                Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults. To compare efficacy and tolerability of brodimoprim tablets with doxycycline tablets in adults with acute sinusitis.
                Open, randomized, controlled phase III study, with parallel groups.
                Of the 70 enrolled patients, 56 adults of both sexes with a mean age of 33 years were evaluable. STUDY DRUGS: One brodimoprim 200mg tablet or one doxycycline 100mg tablet was administered once daily for 8 to 12 days (on the first treatment day all patients received the loading dose consisting of 2 tablets of the corresponding compound).
                In the brodimoprim group 96.4% of the patients were judged cured/improved; in the doxycycline group 96.2%. BACTERIOLOGICAL OUTCOME: Eradication of the causative pathogen/s was achieved in 87.5% of the patients treated with brodimoprim and in 60% of the doxycycline group. SAFETY OUTCOME: Tolerability was judged as very good/good in 89.7% of the patients treated with brodimoprim and in all patients receiving doxycycline. Gastrointestinal skin, CNS and various other reactions were reported by 13 patients; 3 of them had to discontinue treatment. Discontinuation of therapy: 8 more patients withdrew from the study due to inactivity of the compound or reasons unrelated to the drugs.
                Brodimoprim was shown to be effective in the treatment of acute sinusitis in adults, its efficacy being equal to that of doxycycline. The assessments showed a positive clinical response to the medication in 96.4% of the patients treated with brodimoprim and 96.2% of the patients taking doxycycline. Both compounds were well tolerated and all side effects were of mild nature and reversible. The aim was to investigate the effect of low dose doxycycline (20 mg) therapy in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy.
                The randomized prospective study enrolled 150 patients (300 eyes) who have chronic meibomian gland dysfunction and who didn't respond to lid hygiene and topical therapy for more than 2 months. All topical therapy was stopped for at least 2 weeks prior to beginning the study. After conducting the tear break up time test (TBUT) and Schirmer test, the authors randomly divided the patients into three groups a high dose group (doxycycline, 200 mg, twice a day), a low dose group (doxycycline, 20 mg, twice a day) and a control group (placebo). After one month, the author repeated the TBUT and Schirmer tests, and analyzed the degree of symptomatic improvement.
                Compared to the control group, both the high and low dose group showed statistically significant differences after treatment in TBUT, Schirmer test, the number of symptoms reported and the degree of improvement of subjective symptoms. However, there was no statistically significant difference between the high and low dose group after treatment in TBUT (9.42 +/- 2.87 sec, 9.54 +/- 1.58 sec, p=0.726), Schirmer test (19.98 +/- 4.05 mm, 19.65 +/- 5.02 mm, p=0.624), the number of symptoms reported (1.45 +/- 0.62, 1.53 +/- 0.52, p=0.304), as well as the degree of improvement of subjective symptoms (p=0.288). The high dose group (18 patients, 39.13%) reported side effects more frequently than did the low dose group (8 patients, 17.39%) (P=0.002).
                Low dose doxycycline (20 mg twice a day) therapy was effective in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy.
In this update, the strength of evidence for effectiveness outcomes was improved from low to moderate and we confirmed that the symptomatic benefit of doxycycline is minimal to non-existent, while the small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. The CIs of the summary estimates now exclude any clinically relevant difference in improvement of symptoms and the small benefit in terms of joint space narrowing does not outweigh the harms.