BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as adisease-modifying agent for the treatment of osteoarthritis, with the potentialto slow cartilage degeneration. This is an update of a Cochrane review firstpublished in 2009. OBJECTIVES: To examine the effects of doxycycline comparedwith placebo or no intervention on pain and function in people withosteoarthritis of the hip or knee. SEARCH METHODS: We searched CENTRAL (TheCochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008,with an update performed at 16 March 2012. In addition, we checked conferenceproceedings, reference lists, and contacted authors. SELECTION CRITERIA: Weincluded studies if they were randomised or quasi-randomised controlled trialsthat compared doxycycline at any dosage and any formulation with placebo or nointervention in people with osteoarthritis of the knee or hip. DATA COLLECTIONAND ANALYSIS: We extracted data in duplicate. We contacted investigators toobtain missing outcome information. We calculated differences in means atfollow-up between experimental and control groups for continuous outcomes andrisk ratios (RR) for binary outcomes. MAIN RESULTS: We identified one additional trial (232 participants) and included two trials (663 participants) in thisupdate. The methodological quality and the quality of reporting were consideredmoderate. At end of treatment, clinical outcomes were similar between the twotreatment groups, with an effect size of -0.05 (95% confidence interval (CI)-0.22 to 0.13), corresponding to a difference in pain scores between doxycycline and control of -0.1 cm (95% CI -0.6 to 0.3 cm) on a 10-cm visual analogue scale, or 32% versus 29% improvement from baseline (difference 3%; 95% CI -5% to 10%).The effect size for function was -0.07 (95% CI -0.25 to 0.10), corresponding to adifference between doxycycline and control of -0.2 (95% CI -0.5 to 0.2) on theWestern Ontario and McMaster Universities Arthritis Index (WOMAC) disabilitysubscale with a range of 0 to 10, or 24% versus 21% improvement (difference 3%;95% CI -3% to 10%). The difference in changes in minimum joint space narrowingassessed in one trial was in favour of doxycycline (-0.15 mm; 95% CI -0.28 to-0.02 mm), which corresponds to a small effect size of -0.23 standard deviationunits (95% CI -0.44 to -0.02). More participants withdrew from the doxycyclinegroup compared with placebo due to adverse events (RR 2.28; 95% CI 1.06 to 4.90).There was no evidence that participants in the doxycycline group experienced moreserious adverse events than those in the placebo group, but the estimate wasimprecise (RR 1.07; 95% CI 0.68 to 1.68). AUTHORS' CONCLUSIONS: In this update,the strength of evidence for effectiveness outcomes was improved from low tomoderate 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 thesummary estimates now exclude any clinically relevant difference in improvementof symptoms and the small benefit in terms of joint space narrowing does notoutweigh the harms.
Doxycycline for osteoarthritis of the knee or hip
Rutjes, Anne;
2012-01-01
Abstract
BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as adisease-modifying agent for the treatment of osteoarthritis, with the potentialto slow cartilage degeneration. This is an update of a Cochrane review firstpublished in 2009. OBJECTIVES: To examine the effects of doxycycline comparedwith placebo or no intervention on pain and function in people withosteoarthritis of the hip or knee. SEARCH METHODS: We searched CENTRAL (TheCochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008,with an update performed at 16 March 2012. In addition, we checked conferenceproceedings, reference lists, and contacted authors. SELECTION CRITERIA: Weincluded studies if they were randomised or quasi-randomised controlled trialsthat compared doxycycline at any dosage and any formulation with placebo or nointervention in people with osteoarthritis of the knee or hip. DATA COLLECTIONAND ANALYSIS: We extracted data in duplicate. We contacted investigators toobtain missing outcome information. We calculated differences in means atfollow-up between experimental and control groups for continuous outcomes andrisk ratios (RR) for binary outcomes. MAIN RESULTS: We identified one additional trial (232 participants) and included two trials (663 participants) in thisupdate. The methodological quality and the quality of reporting were consideredmoderate. At end of treatment, clinical outcomes were similar between the twotreatment groups, with an effect size of -0.05 (95% confidence interval (CI)-0.22 to 0.13), corresponding to a difference in pain scores between doxycycline and control of -0.1 cm (95% CI -0.6 to 0.3 cm) on a 10-cm visual analogue scale, or 32% versus 29% improvement from baseline (difference 3%; 95% CI -5% to 10%).The effect size for function was -0.07 (95% CI -0.25 to 0.10), corresponding to adifference between doxycycline and control of -0.2 (95% CI -0.5 to 0.2) on theWestern Ontario and McMaster Universities Arthritis Index (WOMAC) disabilitysubscale with a range of 0 to 10, or 24% versus 21% improvement (difference 3%;95% CI -3% to 10%). The difference in changes in minimum joint space narrowingassessed in one trial was in favour of doxycycline (-0.15 mm; 95% CI -0.28 to-0.02 mm), which corresponds to a small effect size of -0.23 standard deviationunits (95% CI -0.44 to -0.02). More participants withdrew from the doxycyclinegroup compared with placebo due to adverse events (RR 2.28; 95% CI 1.06 to 4.90).There was no evidence that participants in the doxycycline group experienced moreserious adverse events than those in the placebo group, but the estimate wasimprecise (RR 1.07; 95% CI 0.68 to 1.68). AUTHORS' CONCLUSIONS: In this update,the strength of evidence for effectiveness outcomes was improved from low tomoderate 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 thesummary estimates now exclude any clinically relevant difference in improvementof symptoms and the small benefit in terms of joint space narrowing does notoutweigh the harms.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
