Disease severity, debridement approach and timing of drug modify outcomes of adjunctive azithromycin in non-surgical management of chronic periodontitis: a multivariate meta-analysis

Abstract

BackgroundPast meta-analyses have shown adjunctive systemic Azithromycin (AZI) to provide minor clinical benefits in scaling and root surface debridement (S/RSD). However, these have not considered the covariance of key outcome parameters; probing pocket depth (PPD) and Clinical Attachment Level (CAL) or systematically examined some potential sources of heterogeneity.AimTo jointly synthesize 6-month outcomes of systemic AZI as adjunctive to S/RSD in chronic periodontitis and investigate 3 potential sources of heterogeneity.MethodsFour databases were searched for suitable randomized controlled clinical trials (RCTs). Standardized mean differences (SMD) in PPD and CAL between AZI\u2009+\u2009S/RSD and S/RSD alone, at 6-month follow-up were computed. Within-study covariances of PPD and CAL were derived from reported multiple time-point data. A multivariate meta-analysis with random effects jointly modelled PPD and CAL, factoring in their covariance. This model included 3 moderators with interaction effects; timing of AZI initiation (pre-therapy/post-therapy), type of S/RSD [full-mouth debridement (FMD)/partial-mouth debridement (PMD)], and baseline study-level mean values of PPD/CAL.ResultsAmong 276 abstracts, 11 observations from 9 RCTs qualified for meta-analysis. Within-study correlation-coefficients of PPD with CAL significantly increased with increasing study-level baseline mean values (Spearman’s r\u2009=\u20090.79, p\u2009<\u20090.01). The full multivariate meta-analysis model showed significant effects for the 3 moderators (Q statistic\u2009=\u2009150.03, p\u2009<\u20090.01), retained significant residual heterogeneity (Q statistic\u2009=\u200988.50, p\u2009<\u20090.01) but outperformed (Likelihood- ratio statistic\u2009=\u2009102.95, p\u2009<\u20090.01,) a null-model with no moderators (Q statistic\u2009=\u2009201.5, p\u2009<\u20090.01). A significant effect was seen only on the SMD for PPD (estimate\u2009=\u20091.16\u2009mm, 95% CI: 0.27\u2009mm–2.07\u2009mm\u2009mm, p\u2009=\u20090.01) but not CAL (estimate\u2009=\u20090.17\u2009mm, 95% CI: -0.92\u2009mm-1.26\u2009mm, p\u2009=\u20090.76). SMD in PPD positively interacted with study baseline value (estimate\u2009=\u20090.11, 95% CI: 0.08–0.15, p\u2009<\u20090.01). Significant negative interactions of SMD in PPD with PMD (estimate\u2009=\u2009−\u20091.25\u2009mm, 95% CI: -1.73\u2009mm- -0.78\u2009mm, p\u2009<\u20090.01) and pre-therapy drug initiation (estimate\u2009=\u2009−\u20091.18\u2009mm, 95% CI: -1.48\u2009mm--0.87\u2009mm, p\u2009<\u20090.01) were evident.ConclusionJoint synthesis of PPD and CAL showed, at 6-months, AZI\u2009+\u2009S/RSD provided a benefit over S/RSD alone for PPD alone when correlation with CAL was accounted for. Deeper study-level baseline PPD, FMD type of S/RSD, and post-therapy drug initiation associated with greater PPD reduction.