Systematic review and meta-analysis on the adjunctive use of host immune modulators in non-surgical periodontal treatment in healthy and systemically compromised patients

Considering the central role of inflammation in the pathogenesis of periodontitis, the combination of NSPT with different agents that can modulate the host immune-inflammatory response has been proposed to enhance the outcomes of NSPT. The aim of this paper is to systematically review the literature on the efficacy of systemic host modulators (HMs) as adjuncts to non-surgical periodontal therapy (NSPT) in improving pocket depth (PD) reduction and clinical attachment level (CAL) gain in healthy and systemically compromised patients. RCTs with ≥ 3 months follow-up were independently searched by two reviewers. Meta-analysis was performed when ≥ 3 studies on the same HM were identified. The quality of the evidence was rated according to the GRADE approach to rate the certainty of evidence. 38 articles were included in the qualitative assessment and 27 of them were included in the meta-analysis. There is low/very low evidence that the adjunctive use of sub-antimicrobial dose of doxycicline, melatonin and the combination of omega-3 and low dose aspirin (in type 2 diabetic patients) to NSPT would improve PD and/or CAL. Conflicting evidence is available on the efficacy of probiotics. Future studies controlling for confounding factors, using composite outcomes to define the endpoint of therapy and considering not only the patient- but also as the site-specific effect of systemic HMs are warranted. The dosage, posology and long-term effect of HMs still need to be clarified, also in association to the presence of systemic conditions potentially affecting the response to HMs administration.