Treatment of stage I–III periodontitis—The EFP S3 level clinical practice guideline

Intervention

Supragingival dental biofilm control can be achieved by mechanical and chemical means. Mechanical plaque control is mainly performed by tooth brushing, either with manual or powered toothbrushes or with supplemental interdental cleaning using dental floss, interdental brushes, oral irrigators, wood sticks, etc. As adjuncts to mechanical plaque control, antiseptic agents, delivered in different formats, such as dentifrices and mouth rinses have been recommended. Furthermore, other agents aimed to reduce gingival inflammation have also been used adjunctively to mechanical biofilm control, such as probiotics, anti‐inflammatory agents and antioxidant micronutrients.

Available evidence

Even though oral hygiene interventions and other preventive measurements for gingivitis control were not specifically addressed in the systematic reviews prepared for this Workshop to Develop Guidelines for the treatment of periodontitis, evidence can be drawn from the XI European Workshop in Periodontology (2014) (Chapple et al., 2015) and the systematic review on oral hygiene practices for the prevention and treatment of gingivitis (Van der Weijden & Slot, 2015). This available evidence supports the following:

• Professional oral hygiene instructions (OHI) should be provided to reduce plaque and gingivitis. Re‐enforcement of OHI may provide additional benefits.

• Manual or power tooth brushing are recommended as a primary means of reducing plaque and gingivitis. The benefits of tooth brushing out‐weigh any potential risks.

• When gingival inflammation is present, inter‐dental cleaning, preferably with interdental brushes (IDBs) should be professionally taught to patients. Clinicians may suggest other inter‐dental cleaning devices/methods when the use of IDBs is not appropriate.

Intervention

Oral hygiene instructions (OHI) and patient motivation in oral hygiene practices should be an integral part of the patient management during all stages of periodontal treatment (Tonetti et al., 2015). Different behavioural interventions, as well as communication and educational methods, have been proposed to improve and maintain the patient's plaque control over time (Sanz & Meyle, 2010). See additional information in the next section on “Methods of motivation.”

Intervention

Several different psychological interventions based on social cognitive theories, behavioural principles and motivational interviewing (MI) have been applied to improve OHI adherence in patients with periodontal diseases. The available evidence has not demonstrated that these psychological interventions based on cognitive constructs and motivational interviewing principles provided by oral health professionals have improved the patient's oral hygiene performance as measured by the reduction of plaque and bleeding scores over time.

Available evidence

The evidence includes two RCTs on MI (199 patients) and three RCTs on psychological interventions based on social cognitive theories and feedback (1,517 patients).

Risk of bias

The overall body of evidence was assessed at high risk of bias (four RCTs high and one RCT low).

Consistency

The majority of the studies found no significant additional benefit implementing psychological interventions in conjunction with OHI.

Clinical relevance and effect size

The reported effect size was not considered clinically relevant.

Balance of benefit and harm

Benefit and harm were not reported, and due to the fact that different health professionals were involved to provide interventions, no conclusion could be drawn.

Economic considerations

These studies did not assess a cost–benefit evaluation in spite of the expected additional cost related to the psychological intervention.

Patient preferences

No proper information was available to assess this issue.

Applicability

A psychological approach needs special training to be effectively performed.

Intervention

The removal of the supragingival dental biofilm and calcified deposits (calculus) (here identified under the term “professional mechanical plaque removal” (PMPR)) is considered an essential component in the primary (Chapple et al., 2018) and secondary (Sanz et al., 2015) prevention of periodontitis as well as within the basic treatment of plaque‐induced periodontal diseases (van der Weijden & Slot, 2011). Since the presence of retentive factors, either associated with the tooth anatomy or more frequently, due to inadequate restorative margins, are often associated with gingival inflammation and/or periodontal attachment loss, they should be prevented/eliminated to reduce their impact on periodontal health.

Available evidence

Even though these interventions were not specifically addressed in the systematic reviews prepared for this Workshop to develop guidelines for the treatment of periodontitis, indirect evidence can be found in the 2014 European Workshop on Prevention, in which the role of PMPR was addressed both in primary prevention (Needleman et al., 2015) or in supportive periodontal care (SPC) (Trombelli et al., 2015). Some additional evidence can be found to support both procedures, as part of periodontitis therapy. A split‐mouth RCT, with a follow‐up of 450 days in 25 subjects, concluded that the performance of supragingival debridement, before subgingival debridement, decreased subgingival treatment needs and maintained the periodontal stability over time (Gomes, Romagna, Rossi, Corvello, & Angst, 2014). In addition, supragingival debridement may induce beneficial changes in the subgingival microbiota (Ximénez‐Fyvie et al., 2000). Moreover, it has been established that retentive factors may increase the risk of worsening the periodontal condition (Broadbent, Williams, Thomson, & Williams, 2006; Demarco et al., 2013; Lang, Kiel, & Anderhalden, 1983).

Intervention

Smoking and diabetes are two proven risk factors in the etiopathogenesis of periodontitis (Papapanou et al., 2018), and therefore, their control should be an integral component in the treatment of these patients. Interventions for risk factor control have aimed to educate and advice patients for behavioural change aimed to reduce them and in specific cases to refer them for adequate medical therapy. Other relevant factors associated with healthy lifestyles (stress reduction, dietary counselling, weight loss or increased physical activities) may also be part of the overall strategy for reducing patient's risk factors.

Available evidence

In the systematic review (Ramseier et al., 2020), the authors have identified 13 relevant guidelines for interventions for tobacco smoking cessation, promotion of diabetes control, physical exercise (activity), change of diet, carbohydrate (dietary sugar reduction) and weight loss. In addition, 25 clinical studies were found that assess the impact of (some of) these interventions in gingivitis/periodontitis patients.

Risk of bias

It is explained specifically for each intervention.

Consistency

The heterogeneity in study design precludes more consistent findings, but adequate consistency may be found for studies on smoking cessation and diabetes control.

Clinical relevance and effect size

No meta‐analysis was performed; effect sizes can be found in the individual studies.

Balance of benefit and harm

In addition to periodontal benefits, all the tested interventions represent a relevant beneficial health impact.

Economic considerations

The various studies do not indicate a cost–benefit evaluation. However, it cannot be discarded an additional cost related to the psychological intervention. However, the systemic health benefits that can be obtained from these interventions, if they are successful, would represent reduced cost of healthcare services in different comorbidities.

Patient preferences

Interventions are heterogeneous, but the potential systemic health benefits may favour preference for them.

Applicability

Demonstrated with studies testing large groups from the general population; the practicality of routine use is still to be demonstrated.

Intervention

Periodontitis patients may benefit from smoking cessation interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. Interventions consist of brief counselling and may include patient referral for advanced counselling and pharmacotherapy.

Available evidence

In the systematic review (Ramseier et al., 2020), six prospective studies of 6‐ to 24‐month duration and performed at university setting were identified. Different interventions were tested (smoking cessation counselling, 5 A's [ask, advise, assess, assist, and arrange], cognitive behavioural therapy [CBT], motivational interview, brief interventions, nicotine replacement therapies). In three of the studies, the intervention was programmed in parallel with non‐surgical periodontal therapy (NSPT) and followed by SPC, in one study SPC patients were included and, in another, patients in NSPT and in SPC were compared; in one study, it was unclear. The success of smoking cessation was considered as moderate (4%–30% after 1–2 years), except in one study. Two studies demonstrated benefits in periodontal outcomes, when comparing former smokers to smokers and oscillators.

Additional factors have been discussed in the overall evaluation of risk factor control.

Intervention

Periodontitis patients may benefit from diabetes control interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. These interventions consist of patient education as well as brief dietary counselling and, in situations of hyperglycaemia, the patient's referral for glycaemic control.

Available evidence

In the systematic review (Ramseier et al., 2020), two studies on the impact of diabetes control interventions in periodontitis patients were identified, two of them 6‐month RCTs, all of them performed at university settings. Periodontal interventions were not clearly defined. Different interventions were tested, including individual lifestyle counselling, dietary changes and oral health education. Some improvements were observed in the intervention groups, in terms of periodontal outcomes.

Additional factors have been discussed in the overall evaluation of risk factor control.

Intervention

Overall evidence from the medical literature suggests that the promotion of physical exercise (activity) interventions may improve both treatment and the long‐term management of chronic non‐communicable diseases. In periodontitis patients, the promotion may consist of patient education and counselling tailored to the patients' age and general health.

Available evidence

In the systematic review (Ramseier et al., 2020), two 12‐week studies on the impact of physical exercise (activity) interventions in periodontitis patients were identified, one RCT (testing education with comprehensive yogic interventions followed by yoga exercises) and one prospective study (with briefing followed by physical exercises; the control group was a dietary intervention), performed at university settings. Periodontal interventions were not clearly defined, although in the yoga study, standard therapy was delivered (by not described) in periodontitis patients, while no periodontal therapy was provided in the second study. Both studies reported improved periodontal parameters, including bleeding scores and probing depth changes, after 12 weeks (although in the yoga study also, the influence on psychological stress could not be discarded).

Additional factors have been discussed in the overall evaluation of risk factor control.

Intervention

Periodontitis patients may benefit from dietary counselling interventions to improve periodontal treatment outcomes and the maintenance of periodontal stability. These interventions may consist of patient education including brief dietary advices and in specific cases patient's referral to a nutrition specialist.

Available evidence

In the systematic review (Ramseier et al., 2020), seven studies on the impact of dietary counselling (mainly addressing lower fat intake, less free sugars and salt intake, increase in fruit and vegetable intake) in periodontitis (with or without other comorbidities) patients were identified: three RCTs (6 months, 8 weeks, 4 weeks) and four prospective studies (12 months, 24 weeks, 12 weeks, 4 weeks), performed at hospital and university settings. Periodontal interventions were not clearly defined, although in the 6‐month RCT, periodontal treatment was part of the protocol. Some studies showed significant improvements in periodontal parameters, but the RCT with the longest follow‐up was not able to identify significant benefits (Zare Javid, Seal, Heasman, & Moynihan, 2014).

In the systematic review (Ramseier et al., 2020), two studies specifically on the impact of dietary counselling aiming at carbohydrate (free sugars) reduction in gingivitis/periodontitis patients were identified, one 4‐week RCT (including also gingivitis patients) and one 24‐week prospective study. Periodontal interventions were not clearly defined. Both studies reported improved gingival indices.

Additional factors have been discussed in the overall evaluation of risk factor control.

Intervention

Available evidence suggests that weight loss interventions may improve both the treatment and long‐term outcome of chronic non‐communicable diseases. In periodontitis patients, these interventions may consist of specific educational messages tailored to the patients' age and general health. These should be supported with positive behavioural change towards healthier diets and increase in physical activity (exercise).

Available evidence

In the systematic review (Ramseier et al., 2020), five prospective studies, in obese gingivitis/periodontitis patients, on the impact of weight loss interventions were identified, with different follow‐ups (18 months, 12 months, 24 weeks and two studies of 12 weeks). Periodontal interventions were not clearly defined. Intensity of lifestyle modifications aiming at weight loss interventions ranged from a briefing, followed by counselling in dietary change, to an 8‐week high‐fibre, low‐fat diet, or a weight reduction programme with diet and exercise‐related lifestyle modifications. Three studies reported beneficial periodontal outcomes and, the other two, no differences.

Additional factors have been discussed in the overall evaluation of risk factor control.

Intervention

Subgingival instrumentation aims at reducing soft tissue inflammation by removing hard and soft deposits from the tooth surface. The endpoint of treatment is pocket closure, defined by probing pocket depth (PPD) ≤4 mm and absence of bleeding on probing (BOP).

Available evidence

One RCT on 169 patients with 3‐month outcomes addressed the PICOS question. Further 11 prospective studies (n = 258) with a follow‐up of ≥6 months which considered baseline measures and post‐treatment reductions in probing pocket depth (primary outcome) and bleeding on probing and percentage of closed pockets (secondary outcomes) were analysed.

Risk of bias

Study quality assessment identified a low risk of bias in all but one study, which had a high risk of bias.

Consistency

Evidence was consistent across all 11 studies that were included in the pre‐ and post‐treatment analysis and was therefore considered strong. Patient‐reported outcomes were inconsistently reported and adverse events, when reported, were rare. No indications of publication bias were observed but heterogeneity was high.

Clinical relevance and effect size

The evidence suggested a mean reduction of PPD of 1.7 mm at 6/8 months, a mean proportion of closed pockets of 74% and a mean reduction of BOP of 63%. Deeper sites (>6 mm) demonstrated a greater mean PPD reduction of 2.6 mm.

Balance of benefits and harm

An overall consideration of the benefit versus harm of subgingival instrumentation supports the strength of the recommendation.

Ethical considerations

Evaluation of the efficacy of subgingival debridement is ethically challenging as it would entail comparison with no subgingival intervention. Due to the lack of relevant RCTs, prospective studies were included and their data analysed.

Applicability

The majority of studies were conducted in well‐controlled research environments and included specifically selected populations, that is those with no systemic disease. While results from studies involving populations with systemic diseases were not included in the systematic review, there is a consensus that subgingival instrumentation is efficacious in these groups (Sanz et al., 2018, 2019), but the magnitude of the effect requires further study.

The evidence presented illustrates “efficacy” rather than “effectiveness”; therefore, generalizability to general dental practice settings is unclear.

Intervention

Numerous types of instruments are available to perform subgingival instrumentation.

Available evidence

Four RCTs (n = 132) with a low overall risk of bias were included. Findings were evaluated at 6/8 months for PPD reduction (primary outcome) and clinical attachment level (CAL) gain (secondary outcome).

Risk of bias

Study quality assessment identified all four studies to be at low risk of bias.

Consistency

The evidence demonstrated that outcomes of treatment were not dependent on the type of instrument employed. The evidence was considered strong and consistent. No indications of publication bias were observed but heterogeneity was high.

Clinical relevance

No clinically or statistically significant differences were observed between the different types of instruments.

Balance of benefits and harm

The use of all types of instruments is technique‐sensitive and therefore requires specific training. Patient‐reported outcomes and adverse events were inconsistently reported. If present, no obvious differences between hand and powered instruments in terms of post‐operative sensitivity were noted.

Ethical considerations

There is a potential ethical dilemma in that patient preference may conflict with the clinician's preference in terms of type of instrument. Patient autonomy should be respected.

Economic considerations

Cost‐effectiveness has not been evaluated in these studies. Furthermore, there is no evidence that the use of one type of instrument is superior in terms of requisite treatment time.

Applicability

The majority of studies were conducted in well‐controlled research environments, in specifically selected populations and under local anaesthetic. Clinicians should be aware that new instrument choices (i.e. mini instruments) were not evaluated in the available studies. The choice of instrument should be based upon the experience/skills and preference of the operator together with patient preference.

Intervention

Subgingival instrumentation has traditionally been delivered during multiple sessions (e.g. quadrant‐wise). As an alternative, full‐mouth protocols have been suggested. Full‐mouth protocols included single stage and two‐stage therapy within 24 hr; however, protocols including antiseptics (full‐mouth disinfection) were not included in this analysis.

Available evidence

Eight RCTs (n = 212) with a follow‐up of ≥6 months were included demonstrating a low risk of bias. Outcome measures reported were PPD reduction (primary outcome), CAL gain, BOP reduction and pocket closure (secondary outcomes).

Risk of bias

Study quality assessment identified all eight studies at low risk of bias.

Consistency

The evidence suggested that outcomes of treatment were not dependent on the type of delivery (protocol) employed. The evidence was considered strong and consistent. No indications of publication bias were observed, and heterogeneity was low. The results confirm the findings of a recent Cochrane systematic review (Eberhard, Jepsen, Jervoe‐Storm, Needleman, & Worthington, 2015).

Clinical relevance

No substantial differences were observed between the two treatment modalities.

Balance of benefits and harm

Clinicians should be aware that there is evidence of systemic implications (e.g. acute systemic inflammatory response) with full‐mouth protocols. Thus, such an approach should always include careful consideration of the general health status of the patient.

Ethical considerations

There is a potential ethical dilemma in that patient preference may conflict with the clinician's recommendation in terms of mode of treatment delivery. Patient autonomy should be respected.

Legal considerations

Potential adverse systemic effects of full‐mouth treatment protocols in certain risk patients should be considered.

Economic considerations

Limited evidence on the cost‐effectiveness of different modes of delivery is available.

Patient preferences

Patient‐reported outcomes were inconsistently reported, and there is no evidence supporting one approach over the other. Reports of increased discomfort and side effects, evident in studies on full‐mouth disinfection, were not included in the present analysis.

Applicability

The majority of studies were conducted in well‐controlled environments, included specifically selected populations and were undertaken in a number of different continents.

Intervention

Lasers offer the potential to improve outcomes of subgingival root surface treatment protocols when used as adjuncts to traditional root surface instrumentation. Depending upon the wavelength and settings employed, some lasers can ablate subgingival calculus and exert antimicrobial effects. The evidence reported to inform the current guidelines has grouped lasers into two main wavelength categories: lasers with a wavelength range of 2,780–2,940 nm and lasers with a wavelength range of 810–980 nm.

Available evidence

Evidence was available from five RCTs (total n = 147) with a follow‐up of ≥6 months and a single laser application. Only RCTs reporting mean PPD changes were considered and this recommendation is made in the light of this approach to the systematic review.

Risk of bias

The majority of studies displayed unclear risk of bias.

Consistency

Studies differed in terms of laser type, tip diameter, wavelength, mode of periodontal treatment, number of treated sites, population and several possible combinations of these parameters.

Clinical relevance and effect size

There is insufficient evidence to recommend adjunctive application of lasers to subgingival instrumentation.

Balance of benefits and harm

The majority of the studies did not report on potential harm/adverse effects.

Economic considerations

Additional costs associated with adjunctive laser therapy may not be justified.

Patient preferences

Patient‐reported outcomes were rarely reported.

Applicability

The majority of studies were conducted in university settings, included specifically selected populations and were undertaken in a number of different countries.

Intervention

Adjunctive antimicrobial photodynamic therapy (aPDT) is an approach used to improve the antimicrobial effects of traditional root surface decontamination methods. It functions by attaching a photosensitizing dye to the normally impermeable outer cell membrane of Gram‐negative bacteria and then uses laser light to generate reactive oxygen species through the membrane‐bound dye to locally destroy those bacteria.

Available evidence

Evidence was available from five RCTs (n = 121) with a follow‐up of ≥6 months and a single aPDT application. Only RCTs reporting mean PPD changes were included in the meta‐analysis, and this recommendation is made in the light of this approach to the systematic review.

Risk of bias

The majority of studies displayed unclear risk of bias.

Consistency

Substantial heterogeneity across the studies was identified, in terms of laser type, photosensitizer, wavelength, mode of periodontal treatment, number of treated sites, population and several possible combinations of these parameters.

Clinical relevance and effect size

No benefits were observed with the adjunctive application of aPDT.

Balance of benefits and harm

The majority of the studies reported on adverse events with no harm associated with the adjunctive application of aPDT.

Economic considerations

Additional costs associated with adjunctive laser therapy may not be justified.

Patient preferences

Patient‐reported outcomes were rarely reported, and there is no evidence supporting one approach over the other.

Applicability

All studies were conducted in well controlled university settings or specialist centres, included specifically selected populations and were undertaken in a number of different countries.

Intervention

Statins are known to have pleiotropic pharmacological effects in addition to their hypolipidemic properties. These include antioxidant and anti‐inflammatory effects, the stimulation of angiogenesis, improvements in endothelial function and the positive regulation of bone formation pathways (Adam & Laufs, 2008; Mennickent, Bravo, Calvo, & Avello, 2008; Petit et al., 2019). Recent evidence suggests that statins may also attenuate periodontal inflammation, as reflected by decreases in pro‐inflammatory and increases in anti‐inflammatory mediators within the gingival crevicular fluid (GCF) of patients with periodontitis (Cicek Ari et al., 2016).

Available evidence

Twelve placebo‐controlled RCTs (n = 753), all derived from the same research group, assessed the effect of local statin gels in adjunctive non‐surgical therapy for infrabony or furcation Class II defects. PPD reduction (primary outcome) was reported at 6 and 9 months for 1.2% atorvastatin (6 RCTs, n = 180), 1.2% simvastatin gel (five RCTs, n = 118) and 1.2% rosuvastatin gel (four RCTs, n = 122). Meta‐analysis was performed in nine RCTs (n = 607).

Risk of bias

There was a moderate overall risk of bias in the studies analysed. Three of 12 studies presented with a high risk of bias in at least one domain. One study was moderately underpowered. While pharmaceutical companies provided the statins in the included studies, the level of involvement of industry in the analysis and interpretation of the results is unclear.

Consistency

Meta‐analysis of nine RCTs where statins had been applied to a single site per patient demonstrated that adjunctive local application of 1.2% statin gels in infrabony defects led to a mean difference in PPD reduction of 1.83 mm (95% confidence interval (CI) [1.31; 2.36]) at 6 months and of 2.25 mm (95% CI [1.88; 2.61]) at 9 months. Only one study investigated locally delivered statins in Class II furcation defects.

Clinical relevance

Although the mean estimates suggested a clinically meaningful benefit from adding statin gels to subgingival instrumentation, there was a large prediction interval for PPD reduction at 6 months (−0.08 mm to 3.74 mm) and the I ² (95.1%) indicating wide heterogeneity of data and therefore caution needs to be adopted when assessing the efficacy of statins. While the prediction interval at 9 months (1.16–3.34 mm) improved over 6‐month results, heterogeneity (I ² statistic) of 65.4% still indicated moderate inconsistency in results. Since the outcomes of the different statin gels were considered as one group during the meta‐analysis, it is not possible to draw definitive conclusions on which statin offered higher efficacy.

Balance of benefits and harms

All studies included in the review reported that patients tolerated local statins well, without any complications, adverse reactions/side effects or allergic symptoms.

Economic considerations

There is an additional cost associated with the use of statins that is borne by the patient.

Ethical and legal considerations

The statin formulations included in the systematic review are “off‐label” and an approved formulation with appropriate good manufacturing practice quality control (Good Manufacturing Practice, GMP) and patient's safety validation is not available.

Applicability

The same research group published all data within the RCTs, thereby restricting the generalizability of the results, which need to be confirmed in future larger (multicentre) RCTs by independent groups, with multilevel analyses to account for potential confounding factors (e.g. medical history, smoking history). In addition, future studies will need to clarify which type of statin is more effective.

Intervention

Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (FAO/WHO). It has been suggested that probiotics may alter the ecology of micro‐environmental niches such as periodontal pockets, and as such, they may disrupt an established dysbiosis. This may re‐establish a symbiotic flora and a beneficial interaction with the host via several mechanisms including modulation of the immune‐inflammatory response, regulation of antibacterial substances and exclusion of potential pathogens via nutritional and spatial competition (Gatej, Gully, Gibson, & Bartold, 2017). This guideline does not include evidence on the use of probiotics in supportive periodontal therapy.

Available evidence

Five placebo‐controlled RCTs (n = 176) assessed the adjunctive effect of probiotics to subgingival instrumentation. Two studies from the same group used a preparation containing L. ramnosus SP1 (2 × 10⁷ colony forming units). Two other RCTs from another research group used a preparation containing L. reuteri. One study evaluated a combination of S. oralis KJ3, S. uberis KJ2 and S. rattus JH145. Meta‐analysis was performed on PPD reduction (primary outcome) at 6 months.

Risk of bias

All studies had an overall low risk of bias. Two out of the five studies declared industrial sponsorship, and three received the probiotics from industry.

Consistency

Meta‐analysis of five RCTs demonstrated that, compared with placebo, treatment with probiotics resulted in a mean difference in PPD reduction of 0.38 mm (95% CI [−0.14; 0.90]) at 6 months. The confidence interval and I ² statistic (93.3%) suggested considerable heterogeneity for the effect of the treatment with the different formulations.

Clinical relevance

The mean estimated difference in PPD reduction between probiotics and placebo was not statistically significant and of limited clinical relevance (difference < 0.5 mm). Moreover, two groups published four out of the five RCTs included each of them using a different probiotic formulation. Preparations containing Lactobacillus reuteri were the only ones to demonstrate improved PPD reductions.

Given that probiotics embrace a broad range of micro‐organisms and types of preparations, combining such data within the same meta‐analysis poses an interpretational challenge.

Balance of benefits and harms

All formulations appeared to be safe and patients did not report adverse effects.

Economic considerations

There is an additional cost associated with the use of probiotics that is borne by the patient.

Applicability

All studies were conducted in two countries, and no conclusions can be drawn on the effectiveness of probiotics as adjuncts to subgingival instrumentation.

Intervention

Sub‐antimicrobial dose doxycycline (up to 40 mg a day) is a systemic drug employed specifically for its anti‐inflammatory as opposed to its antimicrobial properties. The formulation offers anti‐collagenolytic activity, which may have utility in reducing connective tissue breakdown and augmenting healing responses following subgingival instrumentation in periodontitis patients.

Available evidence

Eight placebo‐controlled RCTs (14 publications, n = 610) reported on the systemic use of a sub‐antimicrobial dose doxycycline (SDD) (up to 40 mg a day) in combination with subgingival instrumentation. Meta‐analysis on PPD reduction (primary outcome) at 6 months post‐subgingival instrumentation was performed in five RCTs (n = 484).

Risk of bias

One study was considered to be at high risk of bias and the remaining studies presented some concerns in certain domains. Of the five studies included in meta‐analysis, three declared industrial sponsorship, one was sponsored by the academic institution, and the fifth did not declare funding.

Consistency

The systematic review included data from eight RCTs, but meta‐analysis was performed in five RCTs that stratified pockets into moderate (4–6 mm) versus deep (≥7 mm). The findings were consistent in all studies. The I ² statistic was 0% (95% CI [0%; 64.1%]) for both moderate and deep pockets. Two out of five RCTs included did not report a power calculation. The strict experimental protocols employed by the five studies included in the meta‐analysis limits the generalizability of the outcomes.

Clinical relevance of outcomes and effect size

Additional PPD reductions reported following the use of SDD were 0.22 mm at 6 months and 0.3 mm at 9 months in moderate depth pockets. The mean prediction interval ranged from 0.06 mm to 0.38 mm at 6 months and from 0.15 mm to 0.45 mm at 9 months. At deep sites, the additional PPD reductions were more clinically relevant, with 0.68 mm mean additional PPD reductions at 6 months and 0.62 mm at 9 months. The mean prediction interval ranged from 0.34 mm to 1.02 mm at 6 months and from 0.28 mm to 0.96 mm at 9 months. Percentage of pocket closure was not reported.

Balance of benefits and harm

Most studies in the SDD category did not report any serious adverse events or patient dropouts that were directly attributed to the medication. However, it is known that doxycycline may lead to elevations in liver enzymes, which was evident for some patients in the results of one RCT included in the systematic review (Caton et al., 2000, 2001). The sustainability of the benefits or adverse events beyond the study period is unknown.

Ethical considerations

Current health policies on antibiotic stewardship and related public health concerns surrounding increasing antibiotic resistance need to be taken into account. The systemic effects of a drug taken over a 6‐ to 9‐month period during the initial phase of subgingival instrumentation require careful consideration when extrapolating outcomes from controlled research trials into general clinical practice.

Legal considerations

SDD is not approved or available in some European countries.

Economic considerations

There is a cost associated with the use of SDD that is borne by the patient.

Applicability

SSD is mainly effective in deep sites (≥7 mm), although SDD is used as a systemic rather than a site‐specific treatment. The clinical significance in deep sites (0.68 mm at 6 months and 0.62 mm at 9 months) is small, given that re‐treatment with non‐surgical root debridement might yield additional PPD reductions, and local drug delivery systems may yield similar effect sizes. Moreover, the five studies that did stratify results based upon pocket depth did not present an a priori statistical plan powered to stratify results in that manner.

Intervention

Bisphosphonates (BPs) are a class of antiresorptive agents that act mainly by inhibiting osteoclast activity. BPs can also directly inhibit host degradative enzymes like matrix metalloproteinases released by osteoclasts and other cells of the periodontium. There is also evidence that BPs reduce osteoblast apoptosis, thus increasing bone density as an overall therapeutic outcome. It is therefore rational to speculate that BPs may benefit the management of inflammation‐mediated alveolar bone resorption in periodontitis patients (Badran, Kraehenmann, Guicheux, & Soueidan, 2009).

Available evidence

Seven placebo‐controlled RCTs (n = 348), all from the same research group, on local delivery of 1% alendronate gel (six studies) and 0.5% zolendronate gel (one study) in infrabony or furcation Class II defects were identified.

A meta‐analysis on PPD reduction at 6 months in five RCTs (n = 228) using either single or multiple sites per patient in infrabony defects was undertaken. Two placebo‐controlled RCTs (n = 90) evaluated systemic administration of BPs (alendronate and risedronate).

Risk of bias

Of the nine studies included, two were at high risk of bias and seven presented some concerns in at least one of the domains of the risk of bias assessment tool. One study was underpowered. All studies on local BPs were published by the same research group. While pharmaceutical companies provided bisphosphonates for local application in the included studies, the level of involvement of industry in the analysis and interpretation of the results is unclear.

Consistency

Nine RCTs were available, two involving systemic administration of BPs. No meta‐analysis was therefore undertaken for systemic BPs. Out of the seven RCTs involving local application of BPs, five were on infrabony defects (four employed 1% Alendronate gel and one study used 0.5% Zolendronate gel), while two were undertaken on furcation Class II defects (all using 1% Alendronate gel). A meta‐analysis of five studies using single or multiple sites per patient demonstrated a significant benefit in terms of PPD reduction of 2.15 mm (95% CI [1.75; 2.54]) after 6 months from non‐surgical periodontal therapy in infrabony defects, with a low level of heterogeneity (I ² = 47.3%).

Clinical relevance

The results of the two studies on systemic BPs were poorly comparable as they were undertaken in different populations and involved different confounding factors (e.g. smoking).

Although the mean estimates suggested adjunctive benefits from adjunctive use of BP gels, the combined use of studies considering single and multiple sites per patient in the meta‐analysis should be taken into consideration.

Balance of benefits and harm

Both systemic and local BPs were well‐tolerated in the studies reported in the systematic review and were not associated with severe adverse reactions.

Economic considerations

There is an additional cost associated with the use of bisphosphonates that is borne by the patient.

Ethical and legal considerations

The balance of recognized potential severe risks (e.g. osteochemonecrosis of the jaws) versus benefits resulted in a consensus that systemic administration of BPs should not be recommended in the clinical management of periodontal bone loss. It is important to note that BP gel formulations are “off‐label” and an approved formulation with appropriate quality control (GMP) and patient safety validation is not available.

Applicability

The same research group/centre published all data on locally delivered BPs; therefore, the generalizability of the results requires substantiating in future larger (multicentre) RCTs, with multilevel analyses accounting for potential confounding factors (e.g. medical history, smoking history).

Intervention

Periodontitis is an inflammatory disease in which altered immune‐inflammatory responses to a dysbiotic biofilm drives connective tissue destruction and bone loss. It is reasonable therefore that non‐steroid anti‐inflammatory drugs (NSAIDs), may be effective as adjunctive periodontal therapies.

Available evidence

Two placebo‐controlled RCTs (n = 88) on local application, one using 1% flurbiprofen toothpaste twice daily for 12 months and a second using subgingival daily irrigation with 200 ml buffered 0.3% acetylsalicylic acid, were identified. Two placebo‐controlled RCTs (n = 133) on systemic applications, one RCT using systemic celecoxib (200 mg daily 6 months) and another using a cyclical regime of diclofenac potassium (50 mg 2‐months, then 2 months off, then 2 months on), were included. All studies reported on PPD reduction at 6 months. No meta‐analysis was performed due to the limited number of studies identified and their heterogeneity.

Risk of bias

Two out of four studies were considered at high risk of bias. All studies on NSAIDs either did not provide information on sample size calculation or were underpowered. All studies declared industry funding.

Consistency

It was not possible to undertake a meta‐analysis of local or systemic NSAID administration as an adjunct to subgingival instrumentation because the studies were heterogeneous (not comparable) in terms of the medication employed and the modality of administration.

Clinical relevance

Local NSAIDs did not enhance the clinical outcomes of subgingival instrumentation. Systemic NSAIDs exhibited limited clinical benefits, but their heterogeneity did not permit the drawing of clinically meaningful conclusions.

Balance of benefits and harm

No serious adverse events were reported.

Ethical considerations

Long‐term use of systemic NSAIDs carries a well‐known risk of unwanted side effects, which raises concerns over their use as adjuncts to subgingival instrumentation.

Economic considerations

There would be a cost to using NSAIDs which would ultimately transfer to the patient.

Applicability

We do not encourage everyday clinical use of systemic NSAIDs or to conduct future studies to test these medications in their current standard formulations or dosage regimes. No meaningful conclusions could be made regarding use of local NSAIDs. Based on the current limited evidence, local NSAIDs did not provide a clinical benefit.

Intervention

The recent discovery of pro‐resolving lipid mediators by Serhan and colleagues [reviewed by (Serhan, 2017)], some of which are produced by the metabolism of two major omega‐3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) to E‐ and D‐resolvins, respectively, raises the potential for essential dietary PUFAs as adjunctive host‐modulating therapeutics for non‐surgical periodontal treatment. However, few studies have investigated their efficacy in human trials.

Available evidence

Three placebo‐controlled RCTs (n = 160) with 6‐month administration of omega‐3 PUFAs. Heterogeneity in study designs precluded a meta‐analysis. One RCT investigated low dose omega‐3 PUFAs (6.25 mg eicosapentaenoic acid ‐EPA and 19.9mg docosahexaenoic acid ‐DHA) twice daily for 6 months; a second study employed high dose omega‐3 PUFAs (3 g) in combination with 81 mg aspirin daily for 6 months; and a third study used 1 g omega‐3 PUFAs twice daily for 6 months. All studies provided PPD reduction data at 6 months post‐subgingival instrumentation. No meta‐analysis was performed due to the limited number of studies identified and their heterogeneity.

Risk of bias

One out of three studies was considered to be at high risk of bias. One study reported industry support, one was supported by a University, and one did not disclose the funding source.

Consistency

No meta‐analysis could be performed due to the low number of available studies and study heterogeneity in terms of proposed regime and formulation.

Clinical relevance

Since the three RCTs used different doses and preparations of omega‐3 PUFAs and one out of three studies combined omega‐3 with 81 mg aspirin, it was not possible to draw clinically meaningful conclusions from the data.

Balance of benefits and harm

No adverse events were associated to the use of omega‐3 PUFAs, and they are essentially a relatively safe dietary supplement.

Economic considerations

There would be a cost to using omega‐3 PUFAs which would ultimately transfer to the patient.

Applicability

There is insufficient data to support or refute the use of omega‐3 PUFAs, either as a monotherapy or as a combined therapeutic adjunct to subgingival instrumentation. The combination of omega‐3 fatty acids and low‐dose aspirin also warrants further assessment of its use as an adjunct in the management of periodontitis.

Intervention

Metformin is a second‐generation biguanide used to manage type 2 diabetes mellitus. There is evidence suggesting that metformin decreases inflammation and oxidative stress and may also have an osteogenic effect by increasing the proliferation of osteoblasts and reducing osteoclast activity (Araujo et al., 2017). It is therefore plausible that this medication may be beneficial in treating a chronic inflammatory disease like periodontitis.

Available evidence

Six placebo‐controlled RCTs (n = 313) from the same research group investigated locally delivered 1% metformin gel as an adjunct to subgingival instrumentation. All studies reported on PPD reduction at 6 months post‐subgingival instrumentation, and a meta‐analysis was undertaken combining the six RCTs.

Risk of bias

Four out of six studies presented some concerns of risk of bias in most of the domains. All studies were published by the same research group. While pharmaceutical companies provided metformin, the level of involvement of industry in the analysis and interpretation of the results is unclear.

Consistency

Meta‐analysis of six studies (four considering single sites per patient and two considering multiple sites per patient) indicated that 1% metformin gel as adjunct to subgingival instrumentation led to an improved PPD reduction of 2.07 mm (95% CI [1.83; 2.31]) at 6 months. Heterogeneity between the studies was low (I ² = 43%).

Clinical relevance

All studies reported a benefit in terms of PPD reduction when 1% metformin gel was used as an adjunct to subgingival instrumentation. However, studies using single and multiple sites per patients were combined.

Balance of benefits and harms

All studies included in the review reported that patients tolerated local metformin gel well, without any complications, adverse reactions/side‐effects, or symptoms of hypersensitivity.

Ethical and legal considerations

The metformin formulation included in the systematic review is “off‐label” and an approved formulation with appropriate quality control (GMP) and patient safety validation is not available.

Economic considerations

There is an additional cost associated with the use of metformin that is borne by the patient.

Applicability

The same research group published all data on local metformin; therefore, the generalizability of the results needs to be confirmed in future larger (multicentre) RCTs, with multi‐level analyses accounting for potential confounding factors (e.g. medical history, smoking history).

Intervention

In order to control gingival inflammation during periodontal therapy, the adjunctive use of some agents has been proposed. Chlorhexidine mouth rinses have been frequently tested in this indication and frequently used in different clinical settings.

Available evidence

In the systematic reviews of the present European Workshop, the role of antiseptics in active periodontal therapy has not been directly addressed. However, some evidence is available based on studies on the role of chlorhexidine use after subgingival instrumentation (da Costa et al., 2017).

In addition, other factors should be considered:

• It is unclear whether this should be a general recommendation for initial therapy.

• It may be necessary to optimize mechanical plaque control before considering adjunctive chlorhexidine as an adjunct to subgingival instrumentation.

• Specific considerations can be made when used in conjunction with full‐mouth disinfection approaches and/or with systemic antimicrobials.

• The medical status of the patient.

• Adverse effects (staining) and economical costs should be considered.

Intervention

There is insufficient evidence on the benefits of locally administered sustained‐release antiseptics as an adjunct to subgingival debridement in patients with periodontitis.

Available evidence

The systematic review (Herrera et al., 2020) revealed results from studies on products containing chlorhexidine (Periochip n = 9, Chlosite n = 2). One product (Periochip) demonstrated statistically significantly greater PPD reduction following single or multiple applications as an adjunct to subgingival debridement on short‐term follow‐up (6–9 months) (weighted mean difference (WMD) = 0.23, 95% CI [0.12; 0.34], p < .001 and significant heterogeneity). There are no long‐term data available. No significant differences were found regarding CAL. Data on BOP were insufficient and no data on pocket closure or on number needed to treat (NNT) were provided.

Risk of bias

High risk of bias and heterogeneity among studies.

Clinical relevance and effect size

Effect size estimated for all PPD categories indicates an increased effect of about 10% in PPD reduction.

Balance of benefit and harm

No increase in adverse effects or differences in patient‐reported outcome measures (PROMs) were observed.

Economic considerations

The cost for the product and the limited availability of products in European countries need to be considered.

Available evidence

Of the products available on the European market, the systematic review (Herrera et al., 2020) revealed statistically significantly improved PPD reduction of locally applied antibiotics as an adjunct to subgingival debridement on short‐term follow‐up (6–9 months) for Atridox (two studies, WMD = 0.80; 95% CI [0.08; 1.52]; p = .028), Ligosan (three studies, WMD = 0.52; 95% CI [0.28; 0.77]; p < .001) and Arestin (six studies, WMD = 0.28; 95% CI [0.20; 0.36]; p < .001). No significant adjunctive long‐term effect was evident. Statistically significantly improved CAL change for products used as an adjunct to subgingival debridement on short‐term follow‐up (6–9 months) was identified for Ligosan (n = 3, WMD = 0.41, 95% CI [0.06; 0.75]; p = .020) and Arestin (n = 4, WMD = 0.52; 95% CI [0.15; 0.88]; p = .019). Long‐term data did not show significant improvement of CAL for any product. Data on BOP and pocket closure were insufficient. No information on NNT was provided. Estimated effect size indicates an increased effect of 10%–30% in PPD reduction.

Risk of bias

High risk of bias and heterogeneity in the majority of studies.

Balance of benefit and harm

No increase in adverse effects or differences in PROMs were observed. Harm versus benefit considerations on the use of antibiotics need to be considered.

Economic considerations

High economic costs and limited availability of products in European countries need to be considered.

Available evidence

While the results from the meta‐analysis (Teughels et al., 2020) revealed a statistically significantly improved outcome for systemically administrated antibiotics as an adjunct to subgingival debridement, the effect was confined to a limited group of antibiotics. A significantly improved PPD reduction at the 6‐month follow‐up was observed for metronidazole (MET) and amoxicillin (AMOX) (n = 8; WMD = 0.43, 95% CI [0.36; 0.51]). Analysis of 12‐month data revealed a significant adjunctive effect for MET + AMOX (n = 7; WMD = 0.54, 95% CI [0.33; 0.74]) and MET (n = 2; WMD = 0.26, 95% CI [0.13; 0.38]). The adjunctive use of MET + AMOX and MET resulted in a statistically significant additional percentage of pocket closure at 6 and 12 months. Statistically significantly greater CAL gain and BOP reduction for MET + AMOX at 6 and 12 months. The adjunctive effect of MET + AMOX on PPD reduction and CAL gain was more pronounced in initially deep than moderately deep pockets. There are no relevant data on the long‐term (>12 months) effect of using systemic antibiotics as an adjunct to subgingival debridement. NNT was not assessed.

Risk of bias

Low risk of bias and low heterogeneity among studies.

Consistency

High consistency of results.

Clinical relevance and effect size

Effect size estimation on PPD reduction as opposed to subgingival debridement alone indicates an increased effect of about 40%–50%.

Balance of benefit and harm

While the MET + AMOX combination had the most pronounced effects on the clinical outcomes among the different types of systemic antimicrobial therapy, the regimen was also associated with the highest frequency of side effects. Global concerns regarding the overuse of antibiotics and the development of antibiotic resistance must be considered. Benefit versus harm analysis includes considerations on the overall use of antibiotics for the individual patient and public health. Systemic antibiotic regimens have shown long lasting impact on the faecal microbiome, including an increase in genes associated with antimicrobial resistance.

Applicability

Due to concerns to patient's health and the impact of systemic antibiotic use to public health, its routine use as adjunct to subgingival debridement in patients with periodontitis is not recommended. Based on the available evidence, however, its adjunctive use may be considered for special patient categories (e.g. generalized periodontitis Stage III in young adults).

Available evidence

Statistically significantly greater PPD reduction was observed in access flaps (AF) than in subgingival debridement at 1 year. The difference was more pronounced at initially deep sites (PPD ≥ 6 mm) (four studies, WMD = 0.67, 95% CI [0.37; 0.97], at 1 year; WMD = 0.39; 95% CI [0.09; 0.70] at >1 year). The relative effect was 27.5%. These differences in PPD reduction also occurred in pockets associated with infrabony defects (four studies; WMD = 0.49, 95% CI [0.11; 0.86]). No statistically significant differences in CAL gain at initially deep pockets were observed between procedures. However, CAL gain was significantly greater in the subgingival debridement group at initially moderately deep pockets, and AF resulted in statistically significantly more attachment loss at sites with initial PPD ≤ 4 mm. Statistically significantly higher percentage of shallow pockets was achieved with AF than with subgingival debridement (three studies, WMD = 11.6%, 95% CI [6.76; 16.5]). The need of re‐treatment (four studies) was 8%–29% in the subgingival debridement group and 0%–14% in the AF. There were no statistically significant differences in PROMs between the interventions.

Available evidence

Out of three available studies comparing MWF with OFD, only one showed statistically significantly greater PPD reduction for MWF than OFD. There were no statistically significant differences in % PPD reduction in deep infrabony pockets between papilla preservation flap (single flap approach) and conventional flaps (one study). Two studies comparing minimally invasive surgery with conventional surgery did not demonstrate a significant added value in PPD reduction or CAL gain.

Available evidence

Resective periodontal surgery attained statistically significantly higher PPD reduction than access flaps at 6 months (WMD = 0.59 mm; 95% CI [0.06–1.12]) and one year (WMD = 0.47 mm; 95% CI [0.24; 0.7]). For pockets 4–6 mm, differences were statistically significant at 1 year (WMD = 0.34 mm; 95% CI [0.19; 0.48]), while pockets 7 mm or deeper showed greater difference between the groups (WMD = 0.76 mm; CI [0.35; 1.17]). The differences were lost with time (3‐ and 5‐year follow‐up). There were no differences in CAL gains between the surgical modalities in the long term (3–5 years). Post‐operative recession was statistically significantly greater following resective surgery than access flaps at 1‐year post‐op (two studies). No differences reported at 5‐year follow‐up (one study). No differences in recession over time in initially shallow pockets between the two modalities.

Risk of bias

High risk of bias, scarcity of quantitative data (only 4 RCTs).

Clinical relevance and effect size

The paucity of the data on percentage of shallow pockets or incidence of re‐treatment prevents assessments of the clinical relevance of the differences.

Balance of benefit and harm

Data on PROMs, the percentage of residual pockets or the need of re‐treatment were not reported in any of the studies.

Intervention

Advanced periodontal surgery (regenerative and furcation management) is beyond the scope and competence of education in general dental practice (Sanz & Meyle, 2010). Dental curricula include knowledge and familiarity with the approach but are not designed to provide competence to conduct such treatment: Additional specific training is required and is available through continuing professional development and periodontal learned societies in most countries. Post‐graduate periodontal education, on the other hand, is specifically designed to provide competence and proficiency towards the resolution of such complex problems (Sanz, van der Velden, van Steenberghe, & Baehni, 2006; Van der Velden & Sanz, 2010).

Intervention

Dental services are organized differently in various countries. Some are structured in both primary care and specialist care (usually delivered by referral to dental hospitals or specialist practices/centres); in other countries, dental services are based on a single level of care and interested general practitioners acquire broader periodontal skills through continuing professional development. Optimal management of Stage III and Stage IV periodontitis remains limited in most health systems with significant inequalities in availability and access to advanced/specialist periodontal care. There is an urgent need to improve patient access to the appropriate level of care given the high burden and costs associated with the sequelae of unmanaged severe (stages III and IV) periodontitis.

Intervention

Proof‐of‐principle studies conducted in the 1970s have pointed to the negative effects (clinical attachment loss) of performing periodontal surgery in subjects with inadequate plaque control (Nyman, Lindhe, & Rosling, 1977; Rosling, Nyman, Lindhe, & Jern, 1976). Multiple RCTs on surgical periodontal intervention have shown a dose‐dependent effect of plaque control on healing outcomes. Similar data have been reported after implant surgery (van Steenberghe et al., 1990). The level of self‐performed oral hygiene is clinically assessed using a plaque control record [for an example, see (O'Leary, Drake, & Naylor, 1972)]. Plaque scores smaller than 20%–25% have been consistently associated with better surgical outcomes (see Step 1 and SPC clinical recommendations for detailed discussions on how to facilitate achieving stringent levels of self‐performed oral hygiene).

Intervention

See previous sections. An algorithm for clinical decision‐making in the treatment by regenerative surgical therapy of intrabony defects and residual pockets is depicted in Figure 1.

Available evidence

The evidence base includes 22 RCTs with 1,000 patients. The quality of the evidence was rated as high.

Risk of bias

Study quality assessment identified four studies at low risk of bias and 15 studies at unclear risk of bias.

Consistency

Regenerative surgical therapy resulted in improved clinical outcomes (shallower pockets and higher CAL gain) compared with open flap debridement in the majority of studies. No indication of publication bias was observed. Moderate to substantial heterogeneity in the size of the adjunctive effect was observed. This could be partly explained by the use of specific biomaterials or flap designs.

Clinical relevance and effect size

The mean adjunctive benefit reported was 1.34 mm (95% CI [0.95; 1.73]) in CAL gain and 1.20 mm (95% CI [0.85; 1.55]) in pocket depth reduction. This represented an 80% (95% CI [60%; 100%]) improvement compared to the controls. A mean difference of this magnitude is deemed clinically relevant as it has the potential of decreasing risk of tooth loss. Observational and experimental studies reporting on tooth survival for a period of 3–20 years show improved tooth retention with periodontal regeneration in teeth under regular supportive periodontal therapy (28 RCTs summarized in unpublished data).

Balance of benefit and harm

No serious adverse event was reported in any of the studies included in the systematic review. The adverse events associated with regenerative therapy included local adverse events (wound failure) and post‐operative morbidity. No specific harm has been reported after regenerative surgery. Potential risk for disease transmission from well‐documented human‐derived or animal‐derived regenerative biomaterials is considered extremely low.

Ethical considerations

The perception that regenerative treatment of deep intrabony defects results in better outcomes than access flap is commonly held in the research and clinical community. Therefore, maximum tissue preservation flap with the application of documented regenerative biomaterials should be the standard of care. This perception is supported by the observation that only 22 of 79 RCTs included in the systematic review used access flap as the control and the majority of the body of evidence compared different regenerative techniques/biomaterials.

Regulatory consideration

It is important to emphasise that only few classes of regenerative materials are registered in Europe. In each class, only few materials satisfy the evidence base criteria set forth by these guidelines and the considerations should not be applied to materials that have not been adequately tested. Implementation of the new EU medical device regulations will prove useful.

Economic considerations

Regenerative surgery is more expensive than access flap surgery but cheaper than tooth replacement necessary as a consequence of tooth loss. In the absence of health‐economic data in RCTs included in the review, a pilot study has indicated that the initial increase in cost of regeneration is associated with lower cost of managing recurrence over a 20‐year period (Cortellini, Buti, Pini Prato, & Tonetti, 2017).

Patient preferences

No data are available about patient preference or acceptability. Religious issues may be present for segments of the population since some of the regenerative materials are of porcine or bovine origin. While the use for medical reasons is generally acceptable and has been approved by religious leaders, the sensitivity of individual subjects may pose a barrier.

Intervention

See previous sections.

Available evidence

The evidence base includes 20 RCTs with 972 patients. The quality of the evidence was considered to be high.

Risk of bias

Study quality assessment identified four studies at low risk of bias and 15 studies at unclear risk of bias.

Consistency

Regenerative surgical therapy with a variety of biomaterials resulted in improved clinical outcomes compared with open flap debridement in the majority of studies. No indication of publication bias was observed. Moderate to substantial heterogeneity in the size of the adjunctive effect was observed.

Clinical relevance and effect size

The mean adjunctive benefit in term of CAL gain was 1.27 mm (95% CI [0.79; 1.74], equivalent to a 77% improvement) for EMD and 1.43 mm (95% CI [0.76; 2.22], equivalent to an 86% improvement) for guided tissue regeneration (GTR) compared with OFD. The combination of membrane with bone‐derived graft resulted in higher CAL gain of 1.5 mm (95% CI [0.66; 2.34], equivalent to a 90% improvement) compared with OFD. The comparison between EMD versus GTR resulted in no statistically significant difference in CAL gain. The choice of biomaterial or possible combinations should be based on defect configuration.

Intervention

See previous sections.

Available evidence

The evidence base includes two systematic reviews.

Risk of bias

Study quality assessment identified five studies at low risk of bias and 15 studies at unclear risk of bias.

Consistency

No conclusion can be drawn.

Clinical relevance and effect size

Papilla preservation flaps have been shown to lead to increased CAL gain and PD reduction as well as reduced post‐surgical recession compared with OFD.

Balance of benefit and harm

No serious adverse event has been reported after application of papilla preservation flaps in regenerative periodontal surgery performed by adequately trained clinicians. The added complexity of the surgery requires additional training.

Applicability

Anatomical considerations related to the width of the interdental space advise on the choice of the preferred flap design to access the interdental area (Cortellini, Prato, & Tonetti, 1995, 1999). Location and configuration of the intrabony defect advise on the possibility to (a) minimize flap extension (Cortellini & Tonetti, 2007; Harrel, 1999), and (b) raise a single flap or the need to fully elevate the interdental papilla (Cortellini & Tonetti, 2009; Trombelli, Farina, Franceschetti, & Calura, 2009).

Intervention

See previous sections. An algorithm for clinical decision‐making in the treatment by periodontal surgery of molars with furcation involvement (Class I, Class II) and residual pockets is depicted in Figure 2.

Available evidence

The evidence base includes 20 RTCs with 575 patients (Class II buccal/lingual mandibular and maxillary buccal furcation involvement) and seven observational studies with 665 patients (Class II interproximal and Class III). Previous systematic reviews have addressed the clinical performance of periodontal therapy of teeth with furcation involvement (Huynh‐Ba et al., 2009; Nibali et al., 2016).

Risk of bias

High quality of evidence of RCTs. Low quality of evidence for observational studies.

Consistency

Following treatment, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

Clinical relevance and effect size

Following treatment, reasonable survival rates were observed over 4–30.8 years. Overall, the observed tooth survival rates were better in Class II furcation involvement than Class III.

Balance of benefit and harm

We did not identify data about harm directly related to procedures.

Economic considerations

Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost‐effective than their extraction and replacement with an implant supported fixed partial denture (Schwendicke, Graetz, Stolpe, & Dorfer, 2014). A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal (Schwendicke, Plaumann, Stolpe, Dorfer, & Graetz, 2016).

Patient preferences

There is a strong patient preference for tooth retention (IQWiG, 2016).

Applicability

The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver surgical furcation treatment in the different European health systems.

Intervention

See previous sections.

Available evidence

The evidence base includes 17 RCTs with 493 patients. The quality of the evidence for the statement was assessed according to GRADE and considered to be high. In the systematic review underlying this recommendation (Jepsen et al., 2019), a standard meta‐analysis grouping all regenerative techniques versus OFD was performed altogether with ancillary analysis. Results indicated that regenerative therapies had a significant benefit over OFD in terms of both primary and surrogate outcomes.

Risk of bias

Study quality assessment identified an unclear risk of bias for the majority of the studies. Bearing in mind that six papers failed to disclose support and seven papers reported industry funding for the research.

Consistency

Regenerative treatment consistently demonstrated added benefits (in terms of furcation improvement, horizontal bone gain, horizontal and vertical attachment gain, pocket reduction) in comparison with OFD.

Clinical relevance and effect size

The mean adjunctive benefit of a regenerative treatment is clinically relevant (1.3 mm vertical CAL and greater PPD reduction), and the effect size is significant as furcation improvement showed an odds ratio (OR) of 21 (Bayesian credible interval 5.8–69.4) in favour of regenerative techniques.

Balance of benefit and harm

The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

Ethical considerations

The perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction (and replacement) or open flap debridement.

Regulatory consideration

All the studies reported FDA‐ or CE‐approved devices.

Economic considerations

Regenerative surgery has additional costs, which appear to be justified by the added benefits (furcation improvements).

Patient preferences

Minimal data are available.

Applicability

Teeth presenting with favourable patient, tooth and defect‐related conditions.

Intervention

See previous sections.

Available evidence

The evidence base includes three RCTs with 82 patients (Garrett et al., 1997; Hugoson et al., 1995; de Santana, Gusman, & Van Dyke, 1999). The quality of the evidence for the statement was assessed according to GRADE and considered to be moderate. Of these studies only one (de Santana et al., 1999) had a clear comparison towards OFD indicating an added benefit.

Risk of bias

Study quality assessment identified an unclear/high risk of bias.

Consistency

Regenerative treatment demonstrated added benefits.

Clinical relevance and effect size

It cannot be extrapolated.

Balance of benefit and harm

The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

Ethical considerations

The expert perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction or open flap debridement.

Regulatory consideration

All the studies reported FDA‐ or CE‐approved devices.

Economic considerations

Regenerative surgery has additional costs which appear to be justified by the added benefits (furcation improvements).

Patient preferences

No data are reported.

Applicability

Teeth presenting with favourable patient, tooth and defect‐related conditions.

Intervention

See previous sections.

Available evidence

The evidence base includes 17 RCTs with 493 patients for mandibular Class II and three RCTs with 82 patients for maxillary buccal Class II. The quality of the evidence for the statement was assessed according to GRADE and considered to be high/moderate. In the systematic review underlying this recommendation (Jepsen et al., 2019), a Bayesian network meta‐analysis was performed to assess which treatment modalities demonstrated the highest likelihood of success. For the outcome such as HBL, the highest‐ranked groups were bone replacement graft, GTR with a bone replacement graft or enamel matrix derivative.

Risk of bias

Study quality assessment identified an unclear risk of bias for the majority of the studies. There is a mix of researcher and industry‐initiated studies.

Consistency

The procedures with the highest ranking for horizontal bone gain are bone‐replacement graft, bone‐replacement graft with resorbable membranes or enamel matrix derivative.

Clinical relevance and effect size

It cannot be extrapolated among the therapies.

Balance of benefit and harm

The benefit of regenerative therapies to promote tooth retention outweighs the adverse events which consist mainly of local wound failure.

Ethical considerations

The perception is that regenerative therapies to promote tooth retention are preferred over tooth extraction and open flap debridement.

Regulatory consideration

All the studies reported FDA‐ or CE‐approved devices.

Economic considerations

Regenerative surgery has additional costs, which appear to be justified by the added benefits (furcation improvements).

Patient preferences

Enamel matrix derivative showed less postoperative swelling and pain than non‐resorbable membranes.

Applicability

Teeth presenting with favourable patient, tooth and defect‐related conditions.

Intervention

See previous sections.

Available evidence

Six observational studies with 633 patients (Class II interproximal).

Risk of bias

Low quality of evidence for observational studies.

Consistency

Following non‐regenerative treatment of maxillary interproximal Class II furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

Clinical relevance and effect size

Following non‐regenerative treatment of maxillary interproximal Class II furcation involvement, reasonable survival rates were observed over 4–30.8 years.

Balance of benefit and harm

We did not identify data about harm directly related to procedures. Regarding tooth survival, a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

Economic considerations

Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost‐effective than their extraction and replacement with an implant supported fixed partial denture (Schwendicke et al., 2014). A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal (Schwendicke et al., 2016).

Patient preferences

There is a strong patient preference for tooth retention (IQWiG, 2016).

Applicability

The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver surgical furcation treatment in the different European health systems.

Intervention

See previous sections.

Available evidence

Six observational studies with 633 patients.

Risk of bias

Low quality of evidence for observational studies.

Consistency

Following treatment of maxillary Class III furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

Clinical relevance and effect size

Following treatment of maxillary Class III furcation involvement, reasonable survival rates were observed over 4–30.8 years.

Balance of benefit and harm

We did not identify data about harm directly related to procedures. Regarding tooth survival, a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

Economic considerations

Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost‐effective than their extraction and replacement with an implant supported fixed partial denture (Schwendicke et al., 2014). A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal (Schwendicke et al., 2016).

Patient preferences

There is a strong patient preference for tooth retention (IQWiG, 2016).

Applicability

The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver resective treatment in the different European health systems.

Intervention

See previous sections.

Available evidence

Seven observational studies with 665 patients (with mandibular class III furcation).

Risk of bias

Low quality of evidence for observational studies.

Consistency

Following treatment mandibular Class III furcation involvement, moderate to substantial heterogeneity in the size of the effect (wide ranges of tooth survival) was observed. The reasons cannot be determined from the existing data.

Clinical relevance and effect size

Following treatment of mandibular Class III furcation involvement, reasonable survival rates were observed over 4–30.8 years.

Balance of benefit and harm

We did not identify data about harm directly related to procedures. Regarding tooth survival a benefit of root amputation/resection, root separation or tunnelling compared to SRP or OFD cannot be currently stated. For the individual choice of procedure, however, the clinician should consider criteria beyond class of furcation involvement (e.g. bone loss, jaw).

Economic considerations

Simulations based on the German health system have indicated that tooth retention after complex periodontal therapy of teeth with furcation involvement is more cost‐effective than their extraction and replacement with an implant supported fixed partial denture (Schwendicke et al., 2014). A study assessing the actual cost of retention of molars in the same health system showed that cost for retaining periodontally compromised molars were minimal (Schwendicke et al., 2016).

Patient preferences

There is a strong patient preference for tooth retention (IQWiG, 2016).

Applicability

The guideline can be applied since it is independent of availability of materials and a segment of the dental workforce has been trained or can be trained to deliver resective treatment in the different European health systems.

Intervention

Although not addressed directly in the systematic reviews underlying this guideline, different evidence supports the concept of defined intervals to perform SPC visit every 3–4 months are recommended in studies selected by Trombelli et al. (2020).

• SPC every 3 months may be sufficient to control periodontitis progression after periodontal surgery (Polak et al., 2020).

• In addition, the conclusions of the 2014 European Workshop on Prevention, based on the review by Trombelli et al. (2015), concluded that the recommended interval ranges 2–4 times per year and that it could be optimized if it is tailored according to patient's risk (Sanz et al., 2015).

• A recent study (Ramseier et al., 2019), over 883 patients, reflected on the importance of SPC and the factors involved in its success.

Intervention

Although not addressed directly in the systematic reviews underlying this guideline, different evidence supports the importance of complying with SPC visit, in which PMPR is performed:

• Greater rates of tooth loss and disease progression in patients with irregular compliance, versus patients with regular compliance (Costa et al., 2014).

• The conclusions of the 2014 European Workshop on Prevention, based on the review by Trombelli et al. (2015), concluded that compliance with the preventive professional intervention is crucial, based also on retrospective observational studies (Sanz et al., 2015).

Intervention

All surfaces exposed to the formation of intraoral biofilm have to be cleaned mechanically. Some of them will not be reached by toothbrushes even under optimized conditions. Interproximal cleaning therefore is essential in order to maintain interproximal gingival health, in particular for secondary prevention. It may be achieved using different devices, primarily inter‐dental brushes (IDB, which are not single‐tufted brushes), rubber/elastomeric cleaning sticks, wood sticks, oral irrigators and floss. However, all devices have the potential of side effects and their use has to be monitored not only with respect to efficacy but also with respect to early signs of trauma (e.g. onset of non‐carious cervical lesions).

Available evidence

Due to the scarcity of studies that met the inclusion criteria for each of the oral hygiene devices and the low certainty of the resultant evidence, no strong “evidence based” conclusion can be drawn concerning any specific oral hygiene device for patient self‐care in periodontal maintenance. The evidence that emerged from the search provided 16 papers reporting on 13 CCTs/RCTs, which included 17 comparisons. The differences of powered versus manual toothbrushes were evaluated in five comparisons, an interdental device was used as an adjunct to toothbrushing in five comparisons, and seven comparisons evaluated two different interdental devices. In total, the studies evaluated 607 patients.

Risk of bias

Study quality assessment identified one study at low risk of bias and 10 studies at high risk and two of an unclear risk of bias.

Consistency

The summary of findings table shows that the body of evidence is rather consistent.

Clinical relevance and effect size

Variable, depending on the comparisons established.

Balance of benefit and harm

The adverse events were not evaluated. There is a moderate risk of trauma due to the use of interdental cleaning devices, when not used properly. Therefore, individual instruction and adoption to the individual situation by professionals are crucial. In any case, the benefits overweigh the risks by far.

Economic considerations

A manual toothbrush is less expensive than a power toothbrush. Interdental brushes and oral irrigators are more expensive than dental floss, wood sticks and rubber and silicon interdental bristle cleaners.

Patient preferences

No data on patient preference arrive from the current review.

Applicability

The guideline can be applied to patients attending a periodontal maintenance program. There is an abundance of mechanical oral hygiene products available.

Intervention

See previous section.

Available evidence

Scarcity or a lack of evidence does not necessarily imply that products may not be effective. Dental care professionals in clinical practice should tailor the best oral hygiene devices and methods according to patients' skill levels and preferences because patient acceptance is crucial for sustained long‐term use (Steenackers, Vijt, Leroy, De Vree, & De Boever, 2001). Clinical evidence indicates that the efficacy of interdental brushes depends on the relation between the size of the brush and the size and shape of the interdental space. Interdental spaces underlay a high variety regarding size and morphology, and interdental brushes have to be selected specific to the individual interdental space. The number of devices has to be limited to a certain number with respect to the ability of the patient to cope with this diversity. To reach this goal, compromises have to be found to achieve the individual optimum.

Intervention

See previous sections.

Available evidence

Based on the evidence from the systematic reviews underlying this guideline, toothbrushing is effective in reducing levels of dental plaque (Van der Weijden & Slot, 2015). Toothbrushes vary in size, design and the length, hardness and arrangement of the bristles. Some manufacturers have claimed superiority in modifications such as bristle placement, length and stiffness. Powered toothbrushes with various mechanical motions and features are available. The evidence that emerged from the search provided eight papers describing five CCT/RCT comparisons. In total, the studies evaluated 216 patients. The quality of the evidence for the statement was assessed according to GRADE.

Risk of bias

Study quality assessment showed that all studies at high risk of bias.

Consistency

The summary of findings table shows that the body of evidence is rather consistent.

Clinical relevance and effect size

No differences could be found. The statistically established clinical evidence was calculated for one study and showed no clinically relevant effect size.

Balance of benefit and harm

The adverse events were not evaluated.

Economic considerations

A manual toothbrush is less expensive than a power toothbrush.

Patient preferences

No data on patient preference arrive from the current review.

Applicability

The guideline can be applied to patients attending a periodontal maintenance program. There is an abundance of toothbrushes available.

Intervention

See previous sections.

Available evidence

The underlying systematic review (Slot et al., 2020) found evidence for a significantly better cleaning effect of interdental cleaning devices as adjuncts to tooth brushing alone, and a significantly better cleaning effect of interdental brushes than of flossing. Both the descriptive analysis and the NMA indicate that IDBs are the first choice for periodontal maintenance patients. Seven comparisons from four RCTs (290 patients) were identified.

Risk of bias

Low to unclear.

Consistency

High.

Clinical relevance and effect size

Considered as clinically relevant.

Balance of benefit and harm

There is a moderate risk of trauma due to the use of interdental brushes, when not used properly. Therefore, individual instruction and adaptation to the individual situation by professionals are crucial. In any case, the benefits overweigh the risks by far.

Economic considerations

Not considered.

Patient preferences

There is clinical evidence supporting that patients with open interdental spaces prefer the use of interdental brushes over the use of dental floss.

Applicability

The guideline can be applied since appropriate quantities and varieties of interdental brushes are available on the European market.

Intervention

See previous sections.

Available evidence

The underlying systematic review (Slot et al., 2020) found evidence for a significantly better cleaning effect of interdental brushes than of flossing. Both the descriptive analysis and the NMA indicate that IDBs are the first choice for periodontal maintenance patients. Six comparisons from four RCTs (162 patients) were identified.

Risk of bias

High to unclear.

Consistency

High.

Clinical relevance and effect size

Considered as clinically relevant.

Balance of benefit and harm

There is a moderate risk of trauma due to the use of interdental brushes or flossing, when not used properly. Therefore, individual instruction and adaptation to the individual situation by professionals are crucial.

Economic considerations

Not considered.

Patient preferences

There is clinical evidence supporting that patients with open interdental spaces prefer the use of interdental brushes over the use of dental floss.

Applicability

The guideline can be applied since appropriate quantities and varieties of interdental brushes are available on the European market.

Intervention

Other interdental cleaning devices include rubber/elastomeric cleaning sticks, wood sticks, an oral irrigator or dental floss. Although there are very small and fine interdental brushes available on the market, it must be realized that not all interdental spaces are readily accessible with interdental brushes.

Available evidence

The underlying systematic review (Slot et al., 2020) identified three RCTs assessing the use of an adjunctive oral irrigator: two out of three studies demonstrated a significant effect of the irrigator on measures of gingival inflammation, but not on plaque scores. Rubber/elastomeric cleaning sticks are a relatively newly developed instruments with an increasing market share, and there only little evidence available on gingivitis patients that these devices are effective in reducing inflammation with no difference to interdental brushes (Abouassi et al., 2014; Hennequin‐Hoenderdos, van der Sluijs, van der Weijden, & Slot, 2018).

Risk of bias

High.

Consistency

Not evaluated.

Clinical relevance and effect size

Considered as moderate.

Balance of benefit and harm

Up to now no adverse effects have been reported.

Economic considerations

Not considered.

Patient preferences

Rubber/elastomeric cleaning sticks are highly accepted by patients as are oral irrigators.

Applicability

The guideline can be applied since appropriate quantities and varieties of interdental cleaning devices are available on the European market.

Intervention

In order to control gingival inflammation during periodontal maintenance, the adjunctive use of some agents has been proposed. These agents are mainly antiseptics agents, and can be delivered as dentifrices, as mouth rinses or both.

Available evidence

A systematic review (Figuero, Roldan, et al., 2019) was conducted, aiming to identify RCTs of, at least, 6 months of follow‐up, in treated periodontitis patients or in gingivitis patients, in which antiseptics, prebiotics, probiotics, anti‐inflammatory agents and antioxidant micronutrients were used as adjuncts to mechanical supragingival biofilm control. For antiseptic agents, the impact in the primary outcome, changes in gingival indices (analysed in 52 studies with 72 comparisons, including 5,376 test and 3,693 control patients), was statistically significant (p < .001) and the additional reduction, expressed as standardized weighted mean difference (S‐WMD), was −1.3 (95% CI [−1.489; −1.047]), with significant heterogeneity (p < .001). In treated periodontitis patients, analysed in 13 studies with 16 comparisons, including 1,125 test and 838 control patients, the impact was statistically significant (p < .001) and the additional reduction, expressed as S‐WMD, was −1.564 (95% CI [−2.197; −0.931]), with significant heterogeneity (p < .001). No conclusions could be made for other, non‐antiseptic, agents, since only one study was identified. Longer‐term studies in treated periodontitis patients are also relevant to assess periodontal stability. In the systematic review (Figuero, Roldan, et al., 2019), four long‐term studies (1.5–3 years) were identified, and no significant impact was observed for gingival indices. However, a 3‐year study demonstrated significant benefits in terms of frequency of deep periodontal pockets and in the number of sites that exhibited additional attachment and bone loss (Rosling et al., 1997).

Risk of bias

The great majority of these studies were industry‐funded, and there was a high risk of bias both within and across studies.

Consistency

Highly consistent across studies, 72 comparisons were included in the primary analysis.

Clinical relevance and effect size

Considered as clinically relevant.

Balance of benefit and harm

At least 31 studies assessed adverse events and PROMs and staining was the only relevant finding.

Economic considerations

The issue has not been addressed. For dentifrices, it may not be relevant, since a dentifrice has to be used combined with mechanical tooth brushing; for mouth rinse, the extra cost should be taken into consideration. It should also be noted that the evidence base contains studies using products that may no longer be available.

Patient preferences

Both dentifrices and mouth rinses are widely accepted by the population.

Applicability

Demonstrated with studies testing large groups from the general population. The adjunctive use of some agents has been proposed in those subjects who are not able to effectively remove supragingival biofilms by the sole use of mechanical procedures, but there is no direct evidence to support this statement.

Intervention

In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed. These agents are mainly antiseptics but some other agents, such as probiotics, prebiotics, anti‐inflammatory agents and antioxidant micronutrients, can be found in the literature. These products are mainly delivered as dentifrices or mouth rinses.

Available evidence

See also previous section. The adjunctive use of antiseptic agents has been proposed in those subjects who are not able to effectively remove supragingival biofilms by the sole use of mechanical procedures. Actually, the recommendations of the XI European Workshop in Periodontology (2014) highlighted that (Chapple et al., 2015) “For the treatment of gingivitis and where improvements in plaque control are required, adjunctive use of anti‐plaque chemical agents may be considered. In this scenario, mouth rinses may offer greater efficacy but require an additional action to the mechanical oral hygiene regime”. Recommending adjunctive antiseptics, to mechanical supragingival biofilm control, in a specific patient group, instead in the general population, is plausible, but there is no supporting evidence to defend it. Most studies assessing the adjunctive benefits of antiseptic formulations have been performed in general populations, with statistically significant benefits in plaque and gingival indices (Serrano, Escribano, Roldan, Martin, & Herrera, 2015). Therefore, different factors may be considered when deciding whether to recommend the use of an adjunctive agent to control gingival inflammation in patients in supportive periodontal care. It is noted that all patients need to use a toothbrush with a fluoride toothpaste. However, in those subjects who are not able to effectively control supragingival biofilms and/or gingival inflammation by the sole use of mechanical procedures, a decision is then made whether or not to utilise a toothpaste and/or a mouth rinse that contains a specific active agent (in addition to fluoride). This decision would follow a personalized approach to patient care and would need to consider two aspects:

• Local factors consider levels of gingival inflammation related to plaque level, accessibility for cleaning, anatomical factors, etc.

• General factors consider systemic factors, general health status, frailty, limited dexterity, etc., some of which may be more relevant in elderly patients.

The most frequent delivery format for antiseptic agents is dentifrices and mouth rinses, or even they can be delivered in both, simultaneously. The obvious benefit of dentifrice delivery is that no other delivery format is needed, and a dentifrice is going to be used anyway. Mouth rinse delivery offers a better distribution around the mouth (Serrano et al., 2015) and better pharmacokinetic properties (Cummins & Creeth, 1992). Some evidence suggests that the adjunctive use of mouth rinses may provide better outcomes than that of dentifrices. However, the evidence is conflictive and significant differences were only observed for the secondary outcome (Figuero, Roldan, et al., 2019). In addition, direct comparisons between similar agents/formulations, delivered either as dentifrice or mouth rinse, are not available.

The decision to select a specific toothpaste or a mouth rinse should be also based on a combination of factors:

• Patient preferences including cost, taste, etc.

• Unwanted effects including staining, burning sensation during use, etc.

• Potential negative impacts on beneficial aspects of the oral microbiome highlighted in recent evidence (e.g. impact on nitric oxide pathway) (Bescos et al., 2020).

• Potential negative impacts on blood pressure: one short‐term (7‐days) study suggested a non‐statistically significant “trend” for chlorhexidine mouth rinse to cause a small elevation in systolic blood pressure from 103 mmHg to 106 mHg (Bescos et al., 2020). The clinical significance of this is unknown.

• Depending on the specific agent already selected, a decision must be made regarding their frequency and duration of use.

Intervention

In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed. These products can be delivered as dentifrices.

Available evidence

In the systematic review (Figuero, Roldan, et al., 2019), the adjunctive use of 14 different dentifrice formulations was evaluated for controlling gingival inflammation, with a clear heterogeneity in the number of available studies for each product. The magnitude of effect in gingival indices changes, in formulations with more than one study available, was headed by stannous fluoride with sodium hexametaphosphate (n = 2, S‐WMD = −1.503), followed by triclosan and copolymer (n = 18, S‐WMD = −1.313), and chlorhexidine (n = 2, S‐WMD = −1.278, not statistically significant), although comparing the formulations was not a specific objective of the review. Effects on plaque levels were best with chlorhexidine at high concentrations (n = 3, S‐WMD = −1.512) and triclosan and copolymer (n = 23, S‐WMD = −1.164). In a previously published network meta‐analyses, chlorhexidine and triclosan and copolymer were the most effective agents for plaque reduction, but no clear differences were observed for gingival index control (Escribano et al., 2016; Figuero, Herrera, et al., 2019).

Additional factors have been discussed in the overall evaluation of adjunctive agents.

Intervention

In order to control gingival inflammation during supportive periodontal care, the adjunctive use of some agents has been proposed. These products can be delivered as mouth rinses.

Available evidence

In the systematic review (Figuero, Roldan, et al., 2019), the adjunctive use of 11 different mouth rinse formulations were evaluated for controlling gingival inflammation, with a clear heterogeneity in the number of available studies for each product. The magnitude of effect in gingival indices changes, in formulations with more than one study available, ranged from S‐WMD = −2.248 (essential oils, n = 10), to S‐WMD = −1.499 (cetylpyridinium chloride, n = 5), and to S‐WMD = −1.144 (chlorhexidine at high concentrations, n = 5), although comparing the formulations was not a specific objective of the review. In a previously published network meta‐analyses (a statistical technique which allows the integration of data from direct and indirect comparisons, namely treatments compared among trials through a common comparator treatment), chlorhexidine and essential oil mouth rinses were ranked as the most efficacious agents in terms of changes in plaque and gingival indices (Escribano et al., 2016; Figuero, Herrera, et al., 2019).

Additional factors have been discussed in the overall evaluation of adjunctive agents.

Intervention

Professional mechanical plaque removal (PMPR) administered on a routine basis (i.e. at specific, predetermined intervals) as an integral part of supportive periodontal care has been shown to result in low rates of tooth loss and limited attachment level changes in both the short‐ and long‐term in patients treated for periodontitis (Heasman, McCracken, & Steen, 2002; Trombelli et al., 2015). In most of the studies, PMPR in SPC was often combined with other procedures (e.g. reinforcement of oral hygiene instruction, additional active treatment at sites showing disease recurrence), thus making it difficult to isolate information on the magnitude of the mere effect of PMPR on tooth survival and stability of periodontal parameters (Trombelli et al., 2015).

Available evidence

This issue has not been directly addressed in the systematic reviews prepared for this Workshop; however, ample evidence is available to support this statement. It has been demonstrated that professional mechanical plaque removal (PMPR), performed at defined intervals, together with the other interventions of supportive periodontal care may result in lower rates of tooth loss and attachment level changes. In a systematic review (Trombelli et al., 2015), presented at the 2014 European Workshop, a weighted mean yearly rate of tooth loss of 0.15 and 0.09 for follow‐up of 5 years or 12–14 years, respectively, was reported; the correspondent figures for mean clinical attachment loss lower than 1 mm at follow‐up ranging from 5 to 12 years. Information from this review, and also from other systematic reviews, collectively supports that patients with a history of treated periodontitis can maintain their dentition with limited variations in periodontal parameters when regularly complying with a SPC regimen based on routine PMPR (Sanz et al., 2015).

Risk of bias

The methodological quality was assessed with a specifically designed scale for the evaluation of non‐randomized observational studies, with a quality level ranging from 3 to 7, in a 9‐point scale, with 9 representing the highest quality (lowest risk of bias).

Consistency

Although no meta‐analysis was possible, the primary outcome (tooth loss) was reported in 12 studies, showing no or low incidence. Clinical attachment level (CAL) changes were reported in 10 studies, which consistently showed limited modifications in CAL, frequently as a slight CAL loss.

Clinical relevance and effect size

A weighted mean yearly rate of tooth loss of 0.15 for follow‐up of 5 years, and 0.09 for follow‐up of 12–14 years, can be considered as relevant.

Balance of benefit and harm

PROMs were not reported in the included studies.

Economic considerations

Ethics and legal aspects are not relevant for this intervention; economic aspects have not been frequently addressed. In a study in a private practice in Norway, it was demonstrated that regular maintenance was associated with less tooth loos than not regular maintenance, with follow‐ups of 16–26 years; the yearly cost of maintaining a tooth was estimated in 20.2 euro (Fardal & Grytten, 2014).

Patient preferences

Demonstrated with compliance in long‐term studies.

Applicability

Demonstrated with studies testing large groups from the general population.

Intervention

The systematic review (Trombelli et al., 2015) was retrieving available RCTs on any given alternative intervention to conventional PMPR (the latter including supragingival and/or subgingival removal of plaque, calculus and debris performed with manual and/or powered instruments) in the maintenance of periodontitis patients with a follow‐up of at least 1 year following the first administration of intervention/control treatment.

Available evidence

In the systematic review (Trombelli et al., 2020), only one RCT was identified, assessing Er:YAG laser as an alternative method to conventional PMPR. No statistically significant differences were found (Krohn‐Dale, Boe, Enersen, & Leknes, 2012).

Economic considerations

Cost‐benefit or cost‐effective analyses are missing and may be very relevant when considering this specific treatment option. The same is true for PROMs.

Intervention

The systematic review (Trombelli et al., 2015) was retrieving available RCTs on any given additional intervention to conventional PMPR (the latter including supragingival and/or subgingival removal of plaque, calculus and debris performed with manual and/or powered instruments) in the maintenance of periodontitis patients with a follow‐up of at least 1 year following the first administration of intervention/control treatment.

Available evidence

In the systematic review (Trombelli et al., 2020), two RCTs were identified, one testing sub‐antimicrobial dose (20 mg b.i.d.) of doxycycline (Reinhardt et al., 2007), another evaluating photodynamic therapy (PDT) with a 0.01% methylene blue as photosensitizer and a diode laser (wavelength of 660 nm) (Carvalho et al., 2015). No statistically significant differences were observed in any study, although CAL gain was more relevant with adjunctive PDT (1.54 mm) in comparison with conventional PMPR alone (0.96 mm). The systematic review presented at this Workshop provided information, based on meta‐analysis, of the possible effects of the alternative/adjunctive methods mentioned, with no significant difference for the primary outcome (CAL changes), after 12‐month follow‐up, amounting −0.233 mm (95% CI [−1.065; 0.598; p = .351), favouring the control groups.

Economic considerations

For the adjunctive use of SDD, adverse effects and cost–benefit ratio have to be considered. For the adjunctive use of PDT, a previous systematic review (Xue et al., 2017), which included 11 RCTs, found better results for PDT, but only after 3 months, with 0.13 mm of additional impact in PPD reduction. No increase in adverse events were reported. Cost–benefit or cost‐effective analyses are missing and may be very relevant when considering this specific treatment option.

Intervention

Periodontitis patients benefit from additional risk factor control interventions to improve the maintenance of periodontal stability. Interventions include patient education which be staged and adapted according to individual needs ranging from single brief advice to patient referral for advanced counselling and pharmacotherapy. Smoking and diabetes are two of the main risk factors for periodontitis, and they are currently included in the grading of periodontitis (Papapanou et al., 2018). Controlling these risk factors therefore would be critical for treatment response and for long‐term stability. In addition, other relevant factors, part a healthy life‐style counselling, are considered, including dietary counselling, physical exercise or weight loss. These interventions, together with those for tobacco cessation and diabetes control, are not direct responsibility of oral health professionals, and they may want to refer the patients to other health professionals. However, the direct/indirect role of oral health professionals in these interventions should be emphasized.

Available evidence

In the systematic review (Ramseier et al., 2020), the authors have identified 13 relevant guidelines for interventions for smoking cessation, diabetes control, physical exercise (activity), change of diet, carbohydrate (dietary sugar reduction) and weight loss. In addition, 25 clinical studies were found that assess the impact of (some of) these interventions in gingivitis/periodontitis patients. However, only some of them included patients in supportive periodontal care.

Additional factors have been discussed in the evaluation of risk factor control in patients in active periodontal therapy.

Intervention

Periodontitis patients may benefit from the promotion of diabetes control interventions to improve the maintenance of periodontal stability. The promotion may consist of patient education including brief dietary counselling and possibly patient referral for glycaemic control.

Available evidence

In the systematic review (Ramseier et al., 2020), none of the identified studies was performed in patients in supportive periodontal care. Indirect evidence (see section on active periodontal therapy) suggests that diabetes control interventions ought to be implemented in supportive periodontal care patients.

Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy.

Intervention

Overall evidence from the medical literature suggests that the promotion of physical exercise (activity) interventions may improve both treatment and long‐term management of non‐communicable diseases. In periodontitis patients, the promotion may consist of patient education specifically target to the patients' age and general health.

Available evidence

In the systematic review (Ramseier et al., 2020), none of the identified studies was performed in patients in supportive periodontal care.

Background information and the discussion of additional factors can be found in the section dealing with patients in active periodontal therapy (Billings et al., 2018).