Treating the Infected Periodontal Foundation

Treating the Infected
Periodontal Foundation
OraPharma, Inc. 2008
Topics included in this discussion
•
Prevalence and pathogenesis of periodontal disease
– Red complex bacteria
– Properties of biofilms
– Links to systemic complications
– Limitations of mechanical treatment
•
Treatment with ARESTIN® (minocycline hydrochloride)
Microspheres, 1 mg
– Microsphere technology
– Eradication of red complex bacteria
– Proven clinical outcomes
– Smokers and difficult-to-treat patient groups
– Safety and ease of use
Periodontal disease is a common, chronic,
and persistent infection1-6
•
Periodontal disease is:
– A persistent infection that can spread rapidly
throughout the periodontium1,2
– The most common chronic bacterial infection
in adults1,3
– A problem that affects more than 35.7
million Americans4
– The #1 cause of adult tooth loss in the US5
•
Three out of 4 American adults develop a
periodontal infection6
References: 1. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000
2002;28:12-55. 2. Page RC. Periodontal diseases: a new paradigm. J Dent Educ 1998;62:812-821.
3. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and
treatment. Clin Microbiol Rev 2001;14:727-752. 4. Albandar JM, Brunelle JA, Kingman A. Destructive
periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol
1999;70:13-29. 5. Williams RC. Periodontal disease. N Engl J Med 1990;322:373-382. 6. American Dental
Association. For the dental patient. Women and periodontal disease. J Am Dent Assoc 2002;133:671.
Red complex bacteria are found at the
infection site
•
Specific bacteria are implicated in periodontal disease and are
commonly found at the site of infection1,2
•
There is a direct association between red complex bacteria and 2 of
the most meaningful parameters in periodontal disease diagnosis1:
– Pocket depth
– Bleeding on probing
References: 1. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in
subgingival plaque. J Clin Periodontol 1998;25:134-144. 2. Socransky SS, Haffajee AD. Dental biofilms:
difficult therapeutic targets. Periodontol 2000 2002;28:12-55.
Periodontal bacteria form dense biofilms
•
The bacteria associated with
periodontal disease reside
within biofilms above and
below the gingival margin1-3
•
Biofilms are dense mixtures
of organisms resistant to
natural antibodies and proteins
that the body uses to fight
infection1
Slide content adapted with permission from Dr. Richard H. Nagelberg.
References: 1. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol
2000 2002;28:12-55. 2. Scannapieco FA. Periodontal inflammation: from gingivitis to systemic disease?
Compend Contin Educ Dent 2004;25(suppl 1):16-25. 3. Page RC. Periodontal diseases: a new
paradigm. J Dent Educ 1998;62:812-821.
Collectively, the structure and properties of
biofilms make it difficult to remove them with
SRP alone1,2
•
Biofilms possess a self-protective matrix shield1
•
Each contains a microenvironment of bacteria1,2
– Bacteria exist in large numbers
– Bacteria rapidly multiply, spread, and recolonize
•
Biofilms cross-feed and cross-communicate1,2
•
Loosely attached and unattached bacteria found at the biofilm
surface have direct contact with the epithelium of the gingival tissue2
Slide content adapted with permission from Dr. Richard H. Nagelberg.
References: 1. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000
2002;28:12-55. 2. Page RC. Periodontal diseases: a new paradigm. J Dent Educ 1998;62:812-821.
Biofilms shelter millions of bacteria1
•
Approximately 10 million to 1 billion bacteria have been observed in
the biofilm-infected periodontal pocket1
•
The depth of biofilm-infected pockets ranges from 4 mm to 12 mm1
Slide content adapted with permission from Dr. Richard H. Nagelberg.
Reference: 1. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection:
diagnosis and treatment. Clin Microbiol Rev 2001;14:727-752.
Biofilms can induce bacteremia1
•
Biofilms release a variety of biologically
active inflammatory products, including:
– Bacterial endotoxins
– Protein toxins
– Peptides
– Organic fatty acids
•
These destructive molecules cause
gingival inflammation and can enter
the bloodstream, resulting in bacteremia
Slide content adapted with permission from Dr. Richard H. Nagelberg.
Reference: 1. Scannapieco FA. Periodontal inflammation: from gingivitis to systemic disease? Compend
Contin Educ Dent 2004;25(suppl 1):16-25.
Bacteremia generates an inflammatory
response1,2
•
The body responds to bacteremia with
inflammation and tissue destruction1
•
The body releases cytokines, small
proteins responsible for gingival
inflammation1
•
Cytokines induce and enhance the
production of a destructive family of
enzymes, also known as MMPs1,2
•
MMPs break down gingival tissue,
leading to the formation of periodontal
disease2
Slide content adapted with permission from Dr. Richard H. Nagelberg.
References: 1. Scannapieco FA. Periodontal inflammation: from gingivitis to systemic disease? Compend
Contin Educ Dent 2004;25(suppl 1):16-25. 2. Page RC. Periodontal diseases: a new paradigm. J Dent Educ
1998;62:812-821.
C-reactive protein (CRP) levels are elevated
in patients with periodontal infection
•
Statistically significant increases in CRP
have been observed in patients with
periodontal infection vs healthy patients1
•
CRP has been linked to a number of
important systemic events2,3
Slide content adapted with permission
from Dr. Richard H. Nagelberg.
References: 1. Noack B, Genco RJ et al. Periodontal infections contribute to elevated systemic C-reactive
protein level. J Periodontol 2001;72:1221-1227. 2. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR.
Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first
cardiovascular events. N Engl J Med 2002:347:1557-1565. 3. American Heart Association. Inflammation,
heart disease, and stroke: the role of C-reactive protein. Available at:
http://www.americanheart.org/presenter.jhtml?identifier=4648. Accessed June 18, 2006.
The American Academy of
Periodontology (AAP) links periodontal
disease to other serious health risks*
According to the AAP1:
•
Periodontal bacteria can enter the blood stream, travel to major organs,
and begin new infections
•
Current research suggests that periodontal bacteremia may lead to:
– Heart disease, stroke, and/or diabetes
– Increased risk of delivering a preterm, low birth-weight baby
– Increased health risk for people with diabetes, respiratory disease,
or osteoporosis
*A causal relationship has not been fully established.
Reference: 1. American Academy of Periodontology. Mouth body connection. Available at:
http://www.perio.org/consumer/mbc.top2.htm. Accessed June 17, 2006.
Routine, effective treatment for
periodontal infection is needed
•
Despite the prevalence of periodontal infection and the persistent
nature of bacteria and biofilms, more than 70% of dental practices
do not perform regular full-mouth probing and charting1
•
Although 3 out of 4 American adults are affected by
periodontal disease2:
– Prophylaxis procedures outnumber SRP procedures by a
ratio of 20:13,4
– Less than 1/2 of periodontal pockets are treated with
adjunctive therapy5*
*According to a utilization tracking survey evaluating 14,945 patient records from 647 offices.
The average number of pockets per patient was 9.
References: 1. Levin RL. Periodontal profitability. Available at: http://www.dentaleconomics.com. Accessed
December 26, 2005. 2. American Dental Association. For the dental patient. Women and periodontal
disease. J Am Dent Assoc 2002;133:671. 3. Blair C. The economic impact of the underdiagnosis of
periodontal disease in general practice. Triage 2005;1:21-25. 4. American Dental Association, Survey
Center. 1999 Survey of Dental Services Rendered. Chicago, IL: American Dental Association; 1999. 5. Data
on file. OraPharma, Inc., Warminster, PA; 2004.
Left untreated, serious consequences
can occur
Without proper diagnosis and treatment, periodontal disease can lead to…
The spread of infection1
Loss of teeth2
Surgery2
References: 1. Page RC. Periodontal diseases: a new paradigm. J Dent Educ 1998;62:812-821.
2. Williams RC. Periodontal disease. N Engl J Med 1990;322:373-382.
Scaling and root planing (SRP) has
mechanical limitations
•
Even after SRP, the bacteria in biofilms
can remain, multiply, and return to baseline
levels within days1
•
SRP instrumentation is limited in areas of
restricted access2,3
•
In a clinical study, 58% of sites had
residual calculus after SRP4
References: 1. Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000
2002;28:12-55. 2. Cobb CM. Non-surgical pocket therapy: mechanical. Ann Periodontol 1996;1:443-490.
3. Cobb CM. Implementing New Strategies for Treating Periodontal Disease: A Systematic Approach.
Symposium. October 2, 2002. Chicago, IL. 4. Sherman PR, Hutchens LH Jr., Jeson LG, Moriarty JM,
Greco GW, McFall WT Jr. The effectiveness of subgingival scaling and root planing. I. Clinical detection of
residual calculus. J Peridontol 1990;61:3-8.
Instrumentation
does not always
reach the
furcation region.
Deep pockets can
restrict access and
create a reservoir
for bacteria.
Adding an LAA to SRP can benefit patients
•
Adding a locally administered antibiotic (LAA) to SRP is proven to
significantly improve periodontal treatment1
•
The American Academy of Periodontology (AAP) supports the use
of LAAs as an adjunct to SRP2
•
The LAA ARESTIN® (minocycline hydrochloride) Microspheres,
1 mg can help eliminate the bacteria that SRP can leave behind
including3,4:
– P gingivalis
– T denticola
– T forsynthensis
References: 1. Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local
administration of minocycline microspheres: a controlled trial. J Periodontol 2001;72:1535-1544. 2.
American Academy of Periodontology Research, Science, and Therapy Committee. Guidelines for
periodontal therapy. J Periodontol 2001;72:1624-1628. 3. ARESTIN® (minocycline hydrochloride) 1 mg
Microspheres [Prescribing Information]. Warminster, PA: OraPharma, Inc., 2005. 4. Data on file.
OraPharma, Inc., Warminster, PA; 2004.
ARESTIN® Microspheres technology provides a
sustained release of minocycline in the
periodontal pocket1
•
•
•
ARESTIN® Microspheres
deliver minocycline directly to
the periodontal pocket and help
maintain therapeutic drug
concentrations for up to 21
days, managing the infection
long after treatment with SRP1
ARESTIN® Microspheres are
bioadhesive and completely
bioresorbed2
ARESTIN® Microspheres kill
the bacteria SRP leaves
behind, including P gingivalis,
T denticola, and
T forsynthensis
References: 1. Data on file. OraPharma, Inc., Warminster, PA; 2004. 2. ARESTIN® (minocycline
hydrochloride) 1 mg Microspheres [Prescribing Information]. Warminster, PA: OraPharma, Inc., 2005.
Baseline
2 Days
10 Days
Minocycline effectively treats the common
periodontal pathogens1
References: 1. ARESTIN® (minocycline hydrochloride) 1 mg Microspheres [Prescribing Information].
Warminster, PA: OraPharma, Inc., 2005. 2. Data on file. OraPharma, Inc., Warminster, PA; 2004.
3. O’Connor BC, Newman HN, Wilson M. Susceptibility and resistance of plaque bacteria to minocycline.
J Periodontol 1990;61:228-233.
ARESTIN® treats the bacterial cause of
periodontal infection more effectively than
SRP alone1*
In a recent microbiological study
of patients with moderate-tosevere periodontitis,
ARESTIN® + SRP:
•
Significantly reduced the
quantity of red complex
bacteria vs SRP alone
(P=0.002)
*Phase IV, single-blind, randomized, parallel-group study of 127 patients with
moderate-to-severe periodontitis and at least 5 teeth with 5 mm pocket depths.
Reference: 1. Goodson, JM. Antimicrobial Efficacy of Arestin in Periodontitis Therapy. Presented at the
35th Annual Meeting of the American Association for Dental Research; March 8-11, 2006; Orlando, FL.
ARESTIN® treats the bacterial cause of
periodontal infection more effectively than
SRP alone1*
In a recent microbiological study
of patients with moderate-tosevere periodontitis,
ARESTIN® + SRP:
•
•
Significantly reduced
proportions of red complex
bacteria vs SRP alone
(P=0.0005)
Significantly reduced pocket
depths and bleeding on probing,
and increased clinical
attachment levels2
*Phase IV, single-blind, randomized, parallel-group study of 127 patients with moderate-tosevere periodontitis and at least 5 teeth with 5 mm pocket depths.
Reference: 1. Goodson, JM. Antimicrobial Efficacy of Arestin in Periodontitis Therapy. Presented at the
35th Annual Meeting of the American Association for Dental Research; March 8-11, 2006; Orlando, FL.
2. Bland PS. Clinical efficacy and safety with ARESTIN® in patients with periodontitis. Presented at the
35th Annual Meeting of the American Association for Dental Research; March 8-11, 2006; Orlando, FL.
ARESTIN® + SRP is significantly more effective
than SRP alone in reducing pocket depth1
ARESTIN® + SRP demonstrated a greater therapeutic effect than SRP
alone throughout 9 months (P<0.001)1
*P<0.01 ARESTIN® vs SRP alone
†P<0.001 ARESTIN® vs SRP alone
‡P<0.001 ARESTIN® vs SRP + placebo
Reference: 1. Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local
administration of minocycline microspheres: a controlled trial. J Periodontol 2001;72:1535-1544.
ARESTIN® + SRP is significantly more effective
than SRP alone in reducing pocket depth1
More than 60% of pockets that responded to ARESTIN® + SRP had a
reduction of >2 mm1*
• In 65% of patients, ARESTIN®
+ SRP reduced pocket depth
from >6 mm to <5 mm1
•
Compared to SRP alone,
ARESTIN® + SRP is nearly
3 times more likely to reduce
mean probing depth from >6
mm to <5 mm2
*In clinical studies, 37% of pockets treated with SRP alone did not respond to therapy vs
29% of pockets treated with ARESTIN® + SRP.1
References: 1. Data on file. OraPharma, Inc., Warminster, PA; 2004. 2. Williams RC, Paquette DW,
Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a
controlled trial. J Periodontol 2001;72:1535-1544.
Smoking is a major risk factor for
periodontal infection1,2
•
Smoking may be responsible for more than 1/2 of adult periodontal
cases in the US3
•
Clinical studies show that smokers exhibit increased1,2:
– Pocket depth
– Alveolar bone loss
– Gingival recession
– Tooth loss
Radiograph showing bone loss in
– Clinical attachment loss
smoker with periodontal disease.
– Number of furcations
References: 1. Kerdvongbundit V, Wikesjö UME. Prevalence and severity of periodontal disease at
mandibular molar teeth in smokers with regular oral hygiene habits. J Periodontol 2002;73:735-740.
2. American Academy of Periodontology Research, Science and Therapy Committee. Tobacco use and the
periodontal patient. J Periodontol 1999;70:1419-1427. 3. Tomar SL, Asma S. Smoking-attributable
periodontitis in the United States: findings from NHANES III. J Periodontol 2000;71:743-751.
ARESTIN® + SRP is more effective than SRP alone
in reducing pocket depth in smokers with
periodontal disease1
Statistically significant pocket depth reduction vs SRP alone1*
*Subgroup analysis (n=271)1 of the single-blind, Phase III trial comparing ARESTIN® + SRP to SRP alone and
SRP + placebo (n=748).2 SRP was performed for all groups at baseline. ARESTIN® or vehicle was
administered to periodontal pockets >5 mm in the adjunctive therapy groups at baseline, 3 months,
and 6 months. Efficacy was evaluated over 9 months.
References: 1. Paquette D, Oringer R, Lessem J, et al. Locally delivered minocycline microspheres for the
treatment of periodontitis in smokers. J Clin Periodontol 2003;30:787-794. 2. Williams RC, Paquette DW,
Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a
controlled trial. J Periodontol 2001;72:1535-1544.
ARESTIN® + SRP is more likely than SRP alone to
reduce pockets to maintenance levels in smokers1
•
According to the AAP, smokers can be up to 6x more likely to
exhibit periodontal destruction vs nonsmokers2
•
Compared to SRP alone, ARESTIN® + SRP is nearly 4x more likely
to reduce periodontal pockets to <5 mm in smokers1*
*Multivariate analysis of the univariate, multicenter Phase III trials of ARESTIN® that compared
the efficacy and safety of ARESTIN® + SRP to SRP + placebo and SRP alone. Odds ratios were
adjusted to allow for the simultaneous effect of influential variables, such as treatment center,
smoking status, age, and baseline pocket depths.
References: 1. Data on file. OraPharma, Inc., Warminster, PA; 2004. 2. American Academy of
Periodontology Research, Science and Therapy Committee. Tobacco use and the periodontal patient.
J Periodontol 1999;70:1419-1427.
ARESTIN® + SRP has a greater therapeutic effect
than SRP alone* in other difficult-to-treat
patient groups1-3
Based on pocket depth reduction scores at 9 months†
Greater therapeutic
effect*‡
*Adapted from Williams RC, Paquette DW, Offenbacher S, et al.4
†748 patients with moderate or advanced periodontitis with bleeding on probing. SRP was performed at baseline. Clinical
assessments were conducted at baseline and 1, 3, 6, and 9 months. ARESTIN® or vehicle was administered to all sites with
pocket depths >5 mm.
‡Change in pocket depth from baseline to 9 months was recorded for ARESTIN® + SRP and SRP alone.
Therapeutic effect was derived by calculating the percent difference between the 9-month scores.
References: 1. Williams RC. Periodontal disease. N Engl J Med 1990;322:373-382. 2. Cobb CM. Non-surgical
pocket therapy: mechanical. Ann Periodontol 1996;1:443-490. 3. Fleischer HC, Mellonig JT, Brayer WK, Gray
JL, Barnett JD. Scaling and root planing efficacy in multirooted teeth. J Periodontol 1989;60(7):402-409.
4. Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local administration of
minocycline microspheres: a controlled trial. J Periodontol 2001;72:1535-1544.
ARESTIN® is easy to administer
The administration of ARESTIN® does not require local anesthesia.
Sterilize the handle tip between patients. ARESTIN® does not have to
be removed, as it is bioresorbable. ARESTIN® does not require an
adhesive or dressing.
Insert the ARESTIN®
cartridge into the handle
while exerting slight
pressure.
Twist until you feel and
hear the cartridge
“lock” into place.
Should you need to manipulate the
cartridge tip to reach difficult-to-access
areas, gently bend the tip, leaving the
blue cap on. Bending the tip after
removal of the blue cap may cause
the internal plunger to rupture the
cartridge wall.
ARESTIN® is easy to administer
Place the cartridge tip
into the periodontal
pocket, parallel to the
long axis of the tooth.
Be sure not to force the
tip into the base of the
pocket.
Gently press the thumb ring
to express the ARESTIN®
powder while withdrawing
the cartridge tip away from
the base of the pocket. If
you feel any resistance
during delivery, withdraw the
device further.
Once delivery is complete,
retract the thumb ring and
remove the ARESTIN®
cartridge with your free hand.
Appropriately discard the
cartridge and sterilize the
handle prior to reuse.
ARESTIN® is safe and well tolerated in
clinical trials1
Reference: 1. ARESTIN® (minocycline hydrochloride) 1 mg Microspheres [Prescribing Information].
Warminster, PA: OraPharma, Inc., 2005.
Summary
•
Three out of 4 American adults develop periodontal disease,1 yet
this persistent infection often goes untreated2-4
•
The AAP reports that periodontal bacteria can enter the blood
stream, travel to major organs, begin new infections, and potentially
lead to additional health problems5,6*
•
SRP instrumentation has mechanical limitations and can leave
bacteria behind in the periodontium7,8
*A causal relationship has not been fully established.
References: 1. American Dental Association. For the dental patient. Women and periodontal disease.
J Am Dent Assoc 2002;133:671. 2. Blair C. The economic impact of the underdiagnosis of periodontal
disease in general practice. Triage 2005;1:21-25. 3. American Dental Association, Survey Center. 1999
Survey of Dental Services Rendered. Chicago, IL: American Dental Association; 1999. 4. Data on file.
OraPharma, Inc, Warminster, PA; 2004. 5. American Academy of Periodontology. Mouth body connection.
Available at: http://www.perio.org/consumer/mbc.top2.htm. Accessed June 17, 2006. 6. American Academy
of Periodontology Research, Science, and Therapy Committee. Diabetes and periodontal diseases.
J Periodontol 1999;70: 935-949. 7. Cobb CM. Non-surgical pocket therapy: mechanical. Ann Periodontol
1996;1:443-490. 8. Cobb CM. Implementing New Strategies for Treating Periodontal Disease: A Systematic
Approach. Symposium. October 2, 2002. Chicago, IL.
Summary, continued
•
ARESTIN® is a locally administered antibiotic that can help eliminate the
bacteria that SRP leaves behind1
•
ARESTIN® maintains therapeutic drug concentrations in the periodontal
pocket for up to 21 days,2 managing the infection long after treatment with
SRP
•
ARESTIN® + SRP has been shown to significantly reduce quantity and
proportions of red complex bacteria vs SRP alone3
•
ARESTIN® is significantly more effective than SRP alone in reducing
periodontal pocket depth, even in smokers and difficult-to-treat patients4
References: 1. ARESTIN® (minocycline hydrochloride) 1 mg Microspheres [Prescribing Information].
Warminster, PA: OraPharma, Inc., 2005. 2. Data on file. OraPharma, Inc., Warminster, PA; 2004. 3. Goodson,
JM. Antimicrobial Efficacy of Arestin in Periodontitis Therapy. Presented at the 35th Annual Meeting of the
American Association for Dental Research; March 8-11, 2006; Orlando, FL. 4. Williams RC, Paquette DW,
Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a
controlled trial. J Periodontol 2001;72:1535-1544.
ARESTIN® Safety Information
ARESTIN® is indicated as an adjunct to scaling and root planing (SRP)
procedures for reduction of pocket depth in patients with adult periodontitis.
ARESTIN® may be used as part of a periodontal maintenance program which
includes good oral hygiene, and scaling and root planing.
ARESTIN® contains minocycline, a tetracycline derivative, and therefore
should not be used in children and in pregnant or nursing women. The use
of drugs of the tetracycline class during tooth development may cause
permanent discoloration of the teeth.
The most common treatment-emergent adverse events were headache
(9.0%), infection (7.6%), flu syndrome (5.0%), and pain (4.3%). These
occurred at a similar rate to SRP and SRP + placebo.
Please see accompanying full Prescribing Information.
©2006 OraPharma, Inc.
A-456-06 12/06
ARESTIN® is a registered trademark of OraPharma, Inc.