nonsurgical facial rejuvenation: botulinum neuromodulators · 2017-05-30 · personal experience...
TRANSCRIPT
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Nonsurgical Facial Rejuvenation:
Botulinum Neuromodulators
Karol A Gutowski, MD, FACS
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Disclosures
RTI Surgical - Advisor
Suneva Medical - Instructor
Angiotech/Surgical Specialties - Advisory Board
Will discuss off-label uses
Will use brand names for ease of understanding
Will refer to BOTOX Cosmetic as BOTOX
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BoTN-A Product Information
FDA Approved
• BOTOX Cosmetic – OnabotulinumtoxinA
– VISTABEL, VISTABEX
• DYSPORT – AbobotulinumtoxinA
– AZZALURE
• XEOMIN – IncobotulinumtoxinA
– XEOMEEN, BOCOUTURE, NT201
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What FDA Wants You to Know
• Black Box Warning
– Possibility of experiencing potentially life-threatening distant
spread of toxin effect from injection site after local injection
– Not reported in cosmetic uses
• Risk Evaluation and Mitigation Strategy (REMS)
– Medication Guide to help patients understand risks & benefits
• Potency units are specific to each BoTN-A product
– Doses or units cannot be compared or converted
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BoTN-A Mechanism of Action
Block neuromuscular junction transmission by
inhibiting acetyl choline release
• BoTN-A binds to cholinergic nerve terminals
• Internalized into nerve
• Light-chain translocated into nerve cytosol
• Enzymatic cleavage of SNAP-25 (essential for ACh release)
• Impulse transmission re-established by formation of new nerve
endings
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BoTN-A Mechanism of Action
• Block cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerve endings.
• Neurotoxin binding to cholinergic nerve terminals, internalization of the neurotoxin into the nerve terminal, translocation of the light-chain part of the molecule into the cytosol of the nerve terminal, and enzymatic cleavage of SNAP25, a presynaptic target protein essential for the release of acetylcholine. Impulse transmission is re-established by the formation of new nerve endings.
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Product Comparison
(Inactive ingredients)
HAS = Human Serum Albumin
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Product Composition
(Inactive ingredients)
HAS = Human Serum Albumin
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Product Composition
(Inactive ingredients)
HAS = Human Serum Albumin
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Product Composition
(Inactive ingredients)
HAS = Human Serum Albumin
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BoTN-A Protein Comparison
BOTOX DYSPORT XEOMIN
No Accessory Proteins
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Pivotal Study Doses
BoTN-A Dilution Glabella Duration
BOTOX 4u/0.1 cc 4 u at 5 sites 3-4 months
DYSPORT 10u/0.08 cc 10 u at 5 sites 3-4 months
XEOMIN 4u/0.1 cc 4 u at 5 sites 3 months
Dilution and dosage may vary as determined by clinician
Adjusting dose to target muscle mass may improve outcome and duration
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Pivotal Study Doses
BoTN-A Dilution Glabella Duration
BOTOX 4u/0.1 cc 4 u at 5 sites 3-4 months
DYSPORT 10u/0.08 cc 10 u at 5 sites 3-4 months
XEOMIN 4u/0.1 cc 4 u at 5 sites 3 months
Dilution and dosage may vary as determined by clinician
Adjusting dose to target muscle mass may improve outcome and duration
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BOTOX Pivotal Studies
50% of patients maintain improvement at 3 months
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DYSPORT Pivotal Studies
40% - 50% of patients maintain 1-Grade improvement at 3 months
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Dysport Dose Response
30U & 45U better than 15U
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Dysport Dose Response
Patient satisfaction similar at all doses
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Dysport Dose Response
Older patients less likely to respond
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XEOMIN Pivotal Studies
15% - 25% of patients maintain 2-Grade improvement at 3 months
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Xeomin Phase 3 Post Hoc Analysis
• Issue of 1 vs 2 point clinical
response
• 20u divided in 5 glabella sites
• Response no worse (or better)
than Botox
> 1 point improvement
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Xeomin vs Botox
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BOTOX vs DYSPORT Duration
Lowe, J Am Acad Dermatol 2006
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BOTOX vs XEOMIN Dose
Meta-analysis established 1:1 dose effectiveness but not duration
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Fields of Effect
• Dysport greater
anhidrotic effect
than Xeomin
• Similar muscular
effects by EMG2.5:1.0 Dysport to Xeomin
Xeomin Dysport
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Personal Experience
• Fastest time to onset DYSPORT (1-3 days)
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Personal Experience
• Fastest time to onset DYSPORT (1-3 days)
• Duration Equal
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Personal Experience
• Fastest time to onset DYSPORT (1-3 days)
• Duration Equal
• Cost* BOTOX > DYSPORT > XEOMIN
* Depends on dose & rebates
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Personal Experience
• Fastest time to onset DYSPORT (1-3 days)
• Duration Equal
• Cost* BOTOX > DYSPORT > XEOMIN
• Pain Same (technique?)
• Spread Same (dilution & technique?)
* Depends on dose & rebates
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Personal Experience
• Fastest time to onset DYSPORT (1-3 days)
• Duration Equal
• Cost* BOTOX > DYSPORT > XEOMIN
• Pain Same (technique?)
• Spread Same (dilution & technique?)
• Dose 1BOTOX = 1XEOMIN = 3DYSPORT
* Depends on dose & rebates
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Personal Experience
• Accessory proteins Do they matter?
• Interchangeable Maybe (more similar than different)
• Split face Not much difference
• Patient cross-over Not much difference
• BOTOX non-responders It’s the same molecule but worth a try?
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Applications
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Observe Patient During Conversation
• Watch for expressions & muscle movements
during a normal conversation
• More appropriate initially than treating
exaggerated or extreme movements
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Patient Education
• Explain what it can & what it can’t improve
• Introduce the “4 R’s”
– Relax, Resurface, Refill, then Relift
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Product Dilutions
Assume vial with 100 units of BOTOX
• 1.0cc = 10u/0.1 cc
• 2.0 cc = 5u/0.1 cc
• 2.5 cc = 4u/0.1 cc
• 4.0 cc = 2.5u/0.1cc
Low injection volume limits diffusion (Glabella)
More product waste
High injection volume increases diffusion (Forehead)
Less product waste
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Injection
Assume vial with 100 units of BOTOX
• 1.0cc = 10u/0.1 cc
• 2.0 cc = 5u/0.1 cc
• 2.5 cc = 4u/0.1 cc
• 4.0 cc = 2.5u/0.1cc
0.3 cc insulin syringe with fixed 31G needle
Needle dulls after a few injections
1.0 cc syringe with removable 32G needle
(Less discomfort than 30G needle)
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Document the Treatment
Jenny Smith 10/2/14None
Loved it!
None
27
XX
B32
C 32 1578
Voluma 13-578
V
F= 2u x6 = 12u
Malar = 0.5cc per side
May need more in 2 weeks
22
2 22
2
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BoTN-A Non-responders
• True non-responders are rare
• May have antibodies to BoTN-A
– Presence of antibody ≠ no response
– Absence of antibody ≠ response
• Antibodies may disappear over time
• May respond to BoTN-B (Myobloc)
– Acts on synaptobrevin (not SNAP-25)
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Zinc Supplementation to Increase Duration
• Double-blinded, placebo-controlled cross-over study
• Inclusion: “Hard to Treat” patients
• BOTOX, DYSPORT, XEOMIN
• BoTN-A is zinc dependent
• Phytates block zinc absorption
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Zinc Supplementation to Increase Duration
• 92% of patients reported 30% increase in duration
• Older patients
– Greater improvement
– No increase in duration
• Zytase $40 per treatment
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Can I Really Store BoTN-A for 4 Weeks?
• Literature review & 2 round Delphi process
• Can be refrigerated or refrozen for 4 weeks
• Can use on multiple patients (proper handling)
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Does Injection Depth Matter?
Selective eyebrow depressors cannot be targeted
due to BoTN diffusion radius
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Clinical Examples
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PRS Supplement 2015
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Individual Patient Assessment for Natural Result
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BoTN-A & the Four R’s
• Relax the muscle: BoTN-A
• Refill the face (volume): Fillers
• Resurface the skin: Lasers
– Fractional CO2
• Relift the tissue: Energy-based
– Ultherapy
– Neck laser-assisted liposuction
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Eyelid Ptosis Reversal
• Alpha-adrenergic agonist ophthalmic eye drops
– Apraclonidine 0.5% (Iopidine)
– Naphazoline (Naphcon)
– Phenylephrine 2.5% (Myfrin)
• Stimulate Mueller’s muscle elevate ptotic eyelid
– Typical 2 mm of lid elevation
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Nonsurgical Facial Rejuvenation:
Botulinum Neuromodulators