percutaneous tibial nerve stimulation - iuga...
TRANSCRIPT
Percutaneous tibial nerve stimulation
Prof. Jan-Paul Roovers, uro-gynaecologist, Head dpt of gynaecology, AMC Amsterdam
Medical director Pelvic floor center “Bergman clinics”
Pre
senta
tionA
MC
.pp
tx
1
OAB – Urgency - The Driver for Multiple Symptoms
Urgency
Increased
Frequency
and Reduced
Intervoid
Interval
Nocturia Incontinence
Quality of
Life
Perception
of Bladder
Condition
“Bother”
Reduced Volume
Voided per Micturition
Modified from Chapple CR , Artibani W, Cardozo LD, Castr-Diaz D, Craggs M, Haab F et al. BJU Int. 2005; 95: 335–40
Pre
senta
tionA
MC
.pp
tx
2
Bladder Filling Sensations
Different for Detrusor Overactivity and Urodynamic
Stress Incontinence
Urodynamic
diagnosis
Abdominal
sensation
Perineal
sensation
Abdominal &
Perineal
sensation
Total
Detrusor
overactivity 3 13 1 17
Urodynamic
stress
incontinence
12 2 4 18
Mixed
urodynamic
diagnosis
1 6 3 10
Normal
urodynamics 4 7 0 11
Reduced bladder
sensation 1 1 0 2
Basra R et al. Int Urogynecol J 2006; 17(suppl 2): S134 Abst 130 Slide Provided by Mr V Khullar
Pre
senta
tionA
MC
.pp
tx
3
Innervation of the Human Bladder
Cortex: permission & attention
Midbrain: safety
Brainstem: relay center „on /off‟
Th10-L2: sympathetic nerve: storage
S2-3: parasympathetic system: voiding
S2-3: pudendal nerve: control
Pre
senta
tionA
MC
.pp
tx
4
Innervation of the Bladder
4
Pre
senta
tionA
MC
.pp
tx
5
The Emerging Picture is Complex
Pain Pain C fibres
Gillespie JI, van Koeveringe GA, de Wachter SG, de Vente J. BJU Int. 2009; 103: 1324-1333
Static - mechanical
Chemical
Mechanical
Motor/sensory
medulla
cord
CNS
HT fibres LT fibres
Silent fibres
Stretch receptors Aδ/C Stretch receptors
Urothelial modulation
Myofibroblasts
Motor/sensory
Detrusor contraction
M 3
cortex
Pre
senta
tionA
MC
.pp
tx
6
Working mechanism of PTNS
Pre
senta
tionA
MC
.pp
tx
7
OAB symptoms are the result of disbalance between
inhibitory and excitatory control systems
1.Sensory input through pudendal nerve inhibits detrusor
activity and enhances external sphincter tone. This facilitates
storage of urine.
2.Bladder normally responds to neural stimulation with rapid
contraction and slow, longer lasting relaxation. With recurrent
repetitive stimuli, the bladder response is down regulated.
Hypothesis working mechanism PTNS
7
Finazzi-Agrò, E., et al. (2009). Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the
long latency somatosensory evoked potentials. Neurourol Urodyn, 28(4):320-24.
Pre
senta
tionA
MC
.pp
tx
8
1.
2.
3. Stimulation of afferent sacral nerves in lower extremities
increases the inhibitory stimuli to the efferent pelvic nerve
and reduces detrusor contractility.
4. Affects the neuro-axis and restores balance between
inhibitory and excitatory regulation at various locations.
8
Finazzi-Agrò, E., et al. (2009). Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the
long latency somatosensory evoked potentials. Neurourol Urodyn, 28(4):320-24.
Hypothesis working mechanism PTNS
Pre
senta
tionA
MC
.pp
tx
9
• It is feasible to effectively influence behaviour of the lower
urinary tract via the Posterior Tibial Nerve
• Discontinuous stimulation can work for some time after the
stimulation has stopped
Concept of PTNS
9
Finazzi-Agrò, E., et al. (2009). Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the
long latency somatosensory evoked potentials. Neurourol Urodyn, 28(4):320-24.
Pre
senta
tionA
MC
.pp
tx
10
Sites of Neuromodulation for LUTS
Mixed
pudendal
nerves
•Anal/Vaginal [Fall et al 1978]
•Dorsal Clitoral/Penile Nerve [Nakamura & Sakurai 1984,
Fjorback et al 2007]
Pudendal
Afferent
nerves
sacral
nerves
•Sacral Nerve Implants
[Schmidt 1988]
Pre
senta
tionA
MC
.pp
tx
11
• 1983 – McGuire - treated urge, frequency, and
incontinence with tibial nerve electrical stimulation
• 1999 – Stoller – modified technique using near nerve
needle stimulation
• Tibial nerve stimulation is more acceptable than
genital/anal stimulation
Why the Tibial Nerve?
11
Pre
senta
tionA
MC
.pp
tx
12
Tibial Nerve Pathway
• Innervates muscles
including big toe flexor
• A toe extension may not
be present in all cases
12
Pre
senta
tionA
MC
.pp
tx
13
Tibial Nerve Pathway • Mixed peripheral nerve
• Sensory and motor fibers
• Spinal segments from
L4 to S3
• Contains sensory fibers –
cutaneous afferents
innervating the sole and heel
• Contains motor fibers – flex
& fan toes
• Accessible at ankle &
superficial enough to reach
13
Pre
senta
tionA
MC
.pp
tx
14
Urgent® PC Neuromodulation System
14
Pre
senta
tionA
MC
.pp
tx
15
PTNS: Procedure
• “frog” position (optional)
• puncture 5 cm upwards of the medial malleolus
• attach reference electrode
• connect to stimulator
• adjust stimulator current
Pre
senta
tionA
MC
.pp
tx
16
• Sensory response
• radiating sensation in
the sole of the foot
• Motor response
• toe flexion and/or
fanning
PTNS: Procedure
Pre
senta
tionA
MC
.pp
tx
17
PTNS: Protocol
• 12 (bi)weekly sessions of 30 min.
• Adjust stimulation intensity during session
• Out-patient setting
• Performed by doctor or nurse practitioner
• Success expected after 6-8 sessions
• Successful cases: continue as the patient requires (tapering protocol) once every 2 - 4 weeks
Pre
senta
tionA
MC
.pp
tx
18
Indications
18
• OAB syndrome (OAB wet and OAB dry)
• Pelvic Pain
• Voiding Dysfunction
• Fecal incontinence
Pre
senta
tionA
MC
.pp
tx
19
• Patients who are pregnant or planning to become pregnant
while using this product
• Patients with pacemakers or implantable defibrillators
• Patients prone to excessive bleeding
• Patients with nerve damage that could impact either
percutaneous tibial nerve or pelvic floor function
Urgent PC Contraindications
19
Pre
senta
tionA
MC
.pp
tx
20
Clinical data on PTNS
• Meta-Analyses
• OrBIT - RCT compared to drug
• SUmiT - RCT compared to placebo
• Long-Term Data
• OrBIT 12 month – Results sustained for 12 months
• STEP – up to 3 years
• “Real Life” Clinical Studies
20
Pre
senta
tionA
MC
.pp
tx
21
• Reduce leak episodes by > 50%
• Reduce frequency to < 8 voids/24 hr (normal)
• Patient requests continuation of therapy
Clinical Success Measurements
21
Pre
senta
tionA
MC
.pp
tx
22
60 – 80% Response
22
Pre
senta
tionA
MC
.pp
tx
23
• Multicenter, RCT
• 12 week phase
• 12 month responder follow-up
• 1:1 randomization (n=100)
• Physician and patient impression of improvement
• Voiding diaries, QoL measures
OrBIT – PTNS versus tolterodine
23
Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.
(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the
Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.
Pre
senta
tionA
MC
.pp
tx
24
OrBIT Results at 12 Weeks
24
Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.
(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the
Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.
Pre
senta
tionA
MC
.pp
tx
25
OrBIT Results at 12 Weeks
25
*p-value: 0.053
Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.
(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the
Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.
Pre
senta
tionA
MC
.pp
tx
26
• Constipation reported less often in PTNS arm
compared to drug arm (p=0.04)
• Dry mouth reported less often in PTNS arm
compared to drug arm (p < 0.001)
• PTNS group reported pain, discomfort or redness
at ankle (assessed for PTNS group only)
OrBIT – Adverse events
26
Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.
(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the
Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.
Pre
senta
tionA
MC
.pp
tx
27
OrBIT 12 Week Conclusion
Urgent® PC and slow release tolterodine provide
similar (significant) objective and subjective
improvement.
27
Peters, K., MacDiarmid, S., Wooldridge, L., Leong, F., Shobeiri, S., Rovner, E., Siegel, S., Tate, S., Jarnagin, B., Rosenblatt, P., & Feagins, B.
(2009). Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the
Overactive Bladder Innovative Therapy Trial. J Urol, 182, 1055-61.
Pre
senta
tionA
MC
.pp
tx
28
• Double blind, RCT, placebo-controlled
• 220 patients, 23 sites
• Validated, previously published sham
• Patients were not on OAB drugs during the study
• Voiding diaries and QoL measures
• Intent-to-treat analysis
SUmiT Trial – UPC vs. Sham
28
Peters, K.M., Carrico, D.J., Perez-Marrero, R.A., Khan, A.U., Wooldridge, L.S., Davis, G.L., & and MacDiarmid, S.A. (2010). Randomized trial of
percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the
SUmiT Trial. J Urol, 183, 1438–1443.
Pre
senta
tionA
MC
.pp
tx
30
SUmit Results
• Statistically significantly better outcome
compared to sham for:
• Urinary urgency (p=0.003)
• Urinary frequency (p<0.001)
• Urinary urge incontinence (p=0.02)
• No serious adverse events or device
malfunctions
30
Peters, K.M., Carrico, D.J., Perez-Marrero, R.A., Khan, A.U., Wooldridge, L.S., Davis, G.L., & and MacDiarmid, S.A. (2010). Randomized trial of
percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the
SUmiT Trial. J Urol, 183, 1438–1443.
Pre
senta
tionA
MC
.pp
tx
31
SUmiT Trial conclusion
• Urgent PC is superior to sham,
• Effect is not due to placebo effect
31
Peters, K.M., Carrico, D.J., Perez-Marrero, R.A., Khan, A.U., Wooldridge, L.S., Davis, G.L., & and MacDiarmid, S.A. (2010). Randomized trial of
percutaneous tibial nerve stimulation versus sham efficacy in the treatment of overactive bladder syndrome: results from the
SUmiT Trial. J Urol, 183, 1438–1443.
Pre
senta
tionA
MC
.pp
tx
32
STEP Study: 36 Months follow-up
• Sustained Therapeutic Effect of Percutaneous Tibial
Nerve Stimulation
• Subjects were participants in the SUmiT trial
• Multi-center, randomized, double-blind
• 29 subjects through 36 months
• Voiding Diary and OAB-q questionnaires
• Evaluation of long-term therapy efficacy
32
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
33
STEP Study - Results
• 29 subjects completed tapering protocol and followed
up through 36 months
• Subjects received 1 PTNS treatments per month
• Sustained significant efficacy and safety of PTNS for
OAB demonstrated
• No treatment related adverse events
33
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
34
STEP Study – 36 Months
34
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
35
STEP Study – 36 Months
35
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
36
STEP Study – 36 Months
36
Mean number of treatments per month
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
37
STEP Study – 36 Months
37
OAB-q HRQoL and Symptom Severity Scores by Follow-up Visit ITT-
LVCF n=50 (p<0.0001)
Peters, K., Carrico, D., Wooldridge, L., Miller, C., & MacDiarmid, S. (2013). Percutaneous tibial nerve stimulation (PTNS) for the long-term treatment
of overactive bladder: Three-year results of the STEP Study. J Urol, 189(6), 2194-2201.
Pre
senta
tionA
MC
.pp
tx
38
• Retrospective, single-site
• 141 female refractory OAB patients
When do patients respond?
38
Symptom
Weeks to
improvement
(median)
Weeks to
improvement
(range)
Percent
patients w/ late
response
(> 8 txs)
Nighttime Voiding 5 2-12 9.9%
Frequency 7 2-12 8.1%
Urgency 6 2-12 18%
Urge
Incontinence
6 2-12 18.6%
Leong, F.C., et al. (2011). Posterior tibial nerve stimulation in patients who have failed anticholinergic therapy: Efficacy and time to response.
Female Pelvic Med Reconstr Surg, 17(2), 74-5.
Pre
senta
tionA
MC
.pp
tx
39
• Comparison of cost-effectiveness between PTNS and
sacral nerve stimulation during 2 years
• The costs were $4,867 and $24,342 for PTNS and SNS,
with 71% and 90% subjective cure rates
• An incremental cost-effectiveness ratio of $99,872 when
staying on therapy was assessed.
• “PTNS and SNS are both safe, effective neuromodulation
therapies for OAB. In this economic model PTNS had
substantially lower cost.”
Cost-effectiveness: PTNS versus SNS
39
Martinson, M., MacDiarmid, S. & Black, E. (2013). Cost of Neuromodulation Therapies for Overactive Bladder: Percutaneous tibial nerve stimulation Versus
Sacral Nerve Stimulation. J Urol, 189(6), 210-216.
Pre
senta
tionA
MC
.pp
tx
40
AMC data
Phase 1
• Drug therapy combined with behavioral therapy
• Drug therapy
Phase 2
• PTNS
• Botox
Phase 3
• Botox
Phase 4
• Bladder augmentation
Pre
senta
tionA
MC
.pp
tx
41
Patient characteristics
• 2012 – 2013
• N = 85 in 2 locations (Amsterdam and Utrecht)
• Previous use of antimuscarinics: 80%
• Previous pelvic physiotherapy: 50%
• Concomitant stress incontinence: 40%
Pre
senta
tionA
MC
.pp
tx
42
Outcome of PTNS
Number of treatments:
Response after first 12 weeks:
• No response = 15/80 = 19%
• Positive response: 39/80 = 49%
• Complete response: 26/80 = 33%
Response at end of therapy:
• No response = 25/80 = 31%
• Positive response: 16/80 = 20%
• Complete response: 39/80 = 49%
Pre
senta
tionA
MC
.pp
tx
43
• Includes 16 studies, 940 total patients
• Subjective success rate of 61.4% (95% CI 53-72%)
• Objective success rate of 60.6% (95% CI 84-75%)
• Statistically superior to Sham [RR 7.02 CI 1.69 – 29.17]
• No significant differences in the change in bladder diary
parameters compared to antimuscarinics; PTNS
associated with a better side-effect profile
Meta-Analysis – Burton
43
Burton, C., Saija, A., Latthe, P.M. (2012). Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder:
A systematic review and meta-analysis. Neurourol Urodyn, 31, 1206-16.
Pre
senta
tionA
MC
.pp
tx
44
Includes 7 studies, 244 patients
71% of patients improved
Meta-Analysis - MacDiarmid
44
Criteria Mean
Improvement
Patients Studie
s
p-value
Daytime Voids 23% 244 7 P<0.001
Nighttime Voids 41% 151 5 P<0.002
Voiding Volume 43% 182 5 P<0.001
Incontinence
Episodes
45% 167 4 p=0.023
I-QoL 17% 122 3 P=0.033
MacDiarmid, S.A., & Staskin, D.R. (2009). Percutaneous tibial nerve stimulation (PTNS): A literature-based assessment.
Curr Bld Dysf Rept, 4, 29-33.
Pre
senta
tionA
MC
.pp
tx
45
Take home message
•PTNS based on sound principle
•Approach of the posterior tibial nerve feasible for clinical application
•Outpatient procedure easy to do
•Level 1A proven efficacy in OAB !