BoNTA for OAB
Noam D. Kitrey, MD, FECSM
Dept. of urology, Sheba medical center, ISRAEL
Chairman of the EAU UroTrauma guidelines panel
Financial and Other Disclosures
• Off-label use of drugs, devices, or other agents: None
• Data from IRB-approved human research is not presented
• I have no financial interests or relationships to disclose
1897 First isolation of
Botulinum toxin by van Ermengem
1960 First clinical use
(Dr. Alan Scott for strabismus)
2011 FDA approval - OnaBoNTA for
NDO
2013 FDA approval - OnaBoNTA for
refractory iOAB
2013 Nobel prize for Prof. James Rothman (Yale university) – BoNT mechanism of action
2015 AUA/SUFU guidelines:
OnaBoNTA (100u) as third-line treatment for refractory
OAB (standard, GrB)
1999 BTX-A into detrusor of NDO first
presented ICS meeting (Stöhrer and Schurch) 21 patients with SCI
onabotulinumtoxinA (Botox)
and
abobotulinumtoxinA (Dysport)
• different formulations
• cannot be considered generic equivalents due to different isolation, manufacturing, and stabilisation processes
BoNTA
SNARE
proteins
Synaptobrevin
(VAMP)
SNAP-25
Syntaxin
SYNAPTIC CLEFT
PRE-SYNAPSE
Receptor requires
SNARE complex for membrane
expression
2. Vesicle and terminal
membranes fuse
3a. Receptors delivered to membrane
insertion sites
3b. Neurotransmitter released
4. Mediators (e.g. SP) bind to
inserted receptors
1. SNARE proteins form
a complex
Adapted from Arnon et al. JAMA. 2001;285:1059–70.
Mechanism of action
Dmochowski et al. 2010 J Urol
• phase 2, multicenter, randomized, double-blind study
• 313 patients with idiopathic overactive bladder and urinary
urgency incontinence
• 50, 100, 150, 200 or 300 U intradetrusor onaboNTA or placebo
Dmochowski et al. 2010 J Urol
Dmochowski et al. 2010 J Urol
• A dose of 100 U appropriately balances
– symptom benefits with
– post-void residual urine volume
Week 2 Week 6 Week 12
Mea
n c
han
ge
fro
m b
asel
ine
(ep
iso
des
/day
) EMBARK study (phase III)
EMBARK Study Nitti VW et al. J Urol 2013 189 6):2186-93
Baseline values
Placebo: 5.39/day
BOTOX® 100 U: 5.49/day
0
–1.22
–0.95
–2.85** –3.11**
–2.80**
Placebo (n = 548)
BOTOX® 100 U (n = 557)
At week 12, BOTOX® led to a 51% reduction from baseline in UI episodes versus 18% with placebo (p < 0.001)
–1
–2
–3
–4
**p < 0.001 vs placebo.
–1.35 –1.40 –1.23
–2.89**
–3.56** –3.30**
-5
-4
-3
-2
-1
0
Week 2 Week 6 Week 12
Mea
n c
han
ge
fro
m b
asel
ine
(ep
iso
des
/day
) EMBARK study (phase III)
EMBARK Study Nitti VW et al. J Urol 2013 189 6):2186-93
At week 12, BOTOX® led to a 37% reduction from baseline in daily urgency episodes versus 15% with placebo (p < 0.001)
Baseline values
Placebo: 8.31/day
BOTOX® 100 U: 8.82/day
**p < 0.001 vs placebo.
Placebo (n = 548)
BOTOX® 100 U (n = 557)
EMBARK study (phase III)
EMBARK Study Nitti VW et al. J Urol 2013 189 6):2186-93
76%
Patients with 50% or 75% decrease in urinary incontinence
31.0 17.7 60.5 46.0 0
10
20
30
40
50
60
70 75% reduction
Patients with 100% decrease in urinary incontinence (‘DRY’)*
8.4 27.1 0
10
20
30
Column1
Pat
ien
ts (
%)
Pat
ien
ts (
%)
50% reduction
Placebo
(n = 548)
BOTOX® 100 U
(n = 557)
BOTOX®
100 U
(n = 557)
Placebo
(n = 548)
Placebo
(n = 548)
BOTOX®
100 U
(n = 557)
EMBARK study (phase III)
EMBARK Study Nitti VW et al. J Urol 2013 189 6):2186-93
The median duration of response after BOTOX® treatment,
based on patient request for re-treatment,
was 166 days (~6 months)
Platinum Priority – IncontinenceEditorial by Stephan Madersbacher on pp. 257–259 of this issue
Onabotul inum toxinA 100 U Sign if icant ly Im proves Al l Idiopathic
Overact ive Bladder Sym ptom s and Qual i t y of Li fe in Pat ients w ith
Overact ive Bladder and Ur inary Incont inence: A Random ised,
Double-Bl ind, Placebo-Cont rol led Tr ial
Christopher Chapple a,*, Karl-Dietr ich Sievert b, Scott MacDiarmid c, Vik Khullar d,
Piotr Radziszewski e, Christopher Nardo f, Catherine Thompson g, Jihao Zhou f,
Cornelia Haag-Molkenteller f
a Royal Hallamshire Hospital, Sheffield, UK; b University of Tuebingen, Tuebingen, Germany; c Alliance Urology Specialists, Greensboro, NC, USA; d Imperial
College, London, UK; e Department of Urology, Medical University of Warsaw, Warsaw, Poland; f Allergan, Inc., Irvine, CA, USA; g Allergan Ltd., Marlow, UK
EU RO PEA N U RO L O G Y 6 4 ( 2 0 1 3 ) 2 4 9 – 2 5 6
av a i l ab l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e: w w w .eu r o p ean u r o l o g y .co m
Art icle info
Art icle history:
Accepted April 1, 2013
Published online ahead of
pr int on Apri l 10, 2013
Keywords:
Botulinum toxin
OnabotulinumtoxinA
Overact ive bladder
Urinary incont inence
Abst ract
Background: Overact ive bladder (OAB) syndrome w ith urinary incont inence (UI) is prevalent
in the populat ion and impairs health-related quality of l i fe (HRQOL).
Object ive: To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA
(BOTOX1 , Allergan, Inc.) treatment in pat ients w ith OAB w ith UI.
Design, sett ing, and par t i cipants: Thispivotal,mult icentre,double-blind,randomised,placebo-
controlled, phase 3 study enrolled patients w ith idiopathic OAB w ith 3 urgency UI episodes
over 3 d and 8 micturit ions per day w ho w ere inadequately managed by anticholinergics.
Intervent ion: OnabotulinumtoxinA at a 100 U dose (n = 277) or placebo (n = 271), adminis-
tered as 20 intradet rusor inject ions of 0.5 ml.
Outcome measurements and stat ist ical analysis: Co–primary end points w ere change from
baseline in the number of UI episodes per day and proport ion of pat ients reporting posit ive
treatment response on the treatment benefi t scale (TBS) at w eek 12. Addit ional end points
included other OAB symptoms (episodes of urinary urgency incontinence, micturit ion, urgency,
and nocturia) and HRQOL (Incontinence Quality of Life [I-QOL], King’s Health Quest ionnaire
[KHQ]).Safety assessments included adverse events (AEs),postvoid residual (PVR) urine volume,
and init iat ion of clean intermittent catheterisat ion (CIC).
Results and limitat ions: Onabotulinumtox inA signifi cant ly decreased UI episodes per day at
w eek 12 ( 2.95 for onabotulinumtoxinA versus 1.03 for placebo; p < 0.001). Reduct ions
from baseline in all other OAB symptoms w ere also significant ly greater follow ing onabotu-
l inumtoxinA compared w ith placebo ( p 0.01). Pat ients perceived a significant improvement
in their condit ion, as measured by patients w ith a posit ive treatment response on the TBS
(62.8% for onabot ulinumtoxinA versus 26.8% for placebo; p < 0.001). Clinically meaningful
improvement s from baseli ne in all I-QOL and KHQ mult i-i tem domains ( p < 0.001 versus
placebo) indicated posit ive impact on HRQOL. AEs w ere mainly local ised to the urinary tract.
Mean PVR w as higher in the onabotul inumtoxinA group (46.9 ml versus 10.1 ml at w eek 2;
p < 0.001); 6.9%of onabotulinumtoxinA patients versus 0.7%of placebo patients init iated CIC.
Conclusions: OnabotulinumtoxinA 100 U w as w el l tolerated and dem onstrated signifi cant
and clinically relevant improvement s in all OAB symptoms, pat ient- reported benefi t, and
HRQOL in pat ients inadequat ely managed by anticholinergi cs.
Tr ial registrat ion: ClinicalTrials.gov: NCT00910520.
# 2013 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
* Correspondi ng author. Royal Hallamshire Hospital, Room H26, H-Floor, Glossop Road, Sheffield,
GB-S10 2JF, UK. Tel. +44 0 114 271 3048; Fax: +44 0 114 279 7841.
E-mail address: [email protected] (C. Chapple).
0302-2838/$ – see back matter # 2013 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
ht tp://dx.doi .org/10.1016/j.eururo.2 013.04.001
Chapple C et al. Eur Urol 2013
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Tw o-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e : w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulat ion
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are ut i l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and par t icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All r ights reserved.
Platinum Priority – IncontinenceEditorial by Stephan Madersbacher on pp. 257–259 of this issue
Onabotul inum toxinA 100 U Sign if icant ly Im proves Al l Idiopathic
Overact ive Bladder Sym ptom s and Qual i t y of Li fe in Pat ients w ith
Overact ive Bladder and Ur inary Incont inence: A Random ised,
Double-Bl ind, Placebo-Cont rol led Tr ial
Christopher Chapple a,*, Karl-Dietr ich Sievert b, Scott MacDiarmid c, Vik Khullar d,
Piotr Radziszewski e, Christopher Nardo f, Catherine Thompson g, Jihao Zhou f,
Cornelia Haag-Molkenteller f
a Royal Hallamshire Hospital, Sheffield, UK; b University of Tuebingen, Tuebingen, Germany; c Alliance Urology Specialists, Greensboro, NC, USA; d Imperial
College, London, UK; e Department of Urology, Medical University of Warsaw, Warsaw, Poland; f Allergan, Inc., Irvine, CA, USA; g Allergan Ltd., Marlow, UK
EU RO PEA N U RO L O G Y 6 4 ( 2 0 1 3 ) 2 4 9 – 2 5 6
av a i l ab l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e: w w w .eu r o p ean u r o l o g y .co m
Art icle info
Art icle history:
Accepted April 1, 2013
Published online ahead of
pr int on Apri l 10, 2013
Keywords:
Botulinum toxin
OnabotulinumtoxinA
Overact ive bladder
Urinary incont inence
Abst ract
Background: Overact ive bladder (OAB) syndrome w ith urinary incont inence (UI) is prevalent
in the populat ion and impairs health-related quality of l i fe (HRQOL).
Object ive: To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA
(BOTOX1 , Allergan, Inc.) treatment in pat ients w ith OAB w ith UI.
Design, sett ing, and par t i cipants: Thispivotal,mult icentre,double-blind,randomised,placebo-
controlled, phase 3 study enrolled patients w ith idiopathic OAB w ith 3 urgency UI episodes
over 3 d and 8 micturit ions per day w ho w ere inadequately managed by anticholinergics.
Intervent ion: OnabotulinumtoxinA at a 100 U dose (n = 277) or placebo (n = 271), adminis-
tered as 20 intradet rusor inject ions of 0.5 ml.
Outcome measurements and stat ist ical analysis: Co–primary end points w ere change from
baseline in the number of UI episodes per day and proport ion of pat ients reporting posit ive
treatment response on the treatment benefi t scale (TBS) at w eek 12. Addit ional end points
included other OAB symptoms (episodes of urinary urgency incontinence, micturit ion, urgency,
and nocturia) and HRQOL (Incontinence Quality of Life [I-QOL], King’s Health Quest ionnaire
[KHQ]).Safety assessments included adverse events (AEs),postvoid residual (PVR) urine volume,
and init iat ion of clean intermittent catheterisat ion (CIC).
Results and limitat ions: Onabotulinumtox inA signifi cant ly decreased UI episodes per day at
w eek 12 ( 2.95 for onabotulinumtoxinA versus 1.03 for placebo; p < 0.001). Reduct ions
from baseline in all other OAB symptoms w ere also significant ly greater follow ing onabotu-
l inumtoxinA compared w ith placebo ( p 0.01). Pat ients perceived a significant improvement
in their condit ion, as measured by patients w ith a posit ive treatment response on the TBS
(62.8% for onabot ulinumtoxinA versus 26.8% for placebo; p < 0.001). Clinically meaningful
improvement s from baseli ne in all I-QOL and KHQ mult i-i tem domains ( p < 0.001 versus
placebo) indicated posit ive impact on HRQOL. AEs w ere mainly local ised to the urinary tract.
Mean PVR w as higher in the onabotul inumtoxinA group (46.9 ml versus 10.1 ml at w eek 2;
p < 0.001); 6.9%of onabotulinumtoxinA patients versus 0.7%of placebo patients init iated CIC.
Conclusions: OnabotulinumtoxinA 100 U w as w el l tolerated and dem onstrated signifi cant
and clinically relevant improvement s in all OAB symptoms, pat ient- reported benefi t, and
HRQOL in pat ients inadequat ely managed by anticholinergi cs.
Tr ial registrat ion: ClinicalTrials.gov: NCT00910520.
# 2013 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
* Correspondi ng author. Royal Hallamshire Hospital, Room H26, H-Floor, Glossop Road, Sheffield,
GB-S10 2JF, UK. Tel. +44 0 114 271 3048; Fax: +44 0 114 279 7841.
E-mail address: [email protected] (C. Chapple).
0302-2838/$ – see back matter # 2013 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
ht tp://dx.doi .org/10.1016/j.eururo.2 013.04.001
Chapple C et al. Eur Urol 2013
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Tw o-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e : w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulat ion
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are ut i l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and par t icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All r ights reserved.
• 56 Adult OAB studies
• 16 Level 1+2 studies (1380 pts.)
• 40 level 3 studies (2673 pts.)
Allergan data
93.5% Not on CIC
Did not initiate CIC
Used CIC for ≤ 6 weeks
Used CIC for > 6 and ≤ 12 weeks
Used CIC for > 12 and ≤ 18 weeks
Used CIC for > 18 and ≤ 24 weeks
Used CIC for > 24 weeks
2.5%
1.3%
0.4% 1.4%
0.9% 6.5% CIC = 6.5% (36/552 patients)
Patients requiring CIC at any point during treatment cycle
• Greater symptomatic and urodynamic improvements with 200
IU compared with 100 IU.
• At the cost of a greater ISC frequency that was 24–31% for 200
IU compared with 7–10% for 100 IU ( p < 0.001)
• prospective, multicenter, long-term (3.5-year) study
• 131 centers
• 839 pts entered – 430 completed extension study
Nitti at al. 2016 J Urol
Nitti at al. 2016 J Urol
Nitti at al. 2016 J Urol
Nitti at al. 2016 J Urol
• Durable and meaningful improvements in urinary symptoms and QOL
• The median duration of effect was 7.6 months
• The rate of de novo catheterization
– after the first treatment was 4.0%
– 0.6% to 1.7% after subsequent treatments
Nitti at al. 2016 J Urol
Nitti at al. 2016 J Urol
Nitti at al. 2016 J Urol
Carlson et al. 2017 Can J Urol
• “Real world” study
• 81 patients with repeated injections
• No difference between first and repeat injections in
outcomes and safety
• ~50% became dry
• Significant improvements in PRO
Carlson et al. 2017 Can J Urol
• ~10% remain on anti-cholinergics
• Some use them to “bridge the gap”
• 16.7% of SIC in de-novo group
• Double-blind BoNTA Vs. Solifenacin
• 472 screened but only 118+113 completed 6m
Visco et al. N Eng J Med 2012
Visco et al. N Eng J Med 2012
Visco et al. N Eng J Med 2012
Amundsen CL et al. 2016 JAMA
• ROSETTA trial
• Multicenter, open-label, randomized trial
• 2012-2015 at 9 US medical centers
• 381 women with refractory urgency urinary
incontinence
• 200u of OnaBotNT-A Vs. SMN
• 6 months follow-up
Amundsen CL et al. 2016 JAMA
Amundsen CL et al. 2016 JAMA
Amundsen CL et al. 2016 JAMA
• OnaBoNTA provided a small but statistically significant greater
reduction in episodes of UUI than sacral neuromodulation
• No significant difference for quality of life or for the subscales
for treatment preference, convenience, or adverse effects
• OnaBoNTA increased the risk of urinary tract infections and
need for self-catheterizations
Amundsen CL et al. 2018 Euro Urol
• planned 24-mo extension trial compared efficacy,
AEs, and satisfaction with therapy in women
randomized to either SNM or BTX 200 units
• Cross-over permissible
• BotNT re-injections permissible
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Two-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e: w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulation
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are uti l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and part icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Tw o-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e : w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulat ion
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are ut i l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and par t icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All r ights reserved.
Amundsen CL et al. 2018 Euro Urol
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Two-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e: w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulation
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are uti l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and part icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Tw o-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e : w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulat ion
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are ut i l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and par t icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All r ights reserved.
Amundsen CL et al. 2018 Euro Urol
• sustained and similar reductions in mean daily UUIE
• BTX more likely complete resolution of UUIE in the first 6m
• BTX had higher satisfaction and treatment endorsement throughout the 24m
• No significant difference QoL measures, global assessment of improvement, or adverse effects subscales.
• The use of UUI medications or the alternate trial therapy was comparable
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Two-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e: w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulation
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are uti l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and part icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All rights reserved.
Platinum Priority – Female Urology – IncontinenceEditorial by Bertil F.M. Blok on pp. 74–75 of this issue
Tw o-Year Outcom es of Sacral Neurom odulat ion Versus
Onabotul inum toxinA for Refractory Urgency Ur inary
Incont inence: A Random ized Tr ial
Cindy L. Amundsen a,*, Yuko M. Komesu b, Christopher Chermansky c, W. Thomas Gregory d,
Deborah L. Myerse, Emily F. Honeycutt f, Sandip P. Vasavada g, John N. Nguyen h,
Tracey S. Wilson i, Heidi S. Harvie j, Dennis Wallace f,
for the Pelvic Floor Disorders Network
a Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA; b Department of Obstetrics and Gynecology, University of New
Mexico, Albuquerque, New Mexico, USA; c Department of Urology, University of Pittsburgh, Pennsylvania, USA; d Department of Obstetrics and Gynecology,
Oregon Health & Science University, Portland, Oregon, USA; e Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA;f Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, North Carolina, USA; g Department of Urology, Cleveland Clinic,
Cleveland, Ohio, USA; h Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, California, USA; i Department of Urology, University of
Alabama at Birmingham, Birmingham, Alabama, USA; j Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
EU RO PEA N U RO L O GY 7 4 ( 2 0 1 8 ) 6 6 – 7 3
av a i l a b l e a t w w w .sc i en ced i r ec t . co m
j o u r n a l h o m ep ag e : w w w .eu r o p ean u r o l o g y .co m
Ar t icle info
Art icle history:
Accepted February 12, 2018
Associate Editor :
J.-N. Cornu
Stat ist ical Editor :
Andrew Vickers
Keywords:
Sacral neuromodulat ion
OnbotulinumtoxinA
InterStim
Urgency urinary incontinence
Botox
Abst ract
Background: Urgency urinary incont inence (UUI) is a chronic condit ion for w hich sacral
neuromodulat ion (SNM) (InterSt im/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/
Allergan) are ut i l ized. These therapies have not been compared over extended t ime.
Object ive: To compare UUI episodes (UUIE) over 24 mo follow ing SNM or BTX.
Design, sett ing, and par t icipants: Mult icenter, open-label, randomized, extension trial
(February 2012–July 2016) at nine US medical centers involving 386 w omen w ith 6
UUIE over 3 d inadequately managed by medicat ions. Part icipants w ere clinical re-
sponders to treatment : 50%reduct ion in UUIEs after SNM placement or 1 mo post BTX.
Intervent ion: SNM (n = 194) versus 200 U BTX (n = 192). SNM reprogrammings occurred
throughout the 24 mo. After 6 mo, tw o addit ional BTX inject ions w ere allow ed.
Outcome measurements and stat ist ical analysis: Primary outcome: change in mean
daily UUIE over 24 mo. Secondary outcomes: no UUIE, 75%and 50%UUIE reduct ion;
Overact ive Bladder Quest ionnaire Short Form; Urinary Distress Inventory short form;
Incont inence Impact Quest ionnaire; Pat ient Global Impression of Improvement; Over-
act ive Bladder Sat isfact ion of Treatment Quest ionnaire; and adverse events (AEs).
Primary analysis used a linear mixed model.
Results and limitat ions: Outcome data w ere available for 260/298 (87%) clinical re-
sponders. No difference in decreased mean UUIE was found over 24 mo ( 3.88 vs 3.50
episodes/d,95% confidence interval [CI] = 0.14–0.89; p = 0.15), w ith no differences in
UUI resolut ion, 75%or 50%UUIEreduct ion. BTX group maintained higher sat isfact ion
(mean difference = 9.14, 95%CI = 14.38– 3.90; p < 0.001), t reatment endorsement
(mean difference = 12.16, 95% CI = 17.7– 6.63; p < 0.001) through 24 mo. Other
secondary measures did not differ. Recurrent urinary tract infect ions (UTIs) w ere higher
* Corresponding author. 5324 McFarland Drive, Suite 310, Durham , North Carolina 27707, USA.
Tel. +1 919 401 1006; Fax: +1 919 401 1033.
E-mail address: [email protected] (C.L. Amundsen).
ht tps://doi.org/10.1016/j.eururo.2018.02.011
0302-2838/© 2018 European Associat ion of Urology. Published by Elsevier B.V. All r ights reserved.
Based on
• 9 RCT placebo controlled
• 4 RCT active groups
• 35 Observational studies
Limitations
• Short follow-up in most studies
• Variability in
– doses
– injection sites
– adverse events
Take Home Messages
• BoNTA significantly improves refractory iOAB symptoms
• Improves quality of life
• Simple (mostly office) procedure
• CIC 6-10% (for 100 units)
• Increased UTI risk
• Sustained efficacy and tolerability over repeated
treatments
BoNTA for OAB
Noam D. Kitrey, MD, FECSM
Dept. of urology, Sheba medical center, ISRAEL
Chairman of the EAU UroTrauma guidelines panel
Top Related