2015 Update on pelvic floor dysfunction: Bladder pain syndrome

Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545−1553.

The diagnosis of IC/BPS can be challenging due to a wide spectrum of symptoms, physical examination findings, and clinical test responses. The AUA developed its diagnostic and treatment guidelines mostly based on expert opinion, but they do provide a framework to help clinicians determine whether or not treatment for IC/BPS is warranted. The primary principles for evaluation are presented in FIGURE 1.

7,8

It is important to establish baseline voiding symptoms and pain levels with objective, validated instruments, including a voiding diary (FIGURE 2)⁹ and such patient questionnaires as the O’Leary Sant Interstitial Cystitis Index (ICSI; FIGURE 3).¹⁰ Characteristic IC/BPS voiding frequency is 10 or more times per day (to relieve pain, not to relieve a fear of wetting, which would be expected in a patient with overactive bladder).⁸ The ICSI questionnaire
should be used primarily to establish baseline symptoms, not as a diagnostic tool. A score higher than 8 has been used as inclusion criteria for therapeutic trials, however.¹¹

FIGURE 2 Voiding diary9

FIGURE 3 O’Leary Sant Interstitial Cystitis Index10

It is unnecessary to primarily perform cystoscopy or urodynamics, as there are no agreed-upon diagnostic criteria for these modalities for IC/BPS. They may be considered, however, if the patient does not respond to first- and second-line therapies. Additionally, potassium sensitivity testing is painful and, in view of the paucity of benefits, the risk/benefit ratio is too high to recommend for clinical care.

Treatment: Conservative first
The treatment for IC/BPS should start with more conservative therapy (including behavioral management and physical therapy). If symptom control is inadequate, other modalities should be employed. Behavioral modifications should include:

As noted in FIGURE 1, first make sure that patients do not have a urinary tract infection. If culture results are negative and other criteria fit, consider the diagnosis of IC/BPS and offer therapies as outlined in the ­treat‑
ment algorithm (FIGURE 4).⁷ Repeated 
treatment for negative results of urine cultures in patients with frequency, urgency, and bladder pain can lead to unnecessary antibiotics and delayed treatment of IC/BPS.

7

Treatments in FIGURE 4 are ordered from most to least conservative, and initial treatment depends on symptom severity, 
clinician judgment, and patient preference. If at any point in the patient’s care the diagnosis is questioned or treatments have been ineffective, referral to a specialist, including urogynecology or urology, may be appropriate.

Managing pain
Pain management is an important component at all levels of therapy, and pharmacologic pain management principles for 
IC/BPS should be similar to those for management of other chronic pain states. Options primarily include nonsteroidal anti-
inflammatory drugs (NSAIDs) and urinary analgesics (pyridium). The use of narcotics presents the risks of tolerance and dependence. If their use is necessary, all narcotic prescriptions must come from a single source and should be used as a component of multimodality therapy to minimize narcotic use.

Oral PPS is FDA approved for relief of bladder pain associated with IC/BPS

Nickel JC, Herschorn S, Whitmore KE, et al. Pentosan polysulfate sodium for treatment of interstitial cystitis/ 
bladder pain syndrome: insights from a randomized, double-blind, placebo-controlled study. J Urol. 2015;193(3):857−862.

In this multicenter, double-blind, randomized, placebo-controlled study, investigators evaluated the efficacy and tolerability of a decreased dose of PPS (100 mg daily) versus the current established dose (100 mg TID) in patients with IC/BPS.

Details of the study
A total of 368 participants (85.6% of whom were women) aged 18 to 78 years with 
questionnaire-diagnosed IC/BPS and no urinary tract infection for at least 6 months before screening were randomly assigned by a computer-generated randomization schedule in a 1:1:1 ratio to PPS 100 mg 3 times per day (FDA-approved dose), PPS 100 mg daily, or matching placebo. Safety assessments were performed at prespecified time points over 24 weeks. The primary efficacy endpoint was defined as a 30% reduction in ICSI total score. The study was powered to detect a 15% difference in the proportion of responders if there were 200 patients per treatment arm.

There was an interim analysis performed due to slow recruitment that led to early study termination, but all initially enrolled participants were included in the intention to treat analysis. Of the 368 patients, 162 (44%) withdrew from the study, with equal numbers in each arm. The treatment response rate was 40.7% for patients assigned to placebo, 39.8% for patients treated with PPS 100 mg once daily, and 42.6% for those treated with PPS 100 mg 3 times per day. These rates were not significantly different between groups.

Adverse events were equal between groups and included bladder pain, nausea,
headache, and exacerbation of IC/BPS 
symptoms. Gastrointestinal events led to the withdrawal of 10% of participants in the placebo group and 11% to 13% in the PPS 
groups. No clinically meaningful change was noted in laboratory tests, vital signs, or physical examination.

Study expands data on oral PPS
This was a multicenter, double-blind, randomized study of adults diagnosed with 
IC/BPS based on symptoms. Earlier studies of PPS efficacy, which provided the data for FDA approval of oral PPS, employed strict cystoscopic criteria for IC/BPS diagnosis.¹² Although the study was terminated early due to low recruitment and there was a high drop-out rate, there still was a large number of patients in each treatment arm. Furthermore, although the responder rate did not differ between groups, this may have 
been due to lack of power at the recruited numbers.

This study is an important glimpse into the use of oral PPS in a broad population of patients with bladder pain, urgency, frequency, and nocturia. It further emphasizes the need for improved diagnostic criteria to provide individualized, efficacious treatment for patients with IC/BPS.

What this EVIDENCE means for practice
Clinicians should continue to recommend conservative treatments for IC/BPS, including behavioral modifications, stress management, and manual physical therapy techniques prior to initiation of medications. Oral PPS may still be considered as a possible second-line therapy or as multimodal therapy for patients with IC/BPS.

Botulinum toxin-A with hydrodistention shows short-term efficacy as advanced therapy

In this multicenter, randomized, double-blind, placebo-controlled trial in patients with IC/BPS refractory to conventional treatment, investigators evaluated the efficacy and tolerability of hydrodistention plus suburothelial injections of onabotulinum toxin A (BoNT-A; Botox).

Details of the study
Sixty patients (86.7% female) aged 20 to 82 who had failed 6 months of conventional treatment for IC/BPS were enrolled. In this particular study, diagnosis was established based on symptoms and glomerulations on cystoscopy during hydrodistension. Patients were included if they had failed 2 prior treatment modalities for IC/BPS. Participants completed a baseline voiding diary, ICSI questionnaire, and visual analogue scale (VAS) for patient self-reported pain. All patients also received video-urodynamic testing prior to therapy.

Eligible patients were randomly assigned in a 2:1 ratio to either receive 100 units of intradetrusor BoNT-A or injection with normal saline immediately following cystoscopic hydrodistension under general anesthesia. All patients received oral antibiotics for 
7 days after therapy. Follow up was performed at 2, 4, and 8 weeks after treatment, with additional voiding diaries, symptom questionnaires, and VAS scores collected. At 8 weeks, a urodynamic study was performed.

The primary endpoint was reduction of pain on VAS score at the 8-week follow-up. With 60 participants, researchers had 85% power to detect a difference of 1.5 points on the VAS score between groups. Secondary outcomes included a composite global response assessment (GRA), ICSI scores, voiding diary parameters, and urodynamic findings.

No differences were noted in baseline measurements between the 2 groups except for VAS score, which was higher at baseline in the BoNT-A group (P = .056).

At 8 weeks, the BoNT-A group showed a significantly greater reduction than the saline group in the mean (SD) pain score (-2.6 [2.8] vs -0.9 [2.2], respectively; P = .021). Mean (SD) cystometric bladder capacity also increased significantly in the BoNT-A versus saline group (67.8 [164.3] vs -45.4 [138.5]; 
P = .020). Other secondary outcomes, including ICSI score, GRA, and functional bladder capacity as noted on voiding diary, improved significantly from baseline in both groups at 8 weeks.

Adverse events included dysuria, hematuria, urinary tract infection, and retention. There was a higher rate of dysuria noted in the BoNT-A compared with the saline group (40% vs 5%, respectively) at 8 weeks. There was only 1 urinary tract infection in each group, and only 1 patient had retention in the BoNT-A group, although study criteria for retention or need for self-catheterization was not provided.

Short-term efficacy, 
but more data needed
This was a well-designed trial evaluating the addition of BoNT-A to hydrodistension in a population of patients with refractory 
IC/BPS. The participants were mostly women and relevant to a gynecologic population. When utilized for patients with overactive bladder, 100 units of intradetrusor injections of BoNT-A has rates of urinary tract infection and retention of approximately 33% and 5%, respectively.¹³ Patients with IC/BPS undergoing this procedure should be counseled about these possible adverse effects. Furthermore, with a relatively short 8-week follow-up period, this study cannot be used to make any comments on long-term efficacy of this procedure.

What this EVIDENCE means for practice
Although BoNT-A is not currently FDA approved for the treatment of IC/BPS, it is listed as fourth-line therapy for women with this condition. If initial therapies fail, it is appropriate to refer patients to a specialist, including a urogynecologist or urologist, where they may discuss BoNT-A therapy with or without hydrodistension.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545−1553.

The diagnosis of IC/BPS can be challenging due to a wide spectrum of symptoms, physical examination findings, and clinical test responses. The AUA developed its diagnostic and treatment guidelines mostly based on expert opinion, but they do provide a framework to help clinicians determine whether or not treatment for IC/BPS is warranted. The primary principles for evaluation are presented in FIGURE 1.

7,8

It is important to establish baseline voiding symptoms and pain levels with objective, validated instruments, including a voiding diary (FIGURE 2)⁹ and such patient questionnaires as the O’Leary Sant Interstitial Cystitis Index (ICSI; FIGURE 3).¹⁰ Characteristic IC/BPS voiding frequency is 10 or more times per day (to relieve pain, not to relieve a fear of wetting, which would be expected in a patient with overactive bladder).⁸ The ICSI questionnaire
should be used primarily to establish baseline symptoms, not as a diagnostic tool. A score higher than 8 has been used as inclusion criteria for therapeutic trials, however.¹¹

FIGURE 2 Voiding diary9

FIGURE 3 O’Leary Sant Interstitial Cystitis Index10

It is unnecessary to primarily perform cystoscopy or urodynamics, as there are no agreed-upon diagnostic criteria for these modalities for IC/BPS. They may be considered, however, if the patient does not respond to first- and second-line therapies. Additionally, potassium sensitivity testing is painful and, in view of the paucity of benefits, the risk/benefit ratio is too high to recommend for clinical care.

Treatment: Conservative first
The treatment for IC/BPS should start with more conservative therapy (including behavioral management and physical therapy). If symptom control is inadequate, other modalities should be employed. Behavioral modifications should include:

As noted in FIGURE 1, first make sure that patients do not have a urinary tract infection. If culture results are negative and other criteria fit, consider the diagnosis of IC/BPS and offer therapies as outlined in the ­treat‑
ment algorithm (FIGURE 4).⁷ Repeated 
treatment for negative results of urine cultures in patients with frequency, urgency, and bladder pain can lead to unnecessary antibiotics and delayed treatment of IC/BPS.

7

Treatments in FIGURE 4 are ordered from most to least conservative, and initial treatment depends on symptom severity, 
clinician judgment, and patient preference. If at any point in the patient’s care the diagnosis is questioned or treatments have been ineffective, referral to a specialist, including urogynecology or urology, may be appropriate.

Managing pain
Pain management is an important component at all levels of therapy, and pharmacologic pain management principles for 
IC/BPS should be similar to those for management of other chronic pain states. Options primarily include nonsteroidal anti-
inflammatory drugs (NSAIDs) and urinary analgesics (pyridium). The use of narcotics presents the risks of tolerance and dependence. If their use is necessary, all narcotic prescriptions must come from a single source and should be used as a component of multimodality therapy to minimize narcotic use.

Oral PPS is FDA approved for relief of bladder pain associated with IC/BPS

Nickel JC, Herschorn S, Whitmore KE, et al. Pentosan polysulfate sodium for treatment of interstitial cystitis/ 
bladder pain syndrome: insights from a randomized, double-blind, placebo-controlled study. J Urol. 2015;193(3):857−862.

In this multicenter, double-blind, randomized, placebo-controlled study, investigators evaluated the efficacy and tolerability of a decreased dose of PPS (100 mg daily) versus the current established dose (100 mg TID) in patients with IC/BPS.

Details of the study
A total of 368 participants (85.6% of whom were women) aged 18 to 78 years with 
questionnaire-diagnosed IC/BPS and no urinary tract infection for at least 6 months before screening were randomly assigned by a computer-generated randomization schedule in a 1:1:1 ratio to PPS 100 mg 3 times per day (FDA-approved dose), PPS 100 mg daily, or matching placebo. Safety assessments were performed at prespecified time points over 24 weeks. The primary efficacy endpoint was defined as a 30% reduction in ICSI total score. The study was powered to detect a 15% difference in the proportion of responders if there were 200 patients per treatment arm.

There was an interim analysis performed due to slow recruitment that led to early study termination, but all initially enrolled participants were included in the intention to treat analysis. Of the 368 patients, 162 (44%) withdrew from the study, with equal numbers in each arm. The treatment response rate was 40.7% for patients assigned to placebo, 39.8% for patients treated with PPS 100 mg once daily, and 42.6% for those treated with PPS 100 mg 3 times per day. These rates were not significantly different between groups.

Adverse events were equal between groups and included bladder pain, nausea,
headache, and exacerbation of IC/BPS 
symptoms. Gastrointestinal events led to the withdrawal of 10% of participants in the placebo group and 11% to 13% in the PPS 
groups. No clinically meaningful change was noted in laboratory tests, vital signs, or physical examination.

Study expands data on oral PPS
This was a multicenter, double-blind, randomized study of adults diagnosed with 
IC/BPS based on symptoms. Earlier studies of PPS efficacy, which provided the data for FDA approval of oral PPS, employed strict cystoscopic criteria for IC/BPS diagnosis.¹² Although the study was terminated early due to low recruitment and there was a high drop-out rate, there still was a large number of patients in each treatment arm. Furthermore, although the responder rate did not differ between groups, this may have 
been due to lack of power at the recruited numbers.

This study is an important glimpse into the use of oral PPS in a broad population of patients with bladder pain, urgency, frequency, and nocturia. It further emphasizes the need for improved diagnostic criteria to provide individualized, efficacious treatment for patients with IC/BPS.

What this EVIDENCE means for practice
Clinicians should continue to recommend conservative treatments for IC/BPS, including behavioral modifications, stress management, and manual physical therapy techniques prior to initiation of medications. Oral PPS may still be considered as a possible second-line therapy or as multimodal therapy for patients with IC/BPS.

Botulinum toxin-A with hydrodistention shows short-term efficacy as advanced therapy

In this multicenter, randomized, double-blind, placebo-controlled trial in patients with IC/BPS refractory to conventional treatment, investigators evaluated the efficacy and tolerability of hydrodistention plus suburothelial injections of onabotulinum toxin A (BoNT-A; Botox).

Details of the study
Sixty patients (86.7% female) aged 20 to 82 who had failed 6 months of conventional treatment for IC/BPS were enrolled. In this particular study, diagnosis was established based on symptoms and glomerulations on cystoscopy during hydrodistension. Patients were included if they had failed 2 prior treatment modalities for IC/BPS. Participants completed a baseline voiding diary, ICSI questionnaire, and visual analogue scale (VAS) for patient self-reported pain. All patients also received video-urodynamic testing prior to therapy.

Eligible patients were randomly assigned in a 2:1 ratio to either receive 100 units of intradetrusor BoNT-A or injection with normal saline immediately following cystoscopic hydrodistension under general anesthesia. All patients received oral antibiotics for 
7 days after therapy. Follow up was performed at 2, 4, and 8 weeks after treatment, with additional voiding diaries, symptom questionnaires, and VAS scores collected. At 8 weeks, a urodynamic study was performed.

The primary endpoint was reduction of pain on VAS score at the 8-week follow-up. With 60 participants, researchers had 85% power to detect a difference of 1.5 points on the VAS score between groups. Secondary outcomes included a composite global response assessment (GRA), ICSI scores, voiding diary parameters, and urodynamic findings.

No differences were noted in baseline measurements between the 2 groups except for VAS score, which was higher at baseline in the BoNT-A group (P = .056).

At 8 weeks, the BoNT-A group showed a significantly greater reduction than the saline group in the mean (SD) pain score (-2.6 [2.8] vs -0.9 [2.2], respectively; P = .021). Mean (SD) cystometric bladder capacity also increased significantly in the BoNT-A versus saline group (67.8 [164.3] vs -45.4 [138.5]; 
P = .020). Other secondary outcomes, including ICSI score, GRA, and functional bladder capacity as noted on voiding diary, improved significantly from baseline in both groups at 8 weeks.

Adverse events included dysuria, hematuria, urinary tract infection, and retention. There was a higher rate of dysuria noted in the BoNT-A compared with the saline group (40% vs 5%, respectively) at 8 weeks. There was only 1 urinary tract infection in each group, and only 1 patient had retention in the BoNT-A group, although study criteria for retention or need for self-catheterization was not provided.

Short-term efficacy, 
but more data needed
This was a well-designed trial evaluating the addition of BoNT-A to hydrodistension in a population of patients with refractory 
IC/BPS. The participants were mostly women and relevant to a gynecologic population. When utilized for patients with overactive bladder, 100 units of intradetrusor injections of BoNT-A has rates of urinary tract infection and retention of approximately 33% and 5%, respectively.¹³ Patients with IC/BPS undergoing this procedure should be counseled about these possible adverse effects. Furthermore, with a relatively short 8-week follow-up period, this study cannot be used to make any comments on long-term efficacy of this procedure.

What this EVIDENCE means for practice
Although BoNT-A is not currently FDA approved for the treatment of IC/BPS, it is listed as fourth-line therapy for women with this condition. If initial therapies fail, it is appropriate to refer patients to a specialist, including a urogynecologist or urologist, where they may discuss BoNT-A therapy with or without hydrodistension.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545−1553.

The diagnosis of IC/BPS can be challenging due to a wide spectrum of symptoms, physical examination findings, and clinical test responses. The AUA developed its diagnostic and treatment guidelines mostly based on expert opinion, but they do provide a framework to help clinicians determine whether or not treatment for IC/BPS is warranted. The primary principles for evaluation are presented in FIGURE 1.

7,8

It is important to establish baseline voiding symptoms and pain levels with objective, validated instruments, including a voiding diary (FIGURE 2)⁹ and such patient questionnaires as the O’Leary Sant Interstitial Cystitis Index (ICSI; FIGURE 3).¹⁰ Characteristic IC/BPS voiding frequency is 10 or more times per day (to relieve pain, not to relieve a fear of wetting, which would be expected in a patient with overactive bladder).⁸ The ICSI questionnaire
should be used primarily to establish baseline symptoms, not as a diagnostic tool. A score higher than 8 has been used as inclusion criteria for therapeutic trials, however.¹¹

FIGURE 2 Voiding diary9

FIGURE 3 O’Leary Sant Interstitial Cystitis Index10

It is unnecessary to primarily perform cystoscopy or urodynamics, as there are no agreed-upon diagnostic criteria for these modalities for IC/BPS. They may be considered, however, if the patient does not respond to first- and second-line therapies. Additionally, potassium sensitivity testing is painful and, in view of the paucity of benefits, the risk/benefit ratio is too high to recommend for clinical care.

Treatment: Conservative first
The treatment for IC/BPS should start with more conservative therapy (including behavioral management and physical therapy). If symptom control is inadequate, other modalities should be employed. Behavioral modifications should include:

As noted in FIGURE 1, first make sure that patients do not have a urinary tract infection. If culture results are negative and other criteria fit, consider the diagnosis of IC/BPS and offer therapies as outlined in the ­treat‑
ment algorithm (FIGURE 4).⁷ Repeated 
treatment for negative results of urine cultures in patients with frequency, urgency, and bladder pain can lead to unnecessary antibiotics and delayed treatment of IC/BPS.

7

Treatments in FIGURE 4 are ordered from most to least conservative, and initial treatment depends on symptom severity, 
clinician judgment, and patient preference. If at any point in the patient’s care the diagnosis is questioned or treatments have been ineffective, referral to a specialist, including urogynecology or urology, may be appropriate.

Managing pain
Pain management is an important component at all levels of therapy, and pharmacologic pain management principles for 
IC/BPS should be similar to those for management of other chronic pain states. Options primarily include nonsteroidal anti-
inflammatory drugs (NSAIDs) and urinary analgesics (pyridium). The use of narcotics presents the risks of tolerance and dependence. If their use is necessary, all narcotic prescriptions must come from a single source and should be used as a component of multimodality therapy to minimize narcotic use.

Oral PPS is FDA approved for relief of bladder pain associated with IC/BPS

Nickel JC, Herschorn S, Whitmore KE, et al. Pentosan polysulfate sodium for treatment of interstitial cystitis/ 
bladder pain syndrome: insights from a randomized, double-blind, placebo-controlled study. J Urol. 2015;193(3):857−862.

In this multicenter, double-blind, randomized, placebo-controlled study, investigators evaluated the efficacy and tolerability of a decreased dose of PPS (100 mg daily) versus the current established dose (100 mg TID) in patients with IC/BPS.

Details of the study
A total of 368 participants (85.6% of whom were women) aged 18 to 78 years with 
questionnaire-diagnosed IC/BPS and no urinary tract infection for at least 6 months before screening were randomly assigned by a computer-generated randomization schedule in a 1:1:1 ratio to PPS 100 mg 3 times per day (FDA-approved dose), PPS 100 mg daily, or matching placebo. Safety assessments were performed at prespecified time points over 24 weeks. The primary efficacy endpoint was defined as a 30% reduction in ICSI total score. The study was powered to detect a 15% difference in the proportion of responders if there were 200 patients per treatment arm.

There was an interim analysis performed due to slow recruitment that led to early study termination, but all initially enrolled participants were included in the intention to treat analysis. Of the 368 patients, 162 (44%) withdrew from the study, with equal numbers in each arm. The treatment response rate was 40.7% for patients assigned to placebo, 39.8% for patients treated with PPS 100 mg once daily, and 42.6% for those treated with PPS 100 mg 3 times per day. These rates were not significantly different between groups.

Adverse events were equal between groups and included bladder pain, nausea,
headache, and exacerbation of IC/BPS 
symptoms. Gastrointestinal events led to the withdrawal of 10% of participants in the placebo group and 11% to 13% in the PPS 
groups. No clinically meaningful change was noted in laboratory tests, vital signs, or physical examination.

Study expands data on oral PPS
This was a multicenter, double-blind, randomized study of adults diagnosed with 
IC/BPS based on symptoms. Earlier studies of PPS efficacy, which provided the data for FDA approval of oral PPS, employed strict cystoscopic criteria for IC/BPS diagnosis.¹² Although the study was terminated early due to low recruitment and there was a high drop-out rate, there still was a large number of patients in each treatment arm. Furthermore, although the responder rate did not differ between groups, this may have 
been due to lack of power at the recruited numbers.

This study is an important glimpse into the use of oral PPS in a broad population of patients with bladder pain, urgency, frequency, and nocturia. It further emphasizes the need for improved diagnostic criteria to provide individualized, efficacious treatment for patients with IC/BPS.

What this EVIDENCE means for practice
Clinicians should continue to recommend conservative treatments for IC/BPS, including behavioral modifications, stress management, and manual physical therapy techniques prior to initiation of medications. Oral PPS may still be considered as a possible second-line therapy or as multimodal therapy for patients with IC/BPS.

Botulinum toxin-A with hydrodistention shows short-term efficacy as advanced therapy

In this multicenter, randomized, double-blind, placebo-controlled trial in patients with IC/BPS refractory to conventional treatment, investigators evaluated the efficacy and tolerability of hydrodistention plus suburothelial injections of onabotulinum toxin A (BoNT-A; Botox).

Details of the study
Sixty patients (86.7% female) aged 20 to 82 who had failed 6 months of conventional treatment for IC/BPS were enrolled. In this particular study, diagnosis was established based on symptoms and glomerulations on cystoscopy during hydrodistension. Patients were included if they had failed 2 prior treatment modalities for IC/BPS. Participants completed a baseline voiding diary, ICSI questionnaire, and visual analogue scale (VAS) for patient self-reported pain. All patients also received video-urodynamic testing prior to therapy.

Eligible patients were randomly assigned in a 2:1 ratio to either receive 100 units of intradetrusor BoNT-A or injection with normal saline immediately following cystoscopic hydrodistension under general anesthesia. All patients received oral antibiotics for 
7 days after therapy. Follow up was performed at 2, 4, and 8 weeks after treatment, with additional voiding diaries, symptom questionnaires, and VAS scores collected. At 8 weeks, a urodynamic study was performed.

The primary endpoint was reduction of pain on VAS score at the 8-week follow-up. With 60 participants, researchers had 85% power to detect a difference of 1.5 points on the VAS score between groups. Secondary outcomes included a composite global response assessment (GRA), ICSI scores, voiding diary parameters, and urodynamic findings.

No differences were noted in baseline measurements between the 2 groups except for VAS score, which was higher at baseline in the BoNT-A group (P = .056).

At 8 weeks, the BoNT-A group showed a significantly greater reduction than the saline group in the mean (SD) pain score (-2.6 [2.8] vs -0.9 [2.2], respectively; P = .021). Mean (SD) cystometric bladder capacity also increased significantly in the BoNT-A versus saline group (67.8 [164.3] vs -45.4 [138.5]; 
P = .020). Other secondary outcomes, including ICSI score, GRA, and functional bladder capacity as noted on voiding diary, improved significantly from baseline in both groups at 8 weeks.

Adverse events included dysuria, hematuria, urinary tract infection, and retention. There was a higher rate of dysuria noted in the BoNT-A compared with the saline group (40% vs 5%, respectively) at 8 weeks. There was only 1 urinary tract infection in each group, and only 1 patient had retention in the BoNT-A group, although study criteria for retention or need for self-catheterization was not provided.

Short-term efficacy, 
but more data needed
This was a well-designed trial evaluating the addition of BoNT-A to hydrodistension in a population of patients with refractory 
IC/BPS. The participants were mostly women and relevant to a gynecologic population. When utilized for patients with overactive bladder, 100 units of intradetrusor injections of BoNT-A has rates of urinary tract infection and retention of approximately 33% and 5%, respectively.¹³ Patients with IC/BPS undergoing this procedure should be counseled about these possible adverse effects. Furthermore, with a relatively short 8-week follow-up period, this study cannot be used to make any comments on long-term efficacy of this procedure.

What this EVIDENCE means for practice
Although BoNT-A is not currently FDA approved for the treatment of IC/BPS, it is listed as fourth-line therapy for women with this condition. If initial therapies fail, it is appropriate to refer patients to a specialist, including a urogynecologist or urologist, where they may discuss BoNT-A therapy with or without hydrodistension.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.