Clinical Review
Chronic vulvar symptoms and dermatologic disruptions: How to make the correct diagnosis
When a patient reports chronic symptoms, it’s important to look beyond yeast infection and other common causes to accurately identify her...
Cindy L. Amundsen, MD, and Megan Bradley, MD
Dr. Amundsen is Roy T. Parker Professor of Obstetrics and Gynecology, Division of Urogynecology and Reconstructive Pelvic Surgery, and Associate Professor of Surgery, Division of Urology, at Duke University Medical Center, Durham, North Carolina.
Dr. Bradley is Fellow, Obstetrics and Gynecology, Division of Urogynecology and Reconstructive Pelvic Surgery, at Duke University Medical Center.
The authors report no financial relationships relevant to this article.
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.
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