|Year : 2021 | Volume
| Issue : 1 | Page : 3-8
Effectiveness of oral pentosan polysulfate in painful bladder syndrome: Is it worth the cost?
Devdatt Purushottam Palnitkar1, Prakash Patankar2, Suresh Patankar3
1 Palnitkar Hospital, Maharashtra University of Health Sciences, Bhagyanagar, Aurangabad, Maharashtra, India
2 Patankar Nursing Home, Chiplun, Maharashtra, India
3 ACE Hospital and Research Centre, Erandwana, Pune, Maharashtra, India
|Date of Submission||16-Aug-2020|
|Date of Decision||15-Jan-2021|
|Date of Acceptance||15-Jan-2021|
|Date of Web Publication||16-Mar-2021|
Dr. Devdatt Purushottam Palnitkar
Palnitkar Hospital, Maharashtra University of Health Sciences, Bhagyanagar, Aurangabad 431001, Maharashtra.
Source of Support: None, Conflict of Interest: None
Introduction: Oral pentosan polysulfate (PPS) is a recommended treatment in painful bladder syndrome (PBS); efficacy and cost-effectiveness of PPS have not been compared against the treatment with anticholinergics. Aim: This pilot study compared the effectiveness of oral PPS and anticholinergics and the cost of treatment for both. Materials and Methods: Thirty consecutive female patients presenting in Urology outpatient clinics were included in the study after obtaining clearance from the research and ethics committee. Twelve patients in each arm A and B completed the course of treatment and follow-up. Patients in each group were comparable symptomatically and epidemiologically. The patients in group A received oral PPS 100 mg three times daily for 3 months, whereas the patients in group B received anticholinergic drugs (oxybutynin chloride 2.5 mg twice daily) for 3 months. Efficacy based on symptom score and quality of life (QoL) scores along with cost-effectiveness was compared between the two groups. Results: In relief of symptoms and improvement in the QoL, there was no statistical difference in the findings of the two groups. The cost of therapy for the two groups was significantly different (P = 0.09). The cost of treatment with PPS was higher by two to three times the cost of treatment in the other groups. Conclusion: PPS does not offer any therapeutic advantage over oxybutynin chloride and is a costlier form of treatment.
Keywords: Oxybutynin chloride, painful bladder syndrome, pentosan polysulfate, quality of life
|How to cite this article:|
Palnitkar DP, Patankar P, Patankar S. Effectiveness of oral pentosan polysulfate in painful bladder syndrome: Is it worth the cost?. MGM J Med Sci 2021;8:3-8
|How to cite this URL:|
Palnitkar DP, Patankar P, Patankar S. Effectiveness of oral pentosan polysulfate in painful bladder syndrome: Is it worth the cost?. MGM J Med Sci [serial online] 2021 [cited 2021 Apr 14];8:3-8. Available from: http://www.mgmjms.com/text.asp?2021/8/1/3/311383
| Introduction|| |
Painful bladder syndrome (PBS) is a chronic painful disease characterized by symptoms such as pain sensation in the bladder, pressure sensation, frequency of urination, and urgency. In the absence of a complete understanding of the etiology and pathophysiology of the disorder, the diagnosis is based on clinical findings. PBS severely affects the quality of life (QoL) in the form of decreased work outcomes, social and emotional changes, sleep, and sexual satisfaction. A study reported that patients with PBS had lower physical functioning, lower mental health, and sexual health in comparison to healthy controls. Symptoms of the disease may overlap with other diseases, such as the overactive bladder (OAB), vulvodynia, and endometriosis. Patients are initially managed using behavioral therapy. However, patients often require pharmacological treatment in the form of oral or intravesical drugs. Oral pentosan polysulfate (PPS) sodium or intravesical dimethyl sulfoxide (DMSO) is recommended for the treatment of PBS in the United States.
PPS is a mucopolysaccharide and is thought to provide a protective barrier to the injured wall of the urinary bladder. Oral PPS was initially used in 1987 in the patients with PBS, and it was reported that 4-month treatment of oral pentosan had no significant beneficiary effect in the patients with PBS. A recent meta-analysis of six randomized controlled trials revealed that oral PPS is effective in reducing pain and urinary urgency. Oral treatment for long term with PPS is associated with adverse effects such as diarrhea and vomiting. Intravesical PPS administration for 6 weeks was found to be effective in the treatment of PBS.
PPS has been compared with placebo in several studies. Efficacy and safety and cost-effectiveness of PPS have not been compared with anticholinergics (also a second-line therapy) in patients with PBS.
| Materials and methods|| |
The study was carried out as a pilot study and as a prelude to a larger study that involves a comparison of oral PPS with intravesical liposome treatment. This pilot study was carried out at three urology care centers. All the three centers followed standard selection, treatment, and follow-up protocol. The first 30 patients (age 25–70 years) reporting at the three centers, diagnosed to have PBS based on the National Institute of Diabetes and Digestive and Kidney diseases (NIDDK) criteria, and consenting to participate in the study, were included. Pregnant women or likely to be pregnant women and patients with active culture-proven urinary bacterial infection or other illness like stones were excluded.
Based on a prevalence of 3% as reported in the literature, the number of patients to be included in the pilot study was calculated to be 12 in each group. Selected patients were allocated alternately to one of the groups: group A—treatment with oral PPS, along with analgesics and anti-inflammatory drugs as required and group B—treatment with anticholinergics, along with analgesics, anti-inflammatory drugs as required. Alternate patients were allocated to each of the two groups A and B, without blinding. Twenty-four patients (12 from each group) completed the treatment protocol and follow-up and were included in the final analysis.
The inclusion criteria were: female patients presenting with symptoms during the study, diagnosed with PBS, age between 25 and 70, and consent to enter the study. The exclusion criteria were pregnant women, compensated renal function, known drug allergies, and patients failing to continue treatment and follow-up. The patients in group A received oral PPS 100 mg three times daily for 3 months, whereas those in group B received anticholinergic (oxybutynin chloride 2.5 mg twice daily) for 3 months. Both the groups received analgesics and anti-inflammatory agents as required. In patients with acute symptoms, analgesic/anti-inflammatory treatment was given in the form of oral Tab. Aceclofenac 50 mg in combination with Tab. Paracetamol 500 mg twice daily after food. This treatment was never given for longer than 5 days in any patient. Tab. Rabeprazole 20 mg once daily was given along with the combination of Tab. Aceclofenac/Paracetamol. In both the groups, three patients each required treatment with a combination of Aceclofenac+Paracetamol/Rabeprazole in the first week of treatment for 3–5 days. This was not repeated later.
Patients were evaluated with a peer-evaluated questionnaire-based symptom score that is based on the O’Leary Sant symptom questionnaire and QoL score at the beginning of the study and 1 and 3 months after starting treatment. Both the questionnaires were peer-evaluated for efficacy in capturing symptoms and the QoL of patients. The questionnaires were assessed for ease of use on a few patients before adopting them.
The efficacy of treatment was evaluated using a symptom score questionnaire. The questionnaire is based on the O’Leary Sant symptom questionnaire, modified to suit language and cultural requirements. A maximum score of 14 and a minimum score of 0 is possible on the questionnaire. The patients were assessed at the beginning of the study for baseline score and then at 1 and 3 months after starting treatment.
The improvement in symptom score was graded as (1) score same as in the beginning or worse (no relief), (2) scores <75% but >50% of original (mild relief), (3) scores <50% but >25% of original (moderate relief), (4) scores <25% of original (major relief), and (5) score 0 (cure).
Quality of life
QoL was measured using a QoL questionnaire. The questionnaire was based on the QoL issues faced by patients with PBS. The questionnaire was peer-reviewed for efficacy in capturing accurately and adequately the QoL of a PBS patient. The change in the QoL of a patient was gaged as (1) score same as at the beginning or worse (no relief), (2) scores <75% but >50% of original (mild relief), (3) scores <50% but >25% of original (moderate relief), (4) scores <25% of original (major relief), and (5) score 0 (cure).
Data were presented as frequency, percentage, median, and interquartile range (IQR). The normality of data was calculated using the Shapiro–Wilk test. Quantitative variables between the groups were compared using the Mann–Whitney U-test. Categorical variables were compared using Fisher’s exact test. P-value <0.05 was considered significant. Statistical analyses were performed using SPSS v21.0.
| Results|| |
Thirty patients with PBS included in this study were allocated to group A and group B alternately to receive either PPS (group A) or anticholinergics (group B). Of the 30 patients included in the study, 24 patients (12 in each group A and B) completed the treatment prescribed and follow-up and were included in the final analysis [Table 1]. In this study, the median age of the patients in group A was comparable to the mean age of the patients in group B (40.0 (34.5, 58.5) vs. 45.0 (34.0, 50.5); P = 0.917) [Figure 1]A. All of the patients in both groups were females. The median duration of symptoms in group A was significantly higher than that in group B (36.0 (21.0, 43.0) vs. 18.0 (12.0, 25.0); P = 0.036) [Figure 1]B.
In the study, symptom score was comparable to pre-treatment. At 1 month and 3 months, there was no statistically significant difference in symptom score between both the groups (P > 0.05) [Table 2]. We also observed that at 1 month in group A, one patient showed resolution of symptoms whereas two patients in group B showed resolution. The resolution was defined as a 50% decrease in the symptoms when compared with baseline. However, 80% of the patients in group A had mild relief, whereas 60% of the patients in group B had mild relief. At 3 months, 80% of the patients in group A and 40% of the patients in group B showed resolution of symptoms (P = 0.894).
|Table 2: Comparison of symptom score between both the groups at different times |
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Quality of life
In our study, the QoL score was comparable to pre-treatment. At 1 month and 3 months, there was no statistically significant difference in QoL score between both the groups (P > 0.05) [Table 3]. We also observed that at 1 month, 80% of the patients in group A had mild relief, whereas all patients in group B had mild relief. At 3 months, all the patients in group A and group B had mild relief in the QoL score.
|Table 3: Comparison of QoL score between both the groups at different times|
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Our study observed that the median cost of PPS was significantly higher than anticholinergics (5850 (5650, 6300) vs. 1200 (1050, 1300); P = 0.009) [Figure 1C]. Adverse effects were not studied as a part of this study. No patient had allergic reactions or GI, renal, or neurological symptoms attributable to the drugs used during the period of the study. The patients who did not complete treatment or follow-up did not assign any specific cause for not completing.
| Discussion|| |
In a pilot study of 24 patients with PBS, PPS was not found to be more effective against anticholinergics in terms of efficacy based on symptom score and QoL score. However, both treatments were efficacious as well as showed improved QoL.
Patients of PBS may have obstructive symptoms at times. This can lead to confusion in diagnosis, especially in men. Stricture urethra and prostatomegaly may be wrongly thought to be the cause of symptoms in such cases. In an Indian study, it was found that 38% of the patients had some obstructive symptoms. The presence of anal discomfort, vulvar and glandular pruritis and burning, dyspareunia, painful ejaculation, and difficulty in walking and sitting were seen in up to 25% of the patients in this study. We did not evaluate our patients for these associated symptoms.
Nickel et al. used interstitial cystitis symptom index to study the effect of PPS and reported that there was no treatment effect and there were 10.2–13.3% of patients who discontinued treatment due to adverse events. In our study, although PPS was found to be efficacious, it was not significantly more efficacious than anticholinergic drugs.
Most of the studies have used patient-reported self-outcome measures for evaluation of the efficacy of PPS. Our study also uses a symptom and QoL score for the assessment of efficacy. This can lead to bias. A larger study may be required to ascertain the findings of this pilot study and to reduce bias. Although many of the studies have reported no beneficial effects of PPS, oral PPS continues to be the recommended treatment for PBS as seen in the American Urology Association guidelines. Variations in the wording of a question can lead to different responses and different conclusions. In our study, we based our questionnaire on the O’Leary Sant questionnaire, dividing it for evaluation of results between a symptom score and a QoL score. We translated the questionnaire into the local language. This questionnaire was circulated among 12 peer urologists to assess effectiveness in capturing accurately desired data. Responses of peers were studied and were used to modify the questionnaire suitably. The modified questionnaire was then used on non-ICPBS and ICPBS patients in the OPD to assess ease of understanding and effectiveness in the assessment. Any new questionnaire has to go through this process before validating it for use in a trial.
Most studies have compared PPS with placebo. In our study, efficacy was evaluated against anticholinergics. Anticholinergic drugs such as oxybutynin and tolterodine are effective in placebo-controlled trials in cases of OAB; these drugs have a few adverse effects including dry mouth. A meta-analysis showed an improvement in QoL in patients with anticholinergic drugs in OAB, although their long-term benefit is unknown. In addition to this, Madhuvrata et al. recently in an intervention review found that anticholinergic drugs have significantly better QoL and efficacy in comparison to placebo in OAB; however, the treatment results in discontinuation of therapy due to adverse events. PBS and OAB share many common and overlapping symptoms. The only differentiating symptom is pain in the pelvic region in cases of PBS. It is not surprising, therefore, that patients of PBS, as seen in our study, had significant relief with an anticholinergic drug.
In a meta-analysis of the effectiveness of anticholinergic drugs in OAB, the findings were that at the end of the treatment period, cure or improvement (relative risk (RR) 1.39, 95% confidence interval (CI) 1.28–1.51), the difference in leakage episodes in 24 h (weighted mean difference (WMD) ‒0.54; 95% CI ‒0.67 to ‒0.41), and the difference in the number of voids in 24 h (WMD ‒0.69; 95% CI ‒0.84 to ‒0.54) were statistically significant favoring medication. Statistically significant but modest-sized improvements in QoL scores were reported in recently completed trials. There was three times the rate of dry mouth in the medication group (RR 3.00, 95% CI 2.70–3.34) but no statistically significant difference in withdrawal (RR 1.11, 95% CI 0.91–1.36). Sensitivity analysis, while limited by small numbers of trials, showed little likelihood that the effects were modified by age, sex, diagnosis, or choice of drug.
Treatment in addition to being efficacious should also be cost-effective for long-term compliance. In developing countries like India, cost-effectiveness remains a very important consideration while choosing the best effective treatment. In our study, PPS treatment was associated with significantly higher costs in comparison to anticholinergics. Previously, it was suggested that PPS is not cost-effective when compared with best-supported therapies. Our study also concluded that treatment with PPS is efficacious but costlier than other equally efficacious treatments.
| Conclusion|| |
PPS may not be the best possible option in the treatment of patients of PBS as a cheaper and equally effective treatment option with anticholinergics is available.
Ethics Committee approval
Institutional Ethics Committee, ACE Hospital, and Research Center Pune (Reg. No. ECR/474/Inst/MH/2013, dated: 14/10/2013). Ref. no. AMAI/Ace-01/Ph.D/2017.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]