Treatment choice, duration, and cost in patients with interstitial cystitis and painful bladder syndrome

This study has several important findings that shed light on the patterns of care for adults with IC/PBS. First, we found that all of the subjects were treated with at least one oral medication used to treat patients with IC/PBS during the study period. Of these, narcotics were the most commonly utilized class of medications. This might indicate that many commonly prescribed IC/PBS-specific medications are less effective than narcotics. Alternatively, the narcotics may have been used to treat other pain complaints arising from sites other than the bladder. Anticholinergics were the second most commonly utilized class of medications used by 49% of subjects (tolterodine and oxybutinin combined) with an average utilization period of approximately 1 year. This utilization period is actually longer than that documented for women with overactive bladder symptoms[10,11]. In the Interstitial Cystitis Data Base (ICDB) study, a multicenter, observational study designed to document the treatment history of IC/PBS and patient characteristics, only 2–4% of patients received anticholinergics as monotherapy or in combination with other medications [12]. However, this was a select cohort of patients who were recruited from a limited number of tertiary care centers. Our data suggest that anticholinergic agents are used much more widely in the community setting. This observation reinforces the inherent difficulty in distinguishing between the clinical syndromes of overactive bladder and IC/PBS, since many of symptoms overlap. It is possible that there is therapeutic benefit gained from this group of medications by patients with IC/PBS, or alternatively, they may have seen a slight benefit with little side effects and are willing to continue these medications since they were not offered other therapies.

A substantial minority of patients were treated with centrally acting medications including gabapentin and tricyclic antidepressants. These medications have been used in treatment of chronic pain conditions such as Complex Regional Pain Syndrome Type-I (CPRS-I) with success. It has been suggested that the pathophysiology of IC/PBS may partly be due to deregulation of the central nervous system, similar to CPRS-I [13]. Gabapentin, an antiepileptic, has been effective in treatment of chronic sympathetically mediated pain syndromes and there are reports of its efficacy in treatment of IC/PBS [13] [14]. Tricylic antidepressants such as amitriptyline also have demonstrated efficacy in treating patients with IC/PBS [15‐17]. In our cohort, gabapentin and amitriptyline were among the five most commonly used medications and were used to treat 19% and 25% of patients, respectively. This is slightly higher than the 17% of subjects treated with amitriptyline in the ICDB study [15‐17]. Given the theory that the etiology of IC/PBS/chronic pelvic pain may reside partly in the central nervous system, a shift toward treatments aimed at regulating the nervous system is logical. While claims data cannot be used to infer the reasons for the low rate of utilization of centrally acting medications in the Ingenix cohort, possible explanations include a lack of provider awareness of the potential role of central nervous system dysregulation in this syndrome or low perceived efficacy of available agents to mitigate this dysregulation. Further prospective work in this area would be helpful to further interpret this finding.

In our cohort, PPS was utilized by 35% of all subjects and 15% of the incident cases with a mean utilization period of 99.5 and 82 weeks, respectively. PPS is the only oral medication approved by the Food and Drug Administration (FDA) for the treatment of IC/PBS. One theory of the pathophysiology of IC/PBS implicates a defect in the bladder glycosaminoglycan layer as partially responsible for symptoms of IC/PBS. PPS, which is available in oral formulation and is excreted in urine, is prescribed with the intent to correct this defect [18]. The studies evaluating its efficacy have shown a wide array of clinical responses. A multicenter randomized controlled trial showed that 32% of those on PPS compared to 16% of patients on placebo reported more than 50% improvement in a global self-evaluation of their symptoms [18]. However, the Interstitial Cystitis Clinical Trials Group conducted a placebo-controlled trial to evaluate the efficacy of PPS and hydroxyzine, and found no statistically significant benefit to treatment with PPS.[19] In a systematic review of the pharmacologic management of IC/PBS by Dimitrakov et al., the pooled estimate of the effect of pentosan polysulfate therapy suggested a modest benefit, with a relative risk of 1.78 for patient-reported improvement in symptoms (95% confidence interval, 1.34–2.35)[20]. The long utilization period identified in our database also points to at least some therapeutic benefit enjoyed by the subjects. Alternatively, it may be a result of the manufacturer's recommendations that long-term therapy (greater than 1 year) may be needed before a clinical effect occurs.

We also found that more patients who were newly diagnosed with IC/PBS (31%) underwent hydrodistension, compared to those with a previous diagnosis (11%), and that the procedure was not repeated at a high rate. Hydrodistension has historically been used both for diagnosis and treatment of IC/PBS; however, after the NIH Interstitial Cystitis Database study documented that over 60% of patients regarded as having IC would have been excluded if the NIDDK criteria were applied[21], the diagnostic value of hydrodistension in clinical practice has been questioned[22]. The ICDB study similarly revealed that hydrodistension was utilized more frequently among those newly diagnosed (48.4%) compared to those with a previous diagnosis (25.7%)[16]. Our findings could partly reflect the use of this procedure as a diagnostic tool more frequently and less so as a therapeutic maneuver. It is also possible that when used for therapy, it was not repeated due to poor efficacy.

In our cohort, 26% of the patients had intravesical instillations; the average number of instillations ranged from two to six. A variety of Intravesical instillations have been used to treat IC/PBS, including silver nitrate, marcaine/lidocaine, dimethyl sulfoxide (DMSO), hyaluronic acid, heparin, PPS, Bacillus Calmette-Guerin (BCG), and rosiniferatoxin. DMSO is the only FDA approved intravesical agent for the treatment of this condition. The available Ingenix data do not allow us to identify the exact agent used for the instillations. These instillations are sometimes given as a 4–6 week course of therapy, while at other times they are given as ‘rescue’ therapy for symptom flares. These different uses may explain the variable numbers of instillations observed in our dataset.

A summation of all individual incremental care in patients with IC/PBS, exclusive of indirect costs, is estimated at $100 million in the US alone[5], and medical expenditures among IC/PBS patients are double the figure associated with those without the disease[23]. In our cohort, the overall expenditures related to the treatment of IC/PBS were $2,808 per subject over 5 years, the majority of which were related to oral medical therapy. PPS, the only FDA approved medication, was the most expensive at $36 per week. The weekly cost of $18 for oxybutynin and tolterodine is likely related to the use of the brand name or extended release formulations, which are more costly than short-acting formulas.

Although detailed clinical information cannot be obtained from claims-based data, claims data provides information about real-world practice patterns, including pharmacy care, in a large population of individuals. However, this study, like may claims-based analyses, has limitations. It is also important to note that this project is not designed to study the epidemiology of the disease, or to understand the rationale behind treatment, but rather studies a cohort of patients from 1 year treated by multiple providers. Claims-based data are designed for billing purposes, and therefore lack important information about severity of illness and reasons for treatment discontinuation. Coding is often incomplete or inaccurate, and our cohort may have included some patients with overactive bladder symptoms or other types of pelvic pain unrelated to IC/PBS. It is also possible that we excluded some subjects if their condition was coded using a combination of ICD-9 codes such as bladder pain and urgency/frequency, since we identified the cohort by the ICD-9 diagnosis for IC/PBS (595.1). Also, our cohort was older (mean age 63.3 years) than the reported mean age for patients with IC/PBS (age range 43–59 years) [2,19,24,25]. This could be partly due to the population under study; the population studied consists of the retirees, employees, and their dependants with a mean and median age of 58.5 and 59 years, respectively during the study year of 1999. Thus, our findings may not be entirely generalizable to a younger IC/PBS population.