Elmiron (pentosan polysulfate sodium) is currently the only FDA-approved oral medication for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS) in the United States. Other medications are used off-label, but none have received FDA approval due to their failure to demonstrate consistent statistical significance in studies. In the search to find alternatives for bladder pain management and bladder analgesic effects, one study attempted to look at the use of fulranumab, a human monoclonal antibody for nerve growth factor. Fulranumab has previously demonstrated clinical efficacy in the treatment of bladder pain in animal studies, as well as treatment of pain in humans with osteoarthritis and diabetic peripheral neuropathy. Initial studies involving the use of fulranumab in the treatment of IC/PBS showed promise, but subsequent studies have not been able to replicate those positive results. Unfortunately, this study was conducted during a period of time in which there was concern that anti-nerve growth antibodies like fulranumab could worsen osteoarthritis and osteonecrosis. Therefore, this study was ended early, and not enough subjects completed the study to determine a potential significance in the treatment of IC/PBS with fulranumab versus a placebo. Only ten patients received all three doses of fulranumab, while 15 patients received all three doses of the placebo. Patients demonstrated no statistically significant difference in pain control or analgesic effect. However, there was some perceived improvement on the global assessment scale among the group treated with fulranumab, indicating overall improvement. Patients in the fulranumab group also reported less disease duration and lower daytime frequency. Common side effects were diarrhea, carpal tunnel syndrome, and urinary tract infections, which were determined to be either not related or doubtfully related to the use of fulranumab. The study continued to follow patients for 26 months following the last dose.

In 2015, the FDA allowed for the further development and study of anti-nerve growth antibodies to resume. Anti-nerve growth antibodies are currently being studied in the treatment of osteoarthritis and low back pain. Further studies are needed to determine the safety and potential effectiveness of these drugs for the treatment of IC/PBS.

—By Christina Hicks
Christina Hicks, MS, APRN, WHNP-BC, is a women’s health nurse practitioner in urogynecology with a special interest in interstitial cystitis, chronic pelvic pain, and women’s sexual health. She lives in Dallas, Texas.

While dimethyl sulphoxide (DMSO) remains the only bladder instillation medication approved by the U.S. Food and Drug Administration for interstitial cystitis/painful bladder syndrome (IC/PBS), chondroitin sulphate bladder instillations have been approved in both Canada and Europe for use in the treatment of IC/PBS. Both medications seem to have an important role in the repair of the glycosaminoglycan (GAG) layer of the bladder, which is often damaged or deteriorated in IC patients. Previous studies have shown patient improvement with the use of chondroitin sulphate bladder instillations, but no study has been able to demonstrate statistical significance to support its use. This most recent trial aimed to compare the use of DMSO vs. chondroitin sulphate for bladder instillation treatment, but it was discontinued before completion due to a high withdrawal rate from the study as a result of intolerable side effects from DMSO. The most common side effects were pain and dysuria, and a less common but bothersome side effect was a strong garlicky body odor for up to seven hours post-instillation. Before the trial was discontinued, however, patients receiving chondroitin sulphate 2% showed improvement in pain reduction and nighttime frequency of urination. The use of chondroitin sulphate 2% also demonstrated minimal side effects. This trial demonstrates potential for the use of chrondroitin sulphate in bladder instillations, but further research, especially in comparison to other bladder instillation options, is needed.

—By Christina Hicks
Christina Hicks, MS, APRN, WHNP-BC, is a women’s health nurse practitioner in urogynecology with a special interest in interstitial cystitis, chronic pelvic pain, and women’s sexual health. She lives in Dallas, Texas.

This case report concerns a 35-year-old woman with interstitial cystitis (IC) who received a non-invasive treatment known as pulsed radiofrequency (PRF), in which a needle is used to deliver short bursts of energy to nerve tissue. In particular, the treatment was applied to the patient’s superior hypogastric plexus, a network of nerves in the abdomen. Over the preceding 7 years, the patient experienced pain in the lower abdomen due to bladder filling, pain near the vulva during sleep or changing posture, and other symptoms including urinary urgency and frequency, and nocturia. She had tried a variety of standard treatments, and none were very effective against pain and symptoms; these included bladder hydrodistension, sodium chondroitin sulfate given intravesically, and oral medications such as pentosan polysulfate and gabapentin. Given this situation, the authors decided they would try blocking the superior hypogastric plexus using anesthetic, which successfully but temporarily improved the patient’s pain. Because of these encouraging results, the patient underwent a session of PRF treatment of the superior hypogastric plexus, plus a second session 6 months later. The treatment seemed to be successful, and relieved pain and symptoms for at least 2 years and 6 months, according to this case report. Based on this experience, the authors say that PRF treatment could provide long-term improvements in pain and symptoms for other IC patients who aren’t achieving relief with standard treatments. However, it’s important to note that this treatment remains experimental, and would need to be more carefully studie to confirm it’s both safe and effective in this setting.

In this randomized study, women with interstitial cystitis/bladder pain syndrome (IC/BPS) received either chondroïtin sulphate or dimethyl sulphoxide (DMSO). Both treatments were administered intravesically (ie, directly to the bladder via a catheter) weekly for a total of 6 weeks. However, of the 14 patients who started DMSO, only 6 completed the study; reasons they gave for dropping out included pain (during or after treatment administration), lack of efficacy, and the “intolerable” garlicky odor of DMSO. This high drop-out rate led the investigators to recommend that DMSO be “used with caution” and with active monitoring for adverse reactions. By contrast, the 22 patients in the chondroitin sulfate group reported moderate or marked improvement of IC/BPS much more often (73%, vs 14% for the DMSO group). In particular, the chondroitin sulfate-treated women more often reported reductions in pain, nighttime urination, and other measures. Ultimately, this trial was halted due to the high number of dropouts in the DMSO group, so more study will be needed to determine the relative benefit of these intravesical treatments for IC/BPS. However, this study does provide at least some additional evidence that chondroitin sulfate is likely a superior treatment choice of treatment when compared with DMSO. In September, Cervigni and colleagues reported a larger study of chondroitin sulfate versus DMSO (110 patients) in which women who received chondroitin sulfate given according to the planned treatment protocol had greater reductions in pain intensity, and fewer side effects, compared with women who received DMSO.

Previous studies have shown that hyaluronic acid (HA) plus chondroitin sulfate (CS) is a potentially promising treatment for women with interstitial cystitis/bladder pain syndrome (IC/BPS). It this study, investigators compared HA/CS to dimethyl sulfoxide (DMSO) in 110 women with IC/BPS. About two-thirds of the women received HA/CS, and the rest received DMSO. Both treatments were delivered directly to the bladder using a catheter for a total of 13 weeks, or approximately 3 months. Patients were evaluated at 6 months after the treatment start date. Investigators found that both HA/CS and DMSO treatment resulted in significant reductions in pain intensity. However, when the analysis was limited to those women who received treatment exactly as planned, they found the reduction in pain intensity was greater for those receiving HA/CS. Moreover, less than 2% of patients had adverse effects related to HA/CS, compared with 22% in the DMSO group. Finally, while both treatments improved quality of life, HA/CS had a more favorable cost-effectiveness profile, meaning that the treatment is a better value for each health care dollar spent, at least in this study.

Patients who have had back surgery in the past sometimes present with lower urinary tract problems. There is some concern that the prior back surgery could be problematic in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who are selected to undergo neuromodulation, a treatment which involves the application of electrical current directly to nerves. Accordingly, this group of investigators carefully reviewed and evaluated 560 patients, of whom 109 (19%) had had back surgery; those patients tended to be older and were more likely to have urge urinary incontinence. However, implantation of a neuromodulation device was no less successful in this group of patients, and they had similar levels of interstitial cystitis symptoms and quality of life as compared with patients who had no prior back surgery. The back surgery patients were more likely to report incontinence before the treatment, but after the treatment, this parameter improved. The one difference investigators did find was that back surgery patients did not have a significant improvement in volume per void; however, most patients reported moderate/marked improvement in bladder symptoms overall. Based on that, investigators said their study showed that neuromodulation is a reasonable treatment option for IC/BPS patients whether or not a patient has undergone back surgery in the past.

In this study, investigators studied a surgical technique called transurethral resection (TUR) in patients with ulcerative interstitial cystitis (IC). They wanted to see if the efficacy of the procedure could be improved when it’s combined with hydrodistention, a therapeutic technique that, like it sounds, involves filling the bladder with water. The study included 44 women with recently diagnosed IC, 22 of whom received TUR alone, and 22 who underwent TUR plus hydrodistention. Both groups had marked reductions in pain, and the improvement was the same, suggesting no difference between the two strategies. However, TUR combined with hydrodistention did improve bladder capacity, and also improved voiding symptoms, suggesting the combination offers benefits over and above TUR alone for women who have ulcerative interstitial cystitis.

Numerous studies suggest botulinum toxin A may be effective in controlling symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS); however, many of those studies are not rigorous (e.g., they don’t include a control group for comparative purposes). More recently, higher quality, controlled studies have been published, prompting this research group to conduct a meta-analysis (a study of studies) to evaluate high-level evidence on the efficacy and safety of this treatment. They looked at a total of 7 randomized, controlled trials and one retrospective study. Taken together, the results suggested patients receiving botulinum toxin had a greater reduction in pelvic pain, a significant improvement in urination frequency during the day, and significant improvements in IC/BPS symptoms overall. The trade-off might be a slightly larger volume of post-void residual urine in the treatment group, and no improvements were noted in urinary tract infections, nocturia, dysuria, and urinary flow rate. Taken together, these findings suggest that botulinum toxin injections might be a promising treatment option to improve bladder pain and other aspects of IC/BPS. However, the researchers did emphasize that larger well-designed trials would be needed to confirm these findings.

Intravesical instillation is a treatment strategy where a specific agent is delivered directly to the bladder using a catheter. There are several different intravesical treatments available for interstitial cystitis/bladder pain syndrome (IC/BPS); these include botulinum toxin A, bacillus Calmette-Guerin (BCG), lidocaine, chondroitin sulfate, and pentosan polysulfate, among others. There are various studies suggesting that all of these treatments can provide some relief of symptoms. However, it’s still unclear whether any of these therapies is better than the others when delivered intravesically. Accordingly, these researchers conducted a meta-analysis of 16 clinical trials representing 905 patients. In particular, they sought to compare Global Response Assessment (GRA), a measure used as an endpoint in many IC/BPS trials today. Botulinum toxin and BCG both provided significant improvement in GRA, but it was botulinum toxin that had the greatest probability of being the best treatment course, according to the investigators. Botulinum toxin also significantly improved bladder capacity. Of note, the analysis also revealed that pentosan polysulfate significantly improved both urinary frequency and urgency symptoms. While the findings do suggest some intravesical treatments are superior to others, further studies (particularly ones comparing the treatments head-to-head) would provide better insights into the relative efficacy of intravesical treatments for IC/BPS.

In this systematic review and meta-analysis of previously published studies, investigators sought to determine the potential benefits of hyaluronic acid (HA), alone or in combination with chondroitin sulfate (CS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These treatments are delivered intravesically, or directly to the bladder via a catheter. While such treatments are already recommended in recent treatment guidelines, there is a need to better characterize the effects of treatment and determine the potential benefit for patients. In their review, the authors included a total of 10 published studies including a total of 390 patients. They found that the HA treatments significantly improved patient-rated pain and symptoms of IC/BPS. The main endpoint they looked at was pain symptoms as measured by a visual analogue scale (VAS), and they found the beneficial effect on VAS was consistent across 9 studies. Based on these findings, the authors believe that intravesical instillation of HA or HA/CS could be considered as a potential treatment for patients with IC/BPS.