What is in the pipeline for new treatments for bladder pain syndrome/ interstitial cystitis?

PURPOSE OF REVIEW: Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years. RECENT FINDINGS: During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy. SUMMARY: Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.

Intratrigonal OnabotulinumtoxinA Improves Bladder Symptoms and Quality of Life in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Pilot, Single Center, Randomized, Double-Blind, Placebo Controlled Trial.

PURPOSE: We compared the efficacy and safety of trigonal injections of onabotulinumtoxinA and saline in patients with bladder pain syndrome/interstitial cystitis. MATERIALS AND METHODS: This phase II study enrolled women who had had bladder pain syndrome/interstitial cystitis for more than 6 months and pain for 4 months or longer on a visual analogue scale of 0 to 10, which were refractory to common treatment. OnabotulinumtoxinA 100 U in 10 or saline as placebo in 9 was administered as 10 trigonal injections of 1 ml. The primary study end point was the change from baseline pain intensity reported at week 12. Additional end points included O'Leary-Sant scores, micturition frequency, quality of life at week 4, 8 and 12, and the treatment benefit scale at week 12. Safety assessments included urinary tract infection, post-void residual urine and the initiation of clean intermittent catheterization. RESULTS: At week 12 onabotulinumtoxinA had significantly reduced pain compared with saline (mean ± SD -3.8 ± 2.5 vs -1.6 ± 2.1, p <0.05). The proportion of patients who achieved a 50% or greater reduction in the pain visual analog scale was 60% for onabotulinumtoxinA vs 22% for placebo. OnabotulinumtoxinA significantly improved O'Leary-Sant scores and quality of life over placebo at weeks 4, 8 and 12. Important numerical reductions in voiding frequency were also observed with the toxin. OnabotulinumtoxinA was well tolerated. Urinary tract infections developed in 3 patients who received onabotulinumtoxinA vs 2 who received saline. Mean post-void residual urine at week 12 was 5 ± 13 ml for onabotulinumtoxinA vs 0 ml with saline. This study had the limitations inherent to a single center trial with a small number of patients enrolled. CONCLUSIONS: OnabotulinumtoxinA 100 U caused significant and clinically relevant improvements in bladder pain and quality of life in patients with bladder pain syndrome/interstitial cystitis refractory to common therapy. It was also well tolerated.

The Role of Urinary VEGF in Observational Studies of BPS/IC Patients: A Systematic Review.

BACKGROUND: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition, often underdiagnosed, with an important impact on patient quality of life. More recently, an association between VEGF and its receptors has been suggested in BPS/IC pathophysiology, due to their role in promoting angiogenesis and inflammation, which can enhance bladder pain. Eventually, VEGF may be used as a biomarker for the diagnosis and prognostication of BPS/IC. To further clarify this issue, this review aims to critically summarize the available information, giving rise to a solid starting point for future studies. METHODS: We systematically searched PubMed and Embase, using the queries "urinary VEGF", "urinary VEGF" AND "pain", "urinary VEGF" AND "lower urinary tract symptoms" and "urinary VEGF" AND "LUTS" from January 2016 to February 2022. RESULTS: A total of 1026 papers were identified from which 7 articles were included in this study, which assessed 1036 participants. Regarding VEGF levels, overactive bladder (OAB) and healthy patients were used for comparison with BPS/IC patients. VEGF concentration seems to be higher when compared to healthy patients and overactive bladder (OAB) patients. Higher levels of VEGF were associated with pain severity, while a decrease in VEGF concentration was associated with pain and symptom improvement in women. However, these findings were not constant in all studies. CONCLUSIONS: There is a trend toward a relevant association between increased VEGF levels and pain or symptom severity in BPS/IC patients. Although there are some discrepancies among the studies and the number of patients included is small, VEGF and its receptors should be considered for future studies regarding its use in BPS/IC pathophysiology, diagnosis and prognostication.