*Article* **Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome**

**Wan-Ru Yu 1,2,3, Yuan-Hong Jiang 3, Jia-Fong Jhang 3, Wei-Chuan Chang 4 and Hann-Chorng Kuo 3,\***


**Abstract:** Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome.

**Keywords:** interstitial cystitis/bladder pain syndrome; botulinum toxin A injection; urine biomarkers; bladder inflammation

**Key Contribution:** Botulinum toxin A injections for interstitial cystitis/Bladder Pain Syndrome (IC/BPS) is effective in 40% of the patients studied. Patients with lesser bladder inflammation as characterized by a larger maximal bladder capacity on hydrodistention, lower urinary biomarker MCP-1 and oxidative stress biomarker 8-isoprostane levels, and fewer IC symptoms might achieve satisfactory treatment outcomes.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a urinary bladder disorder characterized by chronic pelvic pain, pressure, or discomfort, and is accompanied by urinary symptoms, including urinary frequency, nocturia, and urgency [1]. Its prevalence was reported to be 0.04% and 0.26% in Taiwan and Korea, respectively [1]. In other words, there are approximately 100,000 people with IC/BPS in Taiwan. The pathophysiology is still unclear, and patients with this condition have not achieved satisfactory treatment

**Citation:** Yu, W.-R.; Jiang, Y.-H.; Jhang, J.-F.; Chang, W.-C.; Kuo, H.-C. Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome. *Toxins* **2022**, *14*, 871. https://doi.org/ 10.3390/toxins14120871

Received: 4 November 2022 Accepted: 9 December 2022 Published: 11 December 2022

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outcomes [2]. IC/BPS can be classified into Hunner's (HIC) or non-Hunner's (NHIC) ulcer types [1]. The most common pathological findings are urothelial denudation and bladder inflammation [2]. Failure to achieve full urothelial regeneration results in potential breaches in barrier function that may increase an individual's susceptibility to infection or increase sensory fiber stimulation [3]. Nevertheless, multimodal therapies may be necessary to improve not only the physiological but also the psychological well-being of patients [4].

Previously, the American Urology Association (AUA) guidelines for IC/BPS recommended six steps of treatment; however, recently most guidelines do not recommend stepby-step treatments. Instead, multiple and simultaneous treatments were suggested [1,4–6]. Overall, the treatments include pain control, lifestyle modification, stress management, pelvic floor muscle therapy, oral therapies, intravesical therapies, and novel treatment for bladder inflammation [2].

As anti-inflammation and pain control is important for IC/BPS patients, the focus on bladder urothelium treatment is indispensable [7]. Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through its anti-inflammatory and antinociceptive effects in the bladder urothelium [8]. BoNT-A not only reduces bladder pain effectively but it also increases bladder capacity in patients with cases of IC/BPS that are refractory to conventional therapy [9,10]. Furthermore, BoNT-A is capable of gradually decreasing bladder inflammation and enhancing urothelial repair, leading to symptomatic relief [11,12].

Due to IC/BPS's refractory nature, further research and investigation is vitally important. In real-world practice, precision medicine can not only assist clinical doctors in identifying suitable treatment options but could also help IC/BPS patients achieve satisfactory treatment outcomes earlier. Recently, the correlations between urinary biomarkers and the pathophysiology of IC/BPS were explored [13]. However, the self-reported outcomes, according to the IC/BPS patients' point of view, have not been investigated. Moreover, data relating to the effects of intravesical BoNT-A injections on improved self-reported treatment outcomes, and the predictive value of urinary biomarkers among IC/BPS patients are still lacking. Therefore, we aimed to investigate the treatment outcomes of intravesical BoNT-A injections in patients with IC/BPS in a real-life setting.
