*Limitations*

The main limitations of the study are the relatively small number of patients recruited, which were limited by the off-label nature of this treatment and the retrospective analysis of clinical records, and with the inherent risk of bias associated with the quality of the information in the files, including missing data. In addition, we could not provide reliable data on day and night time voiding frequency that we observed to decrease significantly in other studies [5]. However, from our perspective, it can be a more accurate representation of this treatment in real-world clinical practice. In this real-life scenario, the therapeutic effect of each treatment was determined by the time until a treatment request was made by the patients to avoid the bias of treatment delays due to fluctuations in the waiting list.

The readers should also be aware that different from evaluating oral pharmacological treatment effects, the OnaBotA treatment is a surgical procedure and there could be intersurgeon variations of the surgical technique. We believe that this bias has a low impact as the procedure is well standardized.

Another limitation of this real-life study is relative to the use of other drugs other than OnaBotA by patients in this cohort. While patients could be medicated with a small number of pain-killers during the injections performed in a trial setting, these trial setting injections just represent a minor number of the treatments in the cohort. All of the other patients treated outside of a trial setting, and even trial patients once off the trial, were able to be medicated, or even automedicated, with non-opioid analgesics, anti-depressants and anti-histaminics to better control the symptomatology at their own discretion. Additional medication would probably be taken more often when the OnaBotA's effect begun to decrease. However, this is a real-life setting, and BPS/IC patients rarely achieve symptom control with monotherapy (especially the patients represented in this cohort that are refractory to oral and intravesical treatments). Despite the fact that other medical therapies could have a role in explaining a more prolonged time of symptoms being under control and, consequently, a greater interval between OnaBotA injections, what is most important is that the BPS/IC condition was better controlled after OnaBotA treatments in responders.

The fact that this study reflects a real-life scenario could sugges<sup>t</sup> that the mild adverse effects, being easily treated, could be underreported.
