Effectiveness and Safety of Intradetrusor OnabotulinumtoxinA Injection for Neurogenic Detrusor Overactivity and Overactive Bladder Patients in Taiwan—A Phase IV Prospective, Interventional, Multiple-Center Study (Restore Study)

We conducted a phase IV, pre/post multi-center study to evaluate the efficacy and safety of intradetrusor onabotulinumtoxinA injection in patients with neurogenic detrusor overactivity (NDO, n = 119) or overactive bladder (OAB, n = 215). Patients received either 200U (i.e., NDO) and 100U (i.e., OAB) of onabotulinumtoxinA injection into the bladder, respectively. The primary endpoint for all patients was the change in the PPBC questionnaire score at week 4 and week 12 post-treatment compared with baseline. The secondary endpoints were the changes in subjective measures (i.e., questionnaires: NBSS for patients with NDO and OABSS for those with OAB) at week 4 and week 12 post-treatment compared with baseline. Adverse events included symptomatic UTI, de novo AUR, gross hematuria and PVR > 350mL were recorded. The results showed that compared with baseline, PPBC (3.4 versus 2.4 and 2.1, p < 0.001) and NBSS (35.4 versus 20.4 and 18.1, p < 0.001) were significantly improved at 4 weeks and 12 weeks in NDO patients. In addition, compared with baseline, PPBC (3.5 versus 2.3 and 2.0, p < 0.001) and OABSS (9.1 versus 6.2 and 5.7, p < 0.001) were significantly improved at 4 weeks and 12 weeks in OAB patients. Eight (6.7%) had symptomatic UTI and 5 (4.2%) had de novo AUR in NDO patients. Twenty (9.3%) had symptomatic UTI but no de novo AUR in OAB patients. In conclusion, we found that intradetrusor onabotulinumtoxinA injections were safe and improved subjective measures related to NDO or OAB in our cohort.

Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

Background Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway. Methods Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Acetylcholine and adenosine triphosphate content in the voided cystometry fluid were determined. Expressions of M2, M3 and P2X3 receptor in the bladder mucosa were evaluated. Results Moxibustion treatment prevented the development of detrusor overactivity in SCI rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2, but not M3, was markedly suppressed by moxibustion, accompanied by a reduction in the level of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion. Conclusions Moxibustion is a potential candidate for treatment of neurogenic bladder overactivity in a rat model of spinal cord injury possibly through inhibiting the M2/ATP/P2X3 pathway.