For several years, the use of Botulinum Toxin A (BTA) for the treatment of refractory neurogenic detrusor overactivity (NDO) is recommended in second line therapy. The use of 200 U of Onabotulinum toxin A (OTA) is recommended after strong phase 3 studies. However, some patients can become refractory to the 200 U injections. For now, there is no recommendation for the management of BTA intradetrusor injections (IDI) failure. 
We aimed to evaluate the clinical and urodynamic efficiency of increasing Onabotulinum Toxin A (Botox®, Allergan, Inc) dose from 200 U to 300 U in case of failure of 200 U IDI in the treatment of NDO.

Patients who underwent a dose increase of OTA 200 to 300 U after failure of one or several OTA 200 U IDI, used once or for many years, at two departments of neurourology were retrospectively reviewed between July 2013 and January 2023. Only patients who performed exclusive self-intermittent catheterization with medullar disease (spinal cord injury, multiple sclerosis, myelitis, myelomeningocele) were included.
Primary outcome was clinical improvement of continence and urgency. Secondary outcomes were resolution of detrusor over activity in urodynamic and safety.

69 patients, 25 women and 44 men, aged 47.0 (±16.6) years were included. The mean time before a need to increase dose was 4.1 (±3.9) years for a median number of 5.2 (±5.6) injections of Botox® 200 U. There were 40 patients (58%) with spinal cord injury and 11 (16%) with multiple sclerosis. OTA IDI 300 U was efficient in 47 (68.1%) of patients who obtained a complete continence with improving urodynamic parameters. Decrease in number of urinary incontinence episodes per day was insufficient in 11 (15.9%). For 2 (2.9%) patients, efficacity was < 3 months, and for 9 (13%) there was a clinical improvement with an urodynamic control failure. There was no adverse event after increasing the dose. After a median follow up of 5.7 years, 40 patients (58%) were still treated successfully by OTA 300 U.

The only significant factor associated with first 300 U injection success was female status (96% of success in women, 77.3% in men; p=0.04). The only significant factor associated with first 300 U injection success was female status (96% of success in women, 77.3% in men; p=0.04) After a median follow up of 5.7 years, 40 patients (58%) were still treated successfully by OTA 300 U. The only significant parameter associated with persistence of use of 300 U injections was maximum cystometric capacity on urodynamics before the first injection (361.9 ml in persistence group and 236.5 ml in failure group; p=0.03). We observed more interruption of Botox® 300 U in patients with hypo compliance (44.5% vs 21.7%; p=0.12) as well as for patients in primary failure of Botox® 200 U (43.5% vs 25%; p=0.13) but this is not statistically significant.

Increasing Botox® dose from 200 to 300 U is an effective way of treatment after failure of 200 U in majority of patients with neurogenic detrusor overactivity. Further studies are needed to specify the indication of increasing dose therapy in BTA IDI failure, especially compared with switch to Abobotulinum toxin A.