Recent published studies on the long-term efficacy and safety of Onabotulinumtoxin A (Onabot/A) in both idiopathic and neurogenic detrusor overactivity (IDO, NDO), reported a large intra-individual variability or a loss of response along repeat treatments, with high rates of urinary tract infections (UTIs) and bacteriuria after the intravesical administration of the neurotoxin. IncobotulinumtoxinA (Incobot/A) is a purified botulinum neurotoxin type A formulation free from complexing proteins, with proven efficacy and good tolerability for the treatment of several neurological conditions, but with a very limited evidence in the treatment of refractory DO as not yet licensed for the use in the urologic field. The aim of the present study was to compare the efficacy and safety of the two neurotoxins in patients affected by urinary incontinence (UI) due to refractory IDO and NDO.

Fifty-four naïve patients were enrolled in a multicentric, prospective, randomized, study. Patients were randomized 1:1 to receive intradetrusor injections of equal doses of Onabot/A or Incobot/A. Prior to and 8 weeks after injection, patients underwent the recording of the 3-day voiding diary, urodynamics, the Visual Analog Scale (VAS) to score the impact of urinary symptoms on Quality of Life (QoL; 10=worse, 0=best) and the Incontinence-QoL (I-QoL) Questionnaire. Side effects were accurately recorded. Primary end points were change from baseline in daily UI episodes and in VAS scores, and the assessment of reported adverse effects.

Twenty-six pts (10 with NDO and 16 with IDO) received Incobot/A intradetrusor injections, and 28 (12 with NDO and 16 with IDO) underwent Onabot/A intradetrusor treatment. Patients with IDO and those affected by NDO received 100 U or 200 U of Onabot/A or Incobot/A respectively, and intradetrusor injections were performed as usually, under cystoscopic guidance. At 8 wks follow up, urinary symptoms, VAS and I-QoL scores significantly improved in both the 2 groups of patients (Table). Nocturia significantly decreased particularly in IDO patients treated with Incobot/A. UTIs and bacteriuria were detected in 1 and 3 cases treated with Incobot/A and in 5 and 7 cases treated with Onabot/A (p=0.12 and p=0.22, respectively) Overall, post-void residual volume increased, but not significantly in IDO patients.

These preliminary results show the noninferiority of Incobot/A, as compared to Onabot/A intradetrusor injections, in improving urinary symptoms and QoL in patients affected by both IDO and NDO in a short term follow up. Importantly, although in a limited number of patients in our study, our results also show that Incobot/A intradetrusor injections are followed by less episodes of UTIs and bacteriuria as compared to Onabot/A, an effect that can be explained by the different properties of the two neurotoxins. Onabot/A formulation contains the neurotoxin as part of a larger protein complex with accessory proteins that are not required for the pharmacological activity of the neurotoxin. The presence of complexing proteins may facilitate an immunogenic reaction and the development of neutralizing antibodies against the active neurotoxin, leading to partial or complete clinical unresponsiveness. In the Incobot/A formulation, the neurotoxin has been purified so that it is free from complexing proteins and thus exhibits a high specific biological activity. That complexing proteins can induce an inflammatory response has recently been demonstrated in a human neuroblastoma cell line; in addition, the complexing proteins are also responsible for an increased release of multiple inflammatory cytokines in the injected tissues. These effects have not been described with Incobot/A.

Incobot/A and Onabot/A intradetrusor injections are both effective and safe in improving urinary symptoms and QoL in patients with IDO and NDO, in a short term follow up. The more significantly reduction in frequency of nocturia and the lower frequency of UTIs and bacteriuria in patients treated with Incobot/A could be linked to the different pharmacological properties of this neurotoxin, and to a limited ability to induce an inflammatory response in the injected tissues. These effects need to be confirmed in a larger number of patients and with additional prospective, randomized studies.