Safety and efficacy of botulinum neurotoxin in the treatment of erectile dysfunction refractory to phosphodiesterase inhibitors: Results of a randomized controlled trial

Abstract

Background: There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation.Objectives: To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). Patients and methods: A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment.Results: Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p < 0.001) compared to the control group. At 6-and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. Conclusion:BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy.

Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin®) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series

“…Since the potency of Botox ® and Xeomin ® is identical, they can be compared using a 1:1 conversion ratio [21]. Studies have repeatedly reported the effectiveness of a 100U dose of onabotulinumtoxinA in difficult-to-treat ED [14,16,17]; therefore, we used the same dose of incobotulinumtoxinA in the present study. The conversion ratio between onabotulinumtoxinA (or incobotulinumtoxinA) and abobotulinumtoxinA is more debated [20].…”

“…The first follow-up assessment was performed 43.5 (34-71) days post-injection. EFdomain score post-injection was 21 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). A total of 28/54 (52%) men responded: their EF domain score was 26 (22)(23)(24)(25)(26)(27)(28)(29), corresponding to an increase of 8 (6-15) points from baseline.…”

“…The treatments for which the response was insufficient were PDE5-Is highest approved dose on demand (sildenafil 100 mg, vardenafil 20 mg, or tadalafil 20 mg) or daily (tadalafil 5 mg) for 43/54 men (80%) and/or PGE1 ICI (mean (SD) dose 42 (20) µg for 12/54 men (22%)). The median baseline EF domain score on treatment, i.e., prior to incobo-tulinumtoxinA ICI was 13 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The severity of ED on pharmacological treatment prior to incobotulinumtoxinA ICI according to EF-domain score [19] in the 54 participants was mild, moderate, and severe in respectively 22 (41%), 13 (24%), and 19 (35%) men.…”

“…Three men were not assessed after the 2nd injection. For the 17 men who were assessed at the time of the 2nd injection, the EF score was 18 (16)(17)(18)(19)(20)(21) points and increased to 27 (21)(22)(23)(24)(25)(26)(27)(28)(29) points 35 (29-37) days post 2nd injection (their EF score at baseline was 17 [12][13][14][15][16][17][18][19][20][21] points). After the 2nd injection, 13/17 (76%) men responded compared to baseline.…”

“…A growing body of evidence suggests that off-label BoNT/A intracavernosal injections (ICI) can improve erectile function in ED that responds insufficiently to registered pharmacological treatments. The results of preliminary studies suggest that two BoNT/A products, onabotulinumtoxinA (Botox ® ; Allergan Inc., Irvine, CA, USA) and abobotulinum-toxinA (Dysport ® ; Ipsen, Slough, UK/Galderma, Paris, France) may effectively treat this condition [13][14][15][16][17]. OnabotulinumtoxinA and abobotulinumtoxinA formulations contain the neurotoxin as part of a larger protein complex with complexing (accessory) proteins that are not required for the pharmacological activity of the neurotoxin.…”