Botulinum treatment benefits in BPH maybe down to placebo effect

By Sally Robertson, B.Sc.Oct 17 2012

Treatment with botulinum toxin has proved no more effective than placebo at reducing symptoms in men with lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), show study findings.

Reductions in the International Prostate Symptom Score (IPSS) were not significantly greater with active treatment than with placebo for any treatment dose (100, 200, or 300 U) of onabotulinumtoxinA, owing to an unexpectedly pronounced placebo effect in the study, report Michael Marberger (Medical University of Vienna, Austria) and colleagues.

The use of botulinum toxins for the treatment of LUTS/BPH has been explored as a minimally invasive alternative for men who have not responded to oral therapies and/or who do not want surgery. However, almost all trials have been small and only one has been placebo controlled, says the team.

"This placebo-controlled randomized, multicenter phase 2 dose-ranging study is the largest study performed to date to investigate the use of onabotulinumtoxinA for the treatment of patients with moderate to severe LUTS/BPH," write Marberger and colleagues in European Urology.

In a population of patients, aged at least 50 years, and with an IPSS of 12 or more, a total prostate volume (TPV) of 30 to 100 mL, and a maximum urine flow rate (Q_max) of 5 to 15 mL per second, significant improvements from baseline in IPSS were observed in all groups from weeks 2 through 72.

However, there was a pronounced placebo response, with no statistically significant differences between onabotulinumtoxinA groups and placebo at any time point during the study, say the researchers.

There were also significant improvements in Q_max, TPV, and total transition volume (TZV), again with no significant differences between the active treatment and placebo groups observed.

As most other published studies of botulinum toxins in LUTS/BPH have been performed in patients previously treated with α-blockers, the team performed a post-hoc analysis in a subgroup of 180 patients who had previously received α-blockers and were washed out for the treatment over 15 days prior to the study.

Interestingly, there was a significant reduction from baseline in IPSS in the 200 U onabotulinumtoxinA group compared with placebo, of 6.6 points versus 3.5 points.

"Some patients in the subgroup may have achieved some treatment benefits with prior therapy, and the memory of this effect may have improved the ability to differentiate between active drug and placebo, thus leading to a lower placebo response," suggest Marberger et al.

Additional placebo-controlled studies in an appropriate target population of patients are needed to confirm these findings, say the researchers, who note that it has been suggested that interventional therapy may itself lead to a higher than expected placebo effect.

It has also been suggested that a placebo surgical intervention may induce a perception of clinical benefit in the patient solely through the actions associated with the treatment such as physician interaction, high benefit expectation, and surgical procedure, they add.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.