Neuromodulation of the Peroneal Nerve Safe for Overactive Bladder

Electrical transcutaneous neuromodulation (eTNM) of the peroneal nerve led to fewer side effects compared with solifenacin (Vesicare) in the treatment of overactive bladder, a randomized trial showed.

Among 76 treatment-naive women randomized 2:1 to peroneal eTNM or solifenacin, 12% versus 48% reported a treatment-related adverse event (TRAE; P<0.001), reported Jan Krhut, MD, PhD, of University Hospital in Ostrava, Czech Republic, and colleagues.

“Due to its noninvasiveness, very good tolerability, ease of use, and suitability for home-based treatment, peroneal eTNM could be considered in the OAB [overactive bladder] treatment algorithm prior to sacral neuromodulation or intravesical botulinum toxin injections,” Krhut and team wrote in the Journal of Urology.

The most frequently reported TRAEs in the eTNM group were transient erythema at the stimulation point (n=2) and transient discomfort/pain at the stimulation point (n=2). However, using a 100-point scale, median patient-rated pain intensity scores reported at any study visit did not exceed 9 points.

“Given that a score of 30 points is accepted as the cutoff between mild and moderate pain and the reported visual analog scale scores did not exceed 10 points in most patients, peroneal eTNM can be considered painless,” Krhut and colleagues wrote.

Moreover, the most common TRAE in the solifenacin group — dry mouth in 32% of patients — persisted over the entire treatment period in most cases.

While the study wasn’t designed to compare efficacy variables, peroneal eTNM was as effective as solifenacin in the majority of assessed efficacy endpoints, Krhut’s group noted. “Importantly, in post hoc analyses, both groups showed a significant improvement after 12 weeks of treatment in all efficacy endpoints.”

The proportions of treatment responders in the peroneal eTNM group compared with the solifenacin group were:

• 87% vs 74% for Patient Perception of Intensity of Urgency Scale (PPIUS) grade 3 urgency episodes
• 87% vs 75% for PPIUS grade 3+4 urgency episodes
• 90% vs 94% for urgency incontinence
• 92% vs 94% for any incontinence episodes

“Since severe urgency is considered a key symptom of OAB, its improvement is of great clinical importance,” the authors wrote.

In an editorial accompanying the study, Ly Hoang Roberts, MD, of the Cleveland Clinic Foundation and Glickman Urological and Kidney Institute in Cleveland, and Kenneth M. Peters, MD, of Oakland University William Beaumont School of Medicine in Royal Oak, Michigan, praised the study authors for seeking to improve symptoms of overactive bladder with a minimally invasive target that can be used at home, adding that the study “suggests that the peroneal nerve may be that target.”

However, they noted that previous animal studies have had conflicting results on the peroneal nerve as a target, and pointed out that there is a known placebo effect associated with neurostimulation.

Thus, “either a sham-controlled trial by choosing an alternative electrode placement on the lower extremity or a randomized trial comparing posterior tibial nerve stimulation to eTNM of the peroneal nerve would help elucidate, and perhaps solidify, the authors’ findings,” they wrote. “This would give the clinician confidence that modulating the peroneal nerve is effective for the treatment of OAB.”

This multicenter study randomized 77 women; the safety analysis involved 76 patients, while the full analysis included 72 patients. All patients were white, with a median age of 53 in the eTNM arm and 54 in the solifenacin arm.

Patients were randomized 2:1 to 12 weeks of treatment with daily peroneal eTNM using the URIS neuromodulation system or solifenacin 5 mg. Those in the eTNM group were treated at their home (the URIS device is attached to the mid thigh, connected to the ground and active electrodes) once daily for 30 minutes.

Stimulating the peroneal nerve causes a visible motor response “in the form of rhythmic feet movement in the transversal plane defining the optimal neuromodulation point,” Krhut and colleagues explained. “Fully noninvasive, highly selective nerve stimulation and continuous adjustment of the stimulation parameters during stimulation represent the main advantages of peroneal eTNM compared with the other methods used for peripheral neuromodulation.”

They also noted that the “excellent tolerability” in the peroneal eTNM group corresponded with the greater improvement in quality of life as measured using the European Quality of Life-5 Dimensions questionnaire and the European Quality of Life 5 Dimensions visual analog scale score compared with the solifenacin group.

Krhut and team acknowledged some limitations to their study, including heterogeneous baseline group characteristics, the absence of an option of dose escalation in the solifenacin group, and the absence of long-term follow-up.