FormalPara Key Summary Points

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI).

Percutaneous tibial nerve stimulation (PTNS) is a safe and effective therapy for UUI and OAB, however patient compliance is limited by the need for weekly office visits and subsequent maintenance therapy.

Implantable devices have been developed to deliver the same therapeutic mechanism of action as PTNS using permanent implanted devices that provide at-home stimulation.

There is a large body of high-quality evidence for tibial nerve stimulation (TNS) in the treatment of UUI and OAB, including several randomized controlled trials of PTNS, which demonstrate clinical effectiveness.

Because percutaneous and implantable approaches stimulate the same target nerve with the same mechanism of action, data from randomized trials of PTNS are applicable to implantable TNS devices.

Introduction

Overactive bladder (OAB) is defined by the International Continence Society (ICS) as “urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with urinary incontinence (OAB-wet) or without (OAB-dry), in the absence of urinary tract infection or other detectable disease” [1]. OAB is a chronic condition requiring long-term treatment, with symptoms that cause a significant degree of bother and negatively impact quality of life [2]. OAB affects 12–16% of the adult population [3, 4] with an estimated cost of $82.6 billion in 2020 [5], although the actual prevalence of OAB may be even higher due to the known cultural stigma which likely obscures the true prevalence [6, 7]. Approximately one-third of patients with OAB have urge urinary incontinence (UUI) [4], which is defined by the ICS as the “complaint of involuntary loss of urine associated with urgency” [8]. Clinical practice guidelines from the American Urological Association (AUA)/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) position behavioral therapies as first-line treatment, followed by second-line pharmacologic management, and then third-line options of onabotulinumtoxinA (BTX-A) injections, percutaneous tibial nerve stimulation (PTNS), and sacral nerve stimulation (SNS) [9]. It is estimated that fewer than 5% of patients progress to third-line OAB therapies given barriers of invasiveness, access, and/or burden [10]. While PTNS can be an attractive option due to its favorable safety and efficacy profile, issues such as low therapy adherence have led to the development of implantable tibial nerve stimulation (ITNS) devices intended to provide the same mechanism of action for tibial nerve stimulation (TNS) that once implanted, deliver the same target stimulation to the patient at home rather than requiring repeated visits to a clinic.

Among clinical trial designs, randomized controlled trials (RCTs) are considered the highest level of evidence [11]. The aim of this review is to provide an overview of TNS and summarize the foundation of high-level evidence demonstrating the efficacy of TNS for treating OAB and associated symptoms, including UUI. This high-level evidence has been generated from several RCTs of PTNS and additional studies on ITNS published in peer-reviewed journals. The PTNS RCTs are informative for ITNS technologies that utilize the same mechanism of action to deliver TNS. This review also briefly discusses clinical data available from ITNS technologies, which reflect the comparable results achieved for PTNS and ITNS.

TNS—Mechanism of Action

The storage and elimination of urine depends on coordination between the bladder and urethral sphincters, which is mediated by central nervous system pathways [12]. The micturition reflex requires efferent pathways from the spinal cord to the bladder, as well as afferent input from the bladder to the spinal cord [13]. The pelvic floor muscle, bladder sphincters, and bladder muscle are controlled by the lumbar-sacral nerves (L4-S3).

OAB, including UUI, is characterized by escalated detrusor muscle activity, urethral sphincter activity, and an increase in bladder contractions. The latter can result from afferent overactivity prior to adequate fluid volume in the bladder. The increased stretch or isovolumic response of the bladder, i.e., afferent activity, results in increased bladder contractions, resulting in the urge to void the bladder [14, 15] and is the target of neuromodulation OAB therapy. Electrical stimulation of the sacral nerves (particularly S3) has been shown to modulate brain-bladder communication, leading to improvement in bladder dysfunction [12]. This is the basis of SNS therapy for OAB [16, 17], in which an implantable neurostimulator placed in the upper buttock delivers stimulation via a connected lead that is placed through the sacral foramen with the lead electrodes in proximity to the sacral nerve.

Another established nerve target for modulation of brain/bladder communication is the posterior tibial nerve, which originates from the lumbar-sacral nerves, is a continuation of the sciatic nerve, and can be accessed approximately 3–4 cm from the medial malleolus [15, 18]. TNS in animal models has been shown to inhibit the rhythmic isovolumic contractions [19] through inhibition of afferent nerve activity [20, 21], enabling the bladder capacity to increase prior to the urge to void. This effect has been shown to have prolonged post-stimulation inhibition of bladder activity via the afferent nerves [19].

Stimulation of the tibial nerve delivers stimulation to the sacral nerves that control bladder function [22]. Because the tibial nerve is a more distal nerve and comprised of L4, L5, S1, S2 and S3, stimulating at this nerve target results in increased afferent signaling through these nerve roots to the spinal cord and brain and may result in a more robust clinical response than S3 alone. Additionally, because the tibial nerve is a more accessible nerve target than the sacral nerves, TNS allows modulation of nerves innervating the pelvic floor via a less invasive approach than SNS. TNS approaches include transcutaneous TNS, PTNS, and ITNS; this article focuses on PTNS, a guideline-recommended therapy, and ITNS, a newer approach to delivering TNS.

PTNS

PTNS uses an external neurostimulator to deliver stimulation through a 34-gauge needle inserted percutaneously approximately 5 cm cephalad to the medial malleolus and 2 cm posterior to the tibia. Correct positioning of the needle electrode is confirmed by a motor response (toe flexion or fan, or extension of the entire foot) and/or sensory response (tingling sensation across the heel or bottom of the foot). A constant voltage, square wave with a duration of 200 microseconds and a rate of 20 Hz is delivered continuously. Therapy is administered in a clinic setting and typically consists of 30-min sessions administered weekly for 12 weeks. If the patient exhibits a therapeutic response, this can be followed by less frequent maintenance therapy sessions every 3–4 weeks; however, the optimal maintenance regimen remains undefined and may vary among patients. This uncertainty around the optimal maintenance protocol is a key limitation of PTNS. Two PTNS systems are commercially available in the United States, Urgent PC (Laborie) and NURO (Medtronic). PTNS is intended to treat patients with OAB and associated symptoms of urinary urgency, urinary frequency, and urge incontinence. While these systems are contraindicated for patients with nerve damage that could impact either tibial nerve or pelvic floor function, some studies have demonstrated successful treatment of OAB symptoms with PTNS in patients with neurogenic conditions such as multiple sclerosis [23]; however, this review will focus on non-neurogenic OAB as there is currently no commercially available neuromodulation system approved for use in patients with neurogenic OAB.

While the AUA/SUFU guideline classifies PTNS as a third-line therapy, it also acknowledges that patients should not be required to go through each line of treatment in order [9]. PTNS has been shown to be safe and effective in drug-naïve patients [24], and some guidelines position PTNS earlier in the OAB care pathway. The European Association of Urology recommends PTNS as a conservative option before medications [25], and several publications highlight the favorable safety profile of PTNS compared to BTX-A and SNS [26, 27] and indicate that PTNS could be offered before BTX-A or SNS in a step-by-step algorithm from least to most invasive [28]. However, PTNS poses a burden on patients who must return to the clinic weekly for therapy sessions (or monthly, or more frequent, for maintenance therapy or to the extent their health plan will allow). This high burden compared to other treatment options impacts therapy adherence, preventing some patients from attaining or sustaining clinical benefit. In a large retrospective study, it was found that only a quarter (26%) of the patients were able to complete all 12 sessions. Furthermore, less than half (46%) of these patients chose to continue with the therapy in the long term [29]. In another retrospective study, 53% of patients who completed the initial 12 weeks of treatment ultimately discontinued therapy within 1 year [30]. One study found that over 40% of patients discontinued therapy for nonmedical reasons [31]. This high attrition rate of PTNS prompted development of alternative peripheral nerve stimulation systems that require less patient burden to engage in treatment. Long-term adherence has also been demonstrated to be a challenge with oral OAB medications [32, 33], underscoring the broader need for new treatment options that may improve therapy adherence in this patient population [34].

ITNS

Given the limitations of PTNS, ITNS devices have been and are continuing to be developed to provide additional options for patients that can improve adherence and access to prescribed treatment, and that may allow for personalized medicine by adjusting the dose based on patient need, thus potentially leading to more positive patient outcomes. ITNS options also present reduced logistical burdens for patients and providers compared to PTNS and a less invasive procedure than SNS.

At the time of publication, two ITNS devices have received Food and Drug Administration (FDA) authorization for marketing for treatment of UUI: eCoin (Valencia Technologies) and Revi (BlueWind Medical); the reader is referred to other publicly available documents for descriptions and images of these devices [35,36,37]. In addition, clinical trials are ongoing for investigational ITNS devices from Medtronic, Coloplast, Uro Medical, and BioNess. ITNS systems utilize a small neurostimulator implanted above or below the fascia in the area of the tibial nerve, powered by either an internal battery (primary cell or rechargeable) or an external power source, paired with some type of control device to adjust stimulation. As with PTNS, stimulation of the target nerve is confirmed by observance of a motor or sensory response. Internally-powered ITNS devices automatically deliver intermittent stimulation, similar to the model of PTNS but with minimal to no patient adherence or compliance concerns and without the need for frequent and ongoing office visits. In the eCoin pivotal trial, stimulation parameters were equivalent to those of PTNS, with a pulse width of 200 microseconds and frequency of 20 Hz, and stimulation was delivered for 30 min every 3–4 days [38]. Similarly, in the ongoing Medtronic pivotal trial, the recommended stimulation paradigm is 30 min every other day (frequency 20 Hz, pulse width 200 microseconds) [39] whereas the Coloplast pivotal trial stimulates for 30 min per day for 2 weeks, followed by 30 min per week.

PTNS has been used in the treatment of OAB, and its symptoms, such as UUI, for over 15 years [40] and is supported by a large body of high-quality evidence, including several RCTs (reviewed below). While ITNS uses an implantable approach that is distinct from the percutaneous approach, these implantable devices deliver therapeutic nerve stimulation to the same target nerve through the same mechanism of action as PTNS technologies; therefore, published clinical data regarding the safety and efficacy of PTNS for treatment of OAB are relevant to assessments of safety and efficacy for ITNS. This review focuses on RCTs of TNS in OAB, including UUI, in light of the labeling for currently available ITNS devices that have received FDA market authorization to date (eCoin [41], Revi [37]), which are indicated for use in certain patients with UUI.

Methods

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. A comprehensive search of the Medline and Embase databases was conducted to identify RCTs of PTNS for OAB and its associated symptoms published from January 1, 2000, through October 31, 2023. Search terms included PTNS therapy keywords, indication keywords, and PTNS brand names and model numbers (Table 1). The search was limited to human RCTs and English language only. Selection criteria for article review included RCT of PTNS vs. sham or a guideline-recommended treatment in an OAB and/or UUI population that is consistent with labeling for ITNS. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of the search results and article selection is shown in Fig. 1. The search resulted in 38 articles including 1 duplicate, leaving 37 articles. After abstract review, 27 records were excluded (Fig. 1). The full text of the remaining 10 articles were reviewed, and all 10 were selected for inclusion in the qualitative synthesis.

Table 1 Literature search terms
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Fig. 1
figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram. RCT randomized controlled trial, PTNS percutaneous tibial nerve stimulation, OAB overactive bladder

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Results

The comparator arms in the included studies were sham (n = 4), conservative therapy (n = 1), oral medications (n = 4), and BTX-A injections (n = 1). These studies are summarized in Table 2.

Table 2 Summary of randomized controlled trials (RCTs) comparing percutaneous tibial nerve stimulation (PTNS) vs. sham or guideline-recommended therapy for overactive bladder (OAB)
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PTNS vs. Sham

Four studies reported on RCTs of PTNS vs. sham, using different methods to deliver sham treatment. All four studies demonstrated that PTNS performed better than sham therapy. In 2009, Finazzi-Agrò et al. investigated the mechanism of action of PTNS for OAB in an RCT [42]. In the sham group, the needle was inserted in the gastrocnemius muscle and stimulation was delivered for 30 s and then turned off. PTNS subjects (n = 16) and sham subjects (n = 8) underwent 12 30-min sessions (3 sessions per week for 4 weeks). While the focus of the study was on evoked potentials, the authors also reported efficacy results. In the PTNS group, 62.5% of subjects were considered responders (defined as ≥ 50% reduction in urgency episodes); no patients in the sham group were responders. Quality of life was significantly improved only in the PTNS group. Safety results were not reported.

In 2010, Peters et al. reported the results of the Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT), a large, multicenter, double-blind RCT [43]. A total of 220 patients with OAB were randomized 1:1 to 12 weeks of weekly PTNS or sham. The sham treatment utilized a placebo needle paired with transcutaneous electrical nerve stimulation (TENS) surface electrodes, giving the sensation of stimulation without delivering active therapy at the tibial nerve. In the primary analysis, 54.5% of PTNS subjects and 20.9% of sham subjects (p < 0.001) reported that their overall bladder symptoms were moderately or markedly improved. PTNS was statistically significantly superior to sham in reducing frequency, UUI, nighttime voids, and urgency. OAB Quality of Life Questionnaire (OAB-q) symptom severity and quality of life scores were statistically significantly improved in the PTNS group compared to sham. Local treatment related adverse events in the PTNS group were minor and occurred in less than 3% of patients. Specific data on adverse events included ankle bruising (1/110, 0.9%), tingling in the leg (1/110, 0.9%), discomfort at the needle site (2/110, 1.8%), and bleeding at the needle site (3/110, 2.7%); none were reported in the sham group.

Finazzi-Agrò published another single-center, double-blind, sham-controlled RCT in 2010, again using a needle inserted into the gastrocnemius muscle as sham [44]. Subjects with detrusor overactivity incontinence were randomized to either PTNS (n = 18) or sham (n = 17). Thirty-minute sessions were administered 3 times a week for a total of 12 sessions. Of 17 PTNS subjects who completed the study, 12 (71%) were therapy responders, while none of 15 sham subjects who completed the study were responders (p < 0.001). The number of incontinence episodes/day, voids/day, voided volume, and incontinence quality of life (I-QoL) score improved significantly in the PTNS group but not the sham group. Patients in both groups reported occasional transient pain at the stimulation site; no serious side effects were reported.

Most recently, in 2021, Lashin et al. examined a shortened 6-week treatment protocol in an RCT of PTNS (n = 25) vs. sham (n = 25) [45]. The sham consisted of inserting the needle electrode as in the PTNS group but without any current. All subjects received 6 weekly 30-min sessions. The PTNS group demonstrated significant improvement in the OAB Symptom Score (OABSS) at 7 weeks, 3 months, and 6 months compared to sham (p = 0.001). Voiding diaries were improved at 7 weeks in 52% of PTNS subjects vs. 0% of sham subjects (p < 0.001), and the improvement in diary parameters in the PTNS group vs. sham was maintained through 6 months. On a 1-h pad test, there was not a significant difference between groups. Local adverse events occurred in 28% of PTNS subjects and 16% of sham subjects.

PTNS vs. Conservative Therapy

Pelvic floor muscle training (PFMT) is a first-line behavioral therapy for OAB. One article described an RCT of PTNS vs. PFMT with vaginal electrical stimulation (ES) in 60 women with OAB [46]. The ES + PFMT arm consisted of an initial 10 sessions of ES followed by PFMT with a physiotherapist. Following these sessions, subjects continued PFMT at home for 6 months. Subjects in the PTNS arm received PTNS twice a week (30 min each) for 6 weeks. Compared to baseline, there were statistically significant improvements in number of micturitions per day, nocturia, and UUI in the PTNS arm but not the ES + PFMT arm; voided volume improved significantly in both groups. When comparing groups, improvements in nocturia, UUI, and voided volume were significantly greater for PTNS than ES + PFMT. Improvements in quality of life (OAB-q Short Form (SF)) and urgency (Patient Perception of Urgency Scale), as well as the Patient Global Impression of Improvement (PGI-I), were also significantly greater in the PTNS group. No significant side effects were observed in either arm. PTNS performed better than conservative therapy, specifically vaginal ES followed by pelvic floor muscle training with a therapist.

PTNS vs. Oral Medications

Four articles described RCTs of PTNS vs. anticholinergic oral medications. In 2009, Peters et al. published the results of the Overactive Bladder Innovative Therapy trial (OrBIT), a multicenter RCT that compared the effectiveness of PTNS to extended-release tolterodine [47]. Subjects with urgency-frequency (n = 100) were randomized 1:1 to PTNS (12 weekly sessions of 30 min) or 4 mg daily tolterodine. The primary end point was reduction in voids/day. On voiding diaries, all symptoms were significantly improved within each group at 12 weeks; comparisons between groups were not statistically significant. The primary end point of reduction in voids/day was not significantly different between groups. On the Global Response Assessment (GRA), the proportion of subjects reporting improvement or cure was significantly greater for PTNS (79.5%) vs. tolterodine (54.8%) (p = 0.01). Quality of Life (OAB-q) improved significantly in both groups, with no significant difference between groups. Treatment-related adverse events occurred in 16.3% of PTNS and 14.3% of tolterodine subjects.

Vecchioli-Scaldazza et al. conducted a randomized controlled crossover study of PTNS vs solifenacin succinate (SS) in 40 women with OAB [48]. Group A received SS 5 mg daily for 40 days, followed by a 3-month washout period before receiving PTNS (30-min sessions twice a week for 6 weeks), and Group B followed the opposite schedule. The primary endpoint was reduction in voids/day. Improvements in voids/day and other voiding symptoms (nocturia, UUI, voided volume) were statistically significant in both groups for both treatments. Similarly, both groups demonstrated significant improvements in urgency (Patient Perception of Intensity of Urgency Scale, PPIUS) and quality of life (OAB-q SF) for both treatments. Safety results were not provided.

In 2015, Preyer et al. published an RCT of PTNS vs tolterodine in 36 women with OAB [49]. PTNS was delivered in weekly 30-min sessions for 3 months, and tolterodine was prescribed at 2 mg twice daily. The primary outcome measure was the difference in micturitions per 24 h. At 1 and 3 months, micturition frequencies did not significantly improve in either arm; however, incontinence episodes in 24 h decreased significantly in both groups at 3 months. Quality of life (using a GRA with visual analogue scale) was significantly improved in both groups at both timepoints. Side effects were reported in 17% of PTNS subjects and 50% of tolterodine subjects.

In 2017, Vecchioli-Scaldazza and Morosetti reported on an RCT of 105 women with OAB who were randomized to PTNS (30 min weekly for 12 weeks), SS (5 mg daily for 12 weeks), or PTNS + SS (PTNS 30 min weekly for 8 weeks and SS 5 mg on alternate dates for 8 weeks) [50]. OAB symptoms were assessed using the OABSS. At follow-up, symptom scores for day-time frequency, night-time frequency, urgency, and UUI were significantly improved compared to baseline in all 3 groups. In comparing the change in symptoms across treatment groups, all symptoms were significantly more improved with PTNS + SS than with SS alone. Urgency and UUI were also more improved with PTNS + SS vs. PTNS alone. Quality of life (OAB-q SF 13) was significantly improved in all groups, and the improvements were significantly greater for PTNS + SS vs. either treatment alone; similar results were obtained with OAB-q SF 6. Over a longer follow-up of 10 months, improvements in OAB-SS persisted for 0.9 months for SS, 2.5 months for PTNS, and 5.9 months for PTNS + SS. Safety results were not reported. In summary, PTNS demonstrated similar efficacy to oral OAB medications.

PTNS vs. BTX-A Injection

One study examined PTNS vs. intradetrusor injection of BTX-A. Sherif et al. reported on an RCT of intradetrusor BTX-A injection (100 U) vs. PTNS (30 min once a week for 12 weeks) in 60 patients with OAB followed for 9 months [51]. Subjects in the BTX-A group had significant improvements in OAB-SS, urgency, and quality of life, as well as symptoms of frequency, nocturia, and leaks, at all timepoints. For PTNS, quality of life improvements were significant at all follow-up visits through 9 months, while OAB-SS and urgency were significantly improved through 6 months. Frequency, nocturia, and leaks were significantly improved through 6 months and post-void residual (PVR) was significantly improved through 3 months for PTNS. Comparing groups, the improvements in OAB-SS, urgency, and quality of life were significantly greater for BTX-A than PTNS at the 6-week and 9-month visits; improvements in frequency, nocturia, and leaks were also significantly greater for BTX-A at some visits. Increases in PVR were significantly greater for the BTX-A group compared to PTNS at all timepoints; 2 patients receiving BTX-A with PVR > 200 mL required clean intermittent catheterization. Early post-operative mild hematuria occurred in 10% of subjects receiving BTX-A and urinary tract infection in 6.6%. Local adverse events in the PTNS group included minor bleeding and temporary painful sensation. BTX-A treatment performed better than PTNS, with differing associated adverse events.

Pivotal Trial Data for ITNS

The eCoin device (Valencia Technologies) [38] was evaluated in a multi-center, prospective, open-label, single arm trial involving 133 subjects with refractory UUI. The devices were activated approximately 4 weeks after implant, and automated stimulation sessions then occurred for 30 min every 3 days for 18 weeks and every 4 days thereafter. In the primary efficacy analysis, 68% of subjects experienced ≥ 50% reduction in UUI episodes at 48 weeks post-activation in the Intent to Treat population, and 75% of subjects experienced a ≥ 50% reduction in UUI episodes at 48 weeks post-activation in the per-protocol population [35, 36]. These results are consistent with an earlier feasibility study of eCoin, in which 69.6% of subjects experienced ≥ 50% reduction in UUI episodes at 3 months [52].

In the pivotal trial, there was only one related serious adverse event of a procedure-related infection resulting in explant; this event resolved without additional sequelae. Overall, and including the one explanted device adverse event, device- or procedure-related adverse events occurred in 19% of subjects through 52 weeks post-implant. Related events occurring in ≥ 5% of subjects included implant site infections (7%), and device related issues involving stimulation, migration, or device malfunction (7%). Other related events occurring less commonly included erythema at implant site, pain at the implant site (4%), extremity pain, discomfort (2%), implant site swelling, discomfort (2%), skin dermatitis, skin irritation (2%), and anal incontinence (1%). When considering the safety data reported and compared to the safety data for PTNS, erythema, pain, discomfort, and infection are adverse events which are not unexpected for an implantable device. Overall, there are no new safety signals related to the ITNS therapy itself. Results from the eCoin pivotal trial suggest that the events associated with ITNS can be attributed to the differences between implantable versus percutaneous TNS procedures. eCoin ITNS therapy is clinically effective in the treatment of UUI, with acceptable risks associated with an implantable device.

Regarding the BlueWind Revi device mentioned earlier in this article as one of two FDA authorized devices for administering ITNS, there has not yet been a journal publication on the results of the Revi pivotal trial. According to clinicaltrials.gov (NCT03596671), the pivotal trial is a prospective, multi-center, single arm, open-label study of patients with UUI. The primary endpoints are improvement in UUI episodes at 6 months and incidence of adverse events at 12 months.

Pivotal trials are ongoing for ITNS devices from Medtronic and Coloplast. Study information is available on clinicaltrials.gov. Medtronic’s prospective, multicenter, open-label pivotal study enrolled patients with UUI, and the primary outcome measure is the proportion of patients with ≥ 50% reduction in daily UUI episodes at 6 months (NCT05226286) [39]. Coloplast is conducting a prospective, randomized (therapeutic vs. non-therapeutic stimulation), double-blind, multicenter pivotal trial in subjects with UUI; the primary outcome measures are the response rate (defined as ≥ 50% reduction in UUI episodes between therapeutic and non-therapeutic stimulation at 3 months and ≥ 50% reduction in UUI episodes in the therapeutic group at 12 months) (NCT05250908). These trials, along with other ongoing studies of the eCoin device by Valencia (NCT05685433 and NCT05882318) and of the Revi device by Bluewind (NCT06217328) will contribute further to the growing body of evidence for ITNS.

Discussion

This article summarizes the large body of high-quality evidence for TNS as a treatment for OAB and associated symptoms, including evidence established by RCTs of PTNS vs. sham or other guideline-recommended therapies for OAB, including PFMT, medications, and BTX-A injections. A limitation of this review is that none of the included publications reported effect size, which is a useful indicator of the magnitude of the differences observed at follow-up compared to baseline. Although there are also many studies demonstrating the safety and efficacy of SNS for OAB, SNS is not a focus of this review given the lack of RCTs comparing SNS vs. PTNS. Another limitation of this article is that it is not designed as a systematic review. As a narrative review, a comprehensive literature search strategy and PRISMA methodology were utilized to ensure transparent reporting of the article selection process. In addition to the PTNS RCTs highlighted in this review, many other publications continue to demonstrate the efficacy and safety of PTNS for OAB [53].

PTNS and ITNS deliver neuromodulation through the same mechanism of action via the tibial nerve, making available published clinical data from PTNS relevant to ITNS. With the aging population and increasing burden of this disease state, patients and clinicians are interested in safe and effective alternatives to oral medications as the evidence that anticholinergic medications are associated with dementia and cognitive changes is accumulating [54]. The high-quality evidence supporting PTNS and ITNS is compelling and key to offering patients an alternative treatment option for OAB and UUI that is safe and effective.

Clinical Perspective

The prevalence of OAB highlights the need for therapeutic solutions that offer patients relief from their symptoms. As the effects of OAB broadly increase, patient quality of life is inversely affected [55]. Currently, many of the main pharmaceuticals used to treat OAB and associated symptoms, have been linked to adverse side effects, with recent reports that anticholinergic medications have been associated with increased risk of dementia [56]. Further, other therapies have challenges with patient compliance, which has been reported as low as 39.5% after 1 year for PTNS [57]. OAB is a chronic condition which requires adjustment and long-term therapy. The currently established therapeutic options will continue to advance and modernize to better meet patients’ needs. There is also interest in the future potential for personalized treatment based on patient phenotyping [58]. Given there are no publications to date regarding the cost effectiveness of ITNS, an economic comparison of ITNS compared to other OAB treatment options is not currently available. As evidenced here, the tibial nerve is an established therapeutic target with limited side effects; however, patient compliance with currently available TNS systems is required to ensure therapy delivery. Innovative integrated ITNS therapeutic options can address patient compliance challenges, and allow for the potential of modulation with disease progression.

Conclusions

RCTs of PTNS have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Given the equivalent mechanism of action and shared nerve target utilized by ITNS, data for these RCTs can be considered foundational high-level evidence supporting the efficacy of ITNS for treatment of OAB and UUI in particular. As demonstrated by the eCoin feasibility study and pivotal trial results, the safety profile of ITNS differs from that of PTNS due to the addition of adverse event types specific to the implantable device and procedure. ITNS technology has demonstrated positive efficacy results and patient outcomes. Given that ITNS eliminates the burden of weekly clinic visits, it represents an attractive, minimally invasive, patient-centered approach of targeting the tibial nerve to deliver the intended clinical benefit already established for TNS. With ITNS, there is also potential for improved adherence, accessibility, and outcomes for patients. ITNS and PTNS offer differing advantages and disadvantages and can ultimately be chosen with the guidance of a clinician based on patient factors and patient preferences. The positioning of ITNS along the OAB care pathway relative to other treatment options is of great interest and yet to be seen pending incorporation of the growing ITNS clinical evidence into professional society guidelines. Given the aging population and increasing burden of this disease state, recognizing the high-quality evidence supporting additional available therapies to treat this chronic condition is critical to advancing the field.