ARTISAN-SNM: Rechargeable Sacral Neuromodulation for Urgency Urinary Incontinence
ARTISAN-SNM was a prospective, multicenter, single-arm pivotal study of the rechargeable Axonics sacral neuromodulation system, implanted in one nonstaged procedure without an external test phase, in 129 adults with urgency urinary incontinence. At 6 months, 90% were responders (at least 50% fewer urgency incontinence episodes) and daily episodes had fallen from 5.6 to 1.3.[1]
- Design and population
- Prospective, multicenter, single-arm, unblinded pivotal study. Adults aged 21 or older with urgency urinary incontinence for at least 6 months (at least four leaks on a 72-hour diary, at least half associated with urgency), excluding stress or mixed incontinence, mechanical obstruction and bladder pain syndrome; 129 implanted (age 59.3 years, range 21 to 86; 98% women).
- Arms
- Rechargeable Axonics sacral neuromodulation system implanted in one nonstaged procedure
- Report and follow-up
- 2019 · 6 months after implant
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| 6-month responder rate (at least 50% fewer urgency incontinence episodes on a 3-day diary), all implanted patients, as-treated | 90% | — | Met |
Harms: Serious device-related adverse events: None; Device-related and procedure-related adverse events through the 2019-01-18 data lock: 13/129 (10.1%) with device-related events; 13/129 (10.1%) with procedure-related events (15 events)
Design
Eligible adults were 21 or older with urgency urinary incontinence for at least 6 months, shown on a 72-hour diary as at least four leaks, at least half of them associated with urgency, and at least one leak in each 24-hour period. Men needed a peak flow above 15 mL/s and a residual volume below 150 mL. Stress or mixed incontinence, mechanical obstruction such as prostatic enlargement or urethral stricture, and interstitial cystitis or bladder pain syndrome were exclusions.[2] The FDA review reports 153 patients enrolled and 129 implanted, 97 at 15 US sites and 32 at five Western European sites.[3]
The primary effectiveness endpoint was the responder rate in all implanted patients, analyzed as treated, with patients who left the study or had missing data counted as failures. The FDA review describes the test as a one-sided binomial comparison of the responder rate against 50%.[3] Secondary measures were the 3-day diary, the ICIQ-OABqol quality-of-life score (a 10-point change is the minimal important difference) and a satisfaction questionnaire.[3][4] The registry lists the responder rate with a 2-year time frame.[2] Axonics sponsored the study.[5]
Results
At 6 months, 90% of implanted patients were responders; mean daily urgency incontinence episodes fell from 5.6 to 1.3 and the ICIQ-OABqol score improved by 34 points.[1] In the FDA analysis of the same endpoint, 116 of 129 patients (89.9%; 95% CI 83.4% to 94.5%) were responders, and the null hypothesis of a responder rate of 50% or lower was rejected (P < 0.0001).[3]
At 1 year, 115 of 129 patients (89%) were responders and daily episodes were 1.4, a 75% reduction. Of the 115 responders, 88 (77%) had a reduction of at least 75% and 29% were dry. Of the 113 patients who were responders at 1 month, 106 (94%) remained responders at 1 year. The ICIQ-OABqol score improved by 34.4 points; 93% were satisfied and 92% would undergo the therapy again, counting missing patients as negative.[4]
At 2 years, 121 of 129 patients completed follow-up. In the completers analysis, 93% were responders (113 of 121), daily episodes were 1.0 (an 82% reduction) and the ICIQ-OABqol score improved by 36.1 points. In the as-treated analysis of all 129, 88% were responders. Among the 113 responders, 93 (82%) had a reduction of at least 75%, 54% had a reduction above 90% and 37% were dry; among the 121 completers, 94% were satisfied and 93% would repeat the therapy.[5]
In a secondary analysis of 124 patients with complete 1-year data, 68.5% were very satisfied, 25.8% moderately satisfied and 2.4% slightly satisfied, and satisfaction tracked the reduction in diary voids and leaks. Nine of the 14 patients who were nonresponders at 1 month were responders at 1 year.[6]
Surgery and treatment delivery
Every patient had the tined lead and the rechargeable neurostimulator placed in one procedure, without an external test phase.[1] The lead was placed under fluoroscopy along S3 (preferred) or S4 following International Continence Society best practice. A response on at least two electrodes at less than 4 mA was required to proceed to full implant, and no patient failed this test.[4] The neurostimulator was placed near the upper buttock.[5] Programming used the intraoperative motor responses and postoperative sensory responses.[4]
Patients were taught to recharge every 1 to 2 weeks with a wireless charger held over the neurostimulator by a belt. At 1 year all 124 patients available could recharge, 89% found it easy and 96% found the frequency and duration acceptable; at 2 years the figures were 100%, 91% and 94%. Sessions lasted under an hour for 88% of patients at 2 years, and 98% went at least 7 days between sessions.[4][5]
Nine patients had passed an external trial before enrollment without a full implant. All nine were responders at every visit, and excluding them left the 2-year responder rates unchanged.[5] Thirteen MRI studies in 12 patients (eight of the body, spine or torso) were followed by no adverse events or lead migrations.[5]
Adverse events
Through the FDA data lock, 13 of 129 patients (10.1%) had device-related events and 13 (10.1%) had procedure-related events (15 events), with no serious device- or procedure-related events. Procedural pain was the most common procedure-related event (4 patients).[3]
At 1 year, 14 of 129 patients (10.8%) had 15 device-related events. Stimulation discomfort in 7 patients (5.4%) resolved with reprogramming, and neurostimulator-site pain in 2 resolved spontaneously. Two patients had lead revisions, for migration and for high impedance with suspected fracture, and efficacy returned in both. Six patients (4.6%) had a surgical intervention, including two explants for lack of efficacy in initial nonresponders. Five patients had left the study, four by system explant (one infection, one pain unrelated to the device, two insufficient efficacy) and one by an unrelated death.[4]
By 2 years, device-related events had occurred in 20 patients (16%) and procedure-related events in 15 (12%), with no unanticipated or serious device- or procedure-related events. Uncomfortable stimulation (11 patients, 9%) was resolved by amplitude adjustment in two and reprogramming in nine. Fourteen surgical interventions were performed in 11 patients (9%): lead revision in three (migration one, high impedance two), neurostimulator revision in four (infection one, pain one, migration or rotation two after abdominoplasty) and explant without reimplantation in five (infection one, pain unrelated to the device one, insufficient efficacy three). Eight patients (6%) left the study before 2 years.[5]
Limitations
The study was unblinded and had no comparator or placebo arm; the 6-month endpoint is a responder rate tested against a fixed 50% threshold.[1][3] Axonics sponsored the study and supported its design, data analysis and writing.[5] Ninety-eight percent of participants were women, and efficacy was measured on 3-day diaries counting urgency incontinence episodes only.[4][5] Published follow-up ends at 2 years; the 15-year design life is the manufacturer's rating.[1]
In conversation
- Builds on InSite (2014). The authors compared responder-rate analysis, neurostimulator-site pain and lead migration with InSite's non-rechargeable InterStim experience.
- Parallel to OASIS (Revi) (2024). Single-arm pivotal study of a newer implanted neuromodulator for urgency incontinence, sacral rather than tibial, judged against a 50% responder goal.
Same setting ROSETTA (2016)
ARTISAN-SNM implanted every patient without an external test phase and counted responders among all implanted patients, with missing data as failures. The authors contrast this with InSite, in which the responder rate was reported only for patients available at follow-up and excluded initial therapy failures and patients who exited the study.[4] ROSETTA's primary outcome was the change in daily episodes in a randomized comparison with botulinum toxin, so its measure differs from the single-arm responder rate here.
Guidelines and approvals
- FDA (November 13, 2019). Premarket approval P180046 covers the Axonics Sacral Neuromodulation System for urinary retention and the symptoms of overactive bladder, including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatments. The effectiveness review combined ARTISAN-SNM with published InterStim literature.[3]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2019-07-26 | 6-month results · primary | — | 6-month responder rate (at least 50% fewer urgency incontinence episodes on a 3-day diary), all implanted patients, as-treated: 90%; — Met Mean episodes per day, baseline to 6 months (mean ± SE): 5.6 ± 0.3 to 1.3 ± 0.2; — ICIQ-OABqol improvement at 6 months (0 to 100 scale): 34 points; — | McCrery R, Lane F, Benson K, et al. "Treatment of Urinary Urgency Incontinence Using a Rechargeable SNM System: 6-Month Results of the ARTISAN-SNM Study." *J Urol.* 2020;203(1):185-192. doi:10.1097/JU.0000000000000458 DOI |
| 2020-04-27 | 1-year results · updated | — | 1-year responder rate (at least 50% fewer urgency incontinence episodes), all implanted patients, as-treated with missing data counted as failures: 89% (115/129); — Descriptive Mean episodes per day, baseline to 1 year (mean ± SE), all implanted patients: 5.6 ± 0.3 to 1.4 ± 0.2; P <0.0001 ICIQ-OABqol HRQL improvement at 1 year (0 to 100 scale): 34.4 points; P <0.0001 Satisfied with therapy; would undergo therapy again, all implanted patients: 93%; 92%; — Able to recharge; found recharging easy; found frequency and duration acceptable, among 124 patients available: 100%; 89%; 96%; — | Benson K, McCrery R, Taylor C, et al. "One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence." *Neurourol Urodyn.* 2020;39(5):1482-1488. doi:10.1002/nau.24376 DOI |
| 2020-12-16 | Satisfaction analysis · secondary | — | Very, moderately and slightly satisfied at 1 year (7-point Likert scale), among 124 patients with complete data: 68.5%; 25.8%; 2.4%; — Descriptive Patients who were nonresponders at 1 month and were responders at 1 year: 9/14 (64%); — Descriptive | Geynisman-Tan J, Mueller MG, Kenton KS. "Satisfaction with a rechargeable sacral neuromodulation system-A secondary analysis of the ARTISAN-SNM study." *Neurourol Urodyn.* 2021;40(1):549-554. doi:10.1002/nau.24596 DOI |
| 2021-01-28 | 2-year results · updated | — | 2-year responder rate (at least 50% fewer urgency incontinence episodes), completers analysis (the report's primary analysis): 93% (113/121 completers); — Descriptive Mean episodes per day, baseline to 2 years (mean ± SE), completers: 5.6 ± 0.3 to 1.0 ± 0.2; P <0.0001 ICIQ-OABqol HRQL improvement at 2 years (0 to 100 scale), completers: 36.1 points; P <0.0001 Satisfied with therapy; would undergo therapy again, among 121 completers: 94%; 93%; — Able to recharge; rated recharging easy; rated it acceptable; sessions under 1 hour; at least 7 days between sessions, among 121 completers: 100%; 91%; 94%; 88%; 98%; — | Pezzella A, McCrery R, Lane F, et al. "Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system." *Neurourol Urodyn.* 2021;40(2):714-721. doi:10.1002/nau.24615 DOI |
References
1. McCrery R, Lane F, Benson K, et al. "Treatment of Urinary Urgency Incontinence Using a Rechargeable SNM System: 6-Month Results of the ARTISAN-SNM Study." J Urol. 2020;203(1):185-192. doi:10.1097/JU.0000000000000458
2. ClinicalTrials.gov. "Axonics SacRal NeuromodulaTIon System for Urinary Urgency Incontinence TreatmeNt (ARTISAN-SNM)." Identifier NCT03327948. clinicaltrials.gov
3. U.S. Food and Drug Administration. "Summary of Safety and Effectiveness Data: Axonics Sacral Neuromodulation System, PMA P180046." Approved November 13, 2019. accessdata.fda.gov
4. Benson K, McCrery R, Taylor C, et al. "One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence." Neurourol Urodyn. 2020;39(5):1482-1488. doi:10.1002/nau.24376
5. Pezzella A, McCrery R, Lane F, et al. "Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system." Neurourol Urodyn. 2021;40(2):714-721. doi:10.1002/nau.24615
6. Geynisman-Tan J, Mueller MG, Kenton KS. "Satisfaction with a rechargeable sacral neuromodulation system-A secondary analysis of the ARTISAN-SNM study." Neurourol Urodyn. 2021;40(1):549-554. doi:10.1002/nau.24596