JU INSIGHT Longitudinal Fluctuations in Treatment Response for Refractory Urgency Incontinence

By: Whitney K. Hendrickson, MD, University of Utah School of Medicine, Salt Lake City; Chong Zhang, MS, University of Utah School of Medicine, Salt Lake City; J. Eric Jelovsek, MD, MMEd, MSDS, Duke University, Durham, North Carolina; Ingrid E. Nygaard, MD, MS, University of Utah School of Medicine, Salt Lake City; Angela P. Presson, PhD, MS, University of Utah School of Medicine, Salt Lake City | Posted on: 19 Jan 2024

Hendrickson WK, Zhang C, Jelovsek JE, Nygaard IE, Presson AP. Longitudinal fluctuations in treatment response after onabotulinumToxinA and sacral neuromodulation for refractory urgency incontinence. J Urol. 2024;211(1):134-143.

Study Need and Importance

Urgency incontinence (UUI) symptoms fluctuate over time. Current analytic approaches, while crucial to understanding treatment efficacy for UUI, do not estimate transitions between treatment success and failure. Markov models have been used to quantify treatment response in diseases whose symptoms fluctuate over time. Using a Markov model to describe symptom fluctuations may help patients and clinicians chose a therapy with improved expectations.

What We Found

Over 6 months, the transition from success to failure occurred in 36% of women after onabotulinumtoxinA (BTX) and 43% after sacral neuromodulation (SNM). There was a 38% and 18% probability over 30 days that women returned to objective and subjective success after failure, respectively (Table). The 30-day transition probability from success to failure was 25% and 30% lower for BTX than SNM for objective and subjective response, respectively (Table). Those receiving BTX had a reduced hazard of transition from subjective success to failure vs SNM. Otherwise, there were no significant differences in hazard of transition from objective success to failure and failure to success between treatments.

Table. Treatment Response Transition Probabilities per 30 Days Over 6 Months

		BTX Probability (95% CI)	SNM Probability (95% CI)	BTX/SNM ratio Probability (95% CI)	P value
Objective treatment response
From	To
Success	Failure	0.10 (0.08, 0.13)	0.14 (0.12, 0.17)	0.75 (0.55, 0.95)	.013
Failure	Success	0.40 (0.30, 0.49)	0.36 (0.28, 0.44)	1.11 (0.73, 1.50)	.60
Censored at additional therapy
Failure	Success	0.37 (0.27, 0.47)	0.39 (0.30, 0.47)	0.98 (0.62, 1.34)	.9
Subjective treatment response after 40 d
From	To
Success	Failure	0.14 (0.11, 0.17)	0.21 (0.16, 0.25)	0.70 (0.51, 0.89)	.002
Failure	Success	0.18 (0.13, 0.24)	0.17 (0.11, 0.22)	1.14 (0.65, 1.64)	.6
Censored at additional therapy
Failure	Success	0.18 (0.13, 0.23)	0.18 (0.12, 0.23)	1.04 (0.58, 1.50)	.9
Abbreviations: BTX, onabotulinumtoxinA; SNM, sacral neuromodulation. Subjective treatment response was modeled using a piecewise transition rate with a change point at 40 days from treatment. Therefore, results are modeled before and after 40 days.

Limitations

We compared 200 units of BTX to SNM, therefore these results may not be applicable to 100 units of BTX. We evaluated outcomes to 6 months; thus, results may differ long term. We did not account for reprogramming of SNM; thus, some failure to success transitions may be due to reprogramming.

Interpretation for Patient Care

Many women fluctuate in and out of failure, but over 30 days nearly 20% to 40% return back to success. There may be some incremental benefit of 200 units BTX over SNM within the first 6 months of therapy, as those receiving BTX are less likely to transition from objective or subjective success to failure and have a slower transition to subjective failure. Future trials comparing treatment efficacy for UUI, should consider including a Markov model to describe symptom fluctuations.