Re: Safety, Tolerability, and Efficacy of LiRIS 400 mg in Women with Interstitial Cystitis/Bladder Pain Syndrome with or without Hunner Lesions
Journal of Urology
Editorial Comment: The lidocaine-releasing intravesical system (LiRIS) is a passive, nonresorbable intravesical system inserted cystoscopically and designed to provide continuous, controlled release of lidocaine into the bladder over a 2-week period, after which it is removed. There was a positive anticipation that this treatment system might provide symptomatic relief for at least a segment of patients with interstitial cystitis/bladder pain syndrome (IC/BPS), based on the logic of the rationale and from results in 2 small studies, 1 of which was presented at the American Urological Association annual meeting in 2016,1 showing positive results in patients with Hunner lesions (HL). This article reports the results from 2 phase 2 studies conducted to assess efficacy and safety of this device in patients with IC with and without HL. Daily average pain score change from baseline using the numeric rating scale (NRS) was the primary end point. The secondary end point for patients with HL was a change in the number of lesions assessed by cystoscopy. Other study end points included average daily worst pain, micturition episode frequency and urgency episode frequency. Interestingly, exclusions consisted of a pain catastrophizing scale score of over 38 at screening, as well as other factors. The study design was interesting. In study 1, there were 2 consecutive 14-day treatments: LiRIS-LiRIS, placebo (filled device)-LiRIS and placebo-placebo. In study 2, the patient received either LiRIS or placebo for a continuous 14-day period. In study 1, 59 patients were randomized and received treatment. A total of 11 patients discontinued the study. In study 2, 131 patients were randomized and received treatment. A total of 21 patients discontinued in both studies. The primary time point was week 4 for after removal of treatment, day 28 in study 1 and day 14 in study 2. For study 1, there were numerical but not statistically significant trends in favor of the lidocaine group, with a drop in the NRS pain score from 5.5e2.6 and 6.0e2.8, and 5.6e4.1 in the placebo group. In study 2, there was no significant difference in the reduction of HL between the 2 groups; the same was true of the patients who had HL in study 1. In both studies, lidocaine was measurable “in the majority of patients” in urine and plasma for at least 14 days following insertion of the device. Urinary concentrations were 1,600 to 3,000 times plasma concentrations. Patient-reported outcomes in study 1 were inconclusive with large variability in a small sample size. In study 2, there was an improvement for both groups but no statistical difference in study 1, with 19.4% of patients reporting dysuria, 16.1% urinary tract infection, hematuria and bladder discomfort 12.9% each, and bladder pain 9.7%. The authors’ conclusion was, “The results of the studies did not demonstrate a significant treatment effect for LiRIS 400 mg compared with placebo for treatment of IC/ BPS with or without HL.” Looking at mean baseline scores vs least squares mean change for various parameters, and calculating percent change for the drug-drug vs placebo-placebo group in study 1, there certainly are numerical differences for all but 1 important parameter: daily average pain score, at 49% decrease vs 27%, daily worst pain score 40% vs 22%, micturition frequency 23% vs 15%, but urgency episodes per day 49% vs 53%. The placebo response is not as high as I would have expected compared to drug effect for anything except urgency episodes. None of the patient-reported outcomes was specifically reported except to say that there was no change. It could be that the dose of drug was not high enough (it is unclear what would constitute a dangerous plasma concentration) or the intravesical contact was not long enough. The intellectual property surrounding continuous delivery intravesically certainly seems worthy of exploration for other problems such as overactive bladder in women, and I suspect that somewhere this is already in the works. So could this well-reported study be considered a “successful failure” from some standpoints?
Evans R, Kohan A, Moldwin R, Radecki D, Geib T, Peters KM. Re: safety, tolerability, and efficacy of LiRIS 400 mg in women with interstitial cystitis/bladder pain syndrome with or without Hunner lesions. J Urol. 2022 Jan;208(1):233-234.