Clinical outcomes of second-line Treatments cycling in refractory wet OAB patients before switching to intradetrusor injections of onabotulinumtoxin/A: a real world observational study

Introduction: Persistence and adherence rates assessed for various drugs for Overactive Bladder (OAB) in real-world settings are dramatically poor, with almost 70% to 90% of patients discontinuing treatment within 1 year. We investigated the clinical outcomes of second-line treatments in a group of patients with wet-OAB, who then switched to Onabotulinumtoxin A (Onabot/A) intradetrusorial injections. Patients’ discontinuation to treatment and the reasons why patients stopped their oral medications were also investigated. Comparisons with the clinical outcomes and satisfaction to treatment obtained with Onabot/A intradetrusor injections in the same patients were also assessed. Patients and Methods: The outpatient visits charts of 125 wet OAB patients treated with secondline oral agents, who then switched to Onabotulinum toxin A intradetrusor injections, were retrospectively reviewed. We assessed the number and types (immediate or long-acting formulations) of anticholinergics (ACHs) cycled, the use of Mirabegron oral therapy, and persistence to these pharmacological agents since the beginning of treatment until patients switched to Onabot/A intradetrusor injections. Patients were classified as having tried 1, 2, or ≥3 anticholinergics, alone or in combination with Mirabegron, or Mirabegron oral treatment alone. Daily frequency of Urinary Incontinence (UI), as recorded by the 3-day voiding diary and satisfaction to treatment, as scored by a Visual Analog Scale (VAS), both obtained at the last evaluation before being included in the neurotoxin treatment regimen, were retrospectively analyzed. Any eventual side effect due to ACHs and/or Mirabegron treatment was also noted. Daily frequency of urinary incontinence episodes and satisfaction to treatment, as well as rates of discontinuation and side effects, has been investigated in the same patients following Onabot/A intravesical treatment. Results: From January 2000 to October 2015, 125 patients affected by refractory wet OAB have been treated with ACHs and Mirabegron. Twenty-six (31%) patients assumed 2 ACHs and then Mirabegron, 21 (25%) patients cycled 3 ACHs and then Mirabegron, 13 (15%) patients cycled 4 ACHs and then Mirabegron, 15 (18%) cycled 5 ACHs and 9 (11%) patients cycled 6 ACHs. Types of ACHs used were propiverine, trospium, solifenacine, fesoterodine, oxybutynin IR and ER. Fortyone patients, more recently evaluated for their wet-OAB, have been treated only with 1 ACH before switching to Onabot/A intradetrusor injections. Overall duration of treatment increased according to the number of ACHs cycled. The median/IRQ frequency of UI episodes/day and the median (IRQ) VAS score were similarly poor across all the subgroups of patients, regardless of the number of ACHs cycled. Poor efficacy of treatment was reported by 52 (41.6%) of patients, intolerable side effects by 38 (30.4%) patients, and poor efficacy with unpleasant adverse effects in 35 (28%). After discontinuing second-line treatments the 125 patients switched to a third-line therapy represented by Onabot/A intradetrusor injections, 100 U diluted in 10 ml normal saline. Fifty-four patients received from 1 to 4 repeat injections, 36 from 5 to 9 repeat treatments and 16 patients received ≥ 10 repeat injections. For eACH sub-group of patients with different No. of injections, the median/ IQR frequency of daily UI episodes as well as satisfaction to treatment, appeared to be significantly improved as compared to those obtained with ACHs and Mirabegron, as evaluated at the last follow up visit. Improvements remained constant regardless of the number of repeat injections and of the length of follow up, in the majority of cases. Conclusion: The majority of patients affected by wet OAB cycled at least 2 antimuscarinics before switching to a third line-therapy, with a consistent group cycling 5 and 6 different anticholinergic drugs. After switching to Onabot/A intradetrusor injections, the same patients found a prompt improvement in daily UI episodes and satisfaction to treatment. Thus, there is the urgent need to identify pharmacological agents with a better efficacy and safety profile in order to improve adherence and persistence to OAB second-line therapies.