LBA01-08 EFFICACY OF TARGETED MAST CELL INHIBITION THERAPY IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

Abstract

You have accessJournal of UrologyCME1 Apr 2023LBA01-08 EFFICACY OF TARGETED MAST CELL INHIBITION THERAPY IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME Praveen Thumbikat, Goutham Pattabiraman, Catherine Osborn, Stephen Murphy, and Anthony Schaeffer Praveen ThumbikatPraveen Thumbikat More articles by this author , Goutham PattabiramanGoutham Pattabiraman More articles by this author , Catherine OsbornCatherine Osborn More articles by this author , Stephen MurphyStephen Murphy More articles by this author , and Anthony SchaefferAnthony Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003360.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a component of urologic chronic pelvic pain syndrome (UCPPS) and affects men, leading to chronic pain in the pelvic region or genitalia that is often accompanied by increased urinary frequency and urgency as well as sexual dysfunction. CPPS has an estimated prevalence rate of 6-12% of the male population with most diagnoses between the ages of 35-45. We have previously demonstrated that mast cells can be critical mediators of both chronic pelvic pain and lower urinary tract symptoms (LUTS). In this pilot clinical study, we therefore sought to identify subtypes of CP/CPPS characterized by mast cell dysfunction and evaluate the therapeutic efficacy of functional mast cell targeting on mast cell tryptase levels as well as on symptoms of pain and voiding dysfunction. METHODS: Men with CP/CPPS were recruited and evaluated in an open label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the NIH-CPSI and AUA-SI. Isolated cells from post-prostatic massage urine were evaluated for immune changes using mRNA expression analysis. RESULTS: 31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-weeks, active tryptase concentrations were significantly reduced from 49.03±14.05 ug/ml to 25.49±5.48 ug/ml (p<0.05). The NIH-CPSI total score was reduced with a mean difference of 5.2±1 along with reduction in the pain, urinary and quality of life sub scores (p<0.001). A reduction in the AUA-SI was observed following treatment (p<0.05). NanoString mRNA analysis of isolated cells revealed downregulation of immune related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed. CONCLUSIONS: This pilot study presents a method to identify CP/CPPS patients with mast cell dysfunction and target them for therapeutic intervention using a novel, safe combination therapeutic approach. The resulting subgroup of CP/CPPS patients were shown to have a therapeutic response as measured primarily by a reduction in mast cell tryptase, a potential surrogate biomarker and reduction in CP/CPPS symptoms. These pilot studies will form the basis for future randomized placebo-controlled studies to evaluate these agents as CP/CPPS therapies. Source of Funding: This work was supported by the National Institute of Diabetes and Digestive and Kidney (NIDDK) grant R01DK083609 to Praveen Thumbikat. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this abstract © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1179 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Praveen Thumbikat More articles by this author Goutham Pattabiraman More articles by this author Catherine Osborn More articles by this author Stephen Murphy More articles by this author Anthony Schaeffer More articles by this author Expand All Advertisement PDF downloadLoading ...