Effects of TNF Blockade on Human BPH/LUTS

Summary

Specific Aim 1. To evaluate the efficacy of TNF antagonist action in BPH/LUTS Specific Aim 2. Define the consequences of TNF antagonist therapy on prostate tissue Specific Aim 3. Identify genetic predictors to stratify patients with differential response to TNF-antagonist therapy.

Timeline

Start

2024-01-24

Primary completion

2028-04-01

Completion

2028-06-01

Publications

• Background Vickman RE, Aaron-Brooks L, Zhang R, Lanman NA, Lapin B, Gil V, Greenberg M, Sasaki T, Cresswell GM, Broman MM, Paez JS, Petkewicz J, Talaty P, Helfand BT, Glaser AP, Wang CH, Franco OE, Ratliff TL, Nastiuk KL, Crawford SE, Hayward SW. TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease. Nat Commun. 2022 Apr 19;13(1):2133. doi: 10.1038/s41467-022-29719-1.
• Background Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol. 2007 May;51(5):1202-16. doi: 10.1016/j.eururo.2006.12.011. Epub 2006 Dec 11.
• Background Glaser AP, Mansfield S, Smith AR, Helfand BT, Lai HH, Sarma A, Yang CC, Taddeo M, Clemens JQ, Cameron AP, Flynn KE, Andreev V, Fraser MO, Erickson BA, Kirkali Z, Griffith JW; LURN Study Group. Impact of Sleep Disturbance, Physical Function, Depression and Anxiety on Male Lower Urinary Tract Symptoms: Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). J Urol. 2022 Jul;208(1):155-163. doi: 10.1097/JU.0000000000002493. Epub 2022 Feb 25.
• Background Liu G, Andreev VP, Helmuth ME, Yang CC, Lai HH, Smith AR, Wiseman JB, Merion RM, Erickson BA, Cella D, Griffith JW, Gore JL, DeLancey JOL, Kirkali Z; LURN Study Group. Symptom Based Clustering of Men in the LURN Observational Cohort Study. J Urol. 2019 Dec;202(6):1230-1239. doi: 10.1097/JU.0000000000000354. Epub 2019 May 23.
• Background Helfand BT, Smith AR, Lai HH, Yang CC, Gore JL, Erickson BA, Kreder KJ, Cameron AP, Weinfurt KP, Griffith JW, Lentz A, Talaty P, Andreev VP, Kirkali Z; LURN. Prevalence and Characteristics of Urinary Incontinence in a Treatment Seeking Male Prospective Cohort: Results from the LURN Study. J Urol. 2018 Aug;200(2):397-404. doi: 10.1016/j.juro.2018.02.075. Epub 2018 Mar 1.
• Background Helfand BT, Glaser AP, Kasraeian A, Sterious S, Talaty P, Alcantara M, Alcantara KM, Higgins A, Ghiraldi E, Elterman D. Men with lower urinary tract symptoms secondary to BPH undergoing Aquablation with very large prostates (> 150 mL). Can J Urol. 2021 Dec;28(6):10884-10888.
• Background Helfand BT, Kasraeian A, Sterious S, Glaser AP, Talaty P, Alcantara M, Alcantara KM, Higgins A, Ghiraldi E, Elterman DS. How I do it: Aquablation in very large prostates (> 150 mL). Can J Urol. 2022 Apr;29(2):11111-11115.
• Background McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, Albertsen P, Roehrborn CG, Nickel JC, Wang DZ, Taylor AM, Waldstreicher J. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998 Feb 26;338(9):557-63. doi: 10.1056/NEJM199802263380901.
• Background McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.
• Background Roehrborn CG, Bruskewitz R, Nickel JC, McConnell JD, Saltzman B, Gittelman MC, Malek GH, Gottesman JE, Suryawanshi S, Drisko J, Meehan A, Waldstreicher J; Proscar Long-Term Efficacy and Safety Study Group. Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1194-8. doi: 10.1097/01.ju.0000112918.74410.94.
• Background Setia SA, Smith J, Cendo D, Yoder J, Gorin MA, Allaway MJ, Vourganti S. Outcomes of freehand transperineal prostate biopsy with omission of antibiotic prophylaxis. BJU Int. 2022 Jul;130(1):54-61. doi: 10.1111/bju.15590. Epub 2021 Dec 23.
• Background Lightner DJ, Wymer K, Sanchez J, Kavoussi L. Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis. J Urol. 2020 Feb;203(2):351-356. doi: 10.1097/JU.0000000000000509. Epub 2019 Aug 23.
• Background He J, Guo Z, Huang Y, Wang Z, Huang L, Li B, Bai Z, Wang S, Xiang S, Gu C, Pan J. Comparisons of efficacy and complications between transrectal and transperineal prostate biopsy with or without antibiotic prophylaxis. Urol Oncol. 2022 May;40(5):191.e9-191.e14. doi: 10.1016/j.urolonc.2022.01.004. Epub 2022 Feb 12.
• Background Ahmed Ali U, Martin ST, Rao AD, Kiran RP. Impact of preoperative immunosuppressive agents on postoperative outcomes in Crohn's disease. Dis Colon Rectum. 2014 May;57(5):663-74. doi: 10.1097/DCR.0000000000000099.
• Background Quaresma AB, Yamamoto T, Kotze PG. Biologics and surgical outcomes in Crohn's disease: is there a direct relationship? Ther Adv Gastroenterol. 2020 Jul 16;13:1756284820931738. doi: 10.1177/1756284820931738. eCollection 2020.
• Background Hyman NH, Cheifetz AS. PUCCINI: Safety of Anti-TNF in the Perioperative Setting. Gastroenterology. 2022 Jul;163(1):44-46. doi: 10.1053/j.gastro.2022.04.050. Epub 2022 May 4. No abstract available.
• Background Cohen BL, Fleshner P, Kane SV, Herfarth HH, Palekar N, Farraye FA, Leighton JA, Katz JA, Cohen RD, Gerich ME, Cross RK, Higgins PDR, Tinsley A, Glover S, Siegel CA, Bohl JL, Iskandar H, Ji J, Hu L, Sands BE. Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery. Gastroenterology. 2022 Jul;163(1):204-221. doi: 10.1053/j.gastro.2022.03.057. Epub 2022 Apr 10.
• Background Bechara FG, Podda M, Prens EP, Horvath B, Giamarellos-Bourboulis EJ, Alavi A, Szepietowski JC, Kirby J, Geng Z, Jean C, Jemec GBE, Zouboulis CC. Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa: The SHARPS Randomized Clinical Trial. JAMA Surg. 2021 Nov 1;156(11):1001-1009. doi: 10.1001/jamasurg.2021.3655.

Drugs

Indications