TNF-alpha Inhibitor Therapy Suppresses Growth of the Prostate Gland
Ra'ad Al-Faouri, MD MMSc, Christina Sharkey, MS, Leo Tsai, MD PHD MSc, Zongwei Wang, PHD, Aria F. Olumi, MD.
Beth Israel Deaconess Medical Center, Boston, MA, USA.
BACKGROUND: Previous studies have established a relationship between prostate inflammation and the development of BPH. Steroid 5 alpha reductase type 2 (SRD5A2) is a pivotal enzyme in the development and growth of the prostate gland and the critical target for BPH therapy. We previously demonstrated that tumor necrosis factor alpha (TNF-a) regulates the epigenetic change of SRD5A2, leading to suppression of SRD5A2 gene and protein expression. However, little is known whether TNF-a inhibitor therapy affects prostatic growth. Here we aimed to evaluate the effect of TNF-a inhibitor therapy on the growth rate of prostate through analyzing the data of serial pelvic imaging scans.METHODS: In this retrospective cohort study, electronic records at Beth Israel Deaconess Medical Center were searched for men aged 18 and over who had serial pelvic Images (MRI or CT scans) while receiving TNF-a inhibitors. 99 men were included in the treatment cohort after applying exclusion criteria (TNF-a treatment duration < 1 year, any pelvic/prostate surgery/radiation, use of 5ARIs, advanced prostate cancer, androgen deprivation therapy, testosterone therapy, poor image quality, or imaging interval <1 year). An age-matched cohort was constructed with the same inclusion/exclusion criteria but absent TNF-a therapy (n=99). The total prostate volume (TPV) was measured and calculated from baseline and follow-up imaging. Clinical data was collected for all men.
RESULTS: There were no significant differences between the two groups in age, demographics, BMI or comorbidities. Mean baseline TPV was similar in the TNF- a inhibitor therapy group and control group (27.52±8.9 cc vs 27.3±9.6 cc, p-value: 0.71). For the entire cohort, the average imaging follow up duration was 3.79±0.32 years with no significant difference between the treatment and control groups. The median growth rate for men in the treatment cohort was significantly lower than those in the control group (-0.01 cc/year IQR= 1.2 compared to 0.68 cc/year IQR= 2.8, P-value 0.001). In a multiple regression model adjusting for age, race, initial TPV and BMI, men in the treatment group still had a significantly lower growth rate compared to the control group (-0.03 cc/year IQR: 0.82 vs 0.67 cc/year IQR: 0.93, p-value: 0.001).CONCLUSIONS: TNF-a inhibitors are negatively correlated with prostatic growth. Men with autoimmune diseases who are treated with TNF-a inhibitors may experience fewer urinary symptoms related to prostatic enlargement. Our study suggests that inflammatory mediators regulate prostatic growth.
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