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Androgen Deprivation Therapy Increases Risk for Rheumatoid Arthritis
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Treatment with androgen deprivation therapy appeared to increase risk for rheumatoid arthritis among older men with localized prostate cancer, according to study results.
“Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with rheumatoid arthritis in this large cohort of elderly men with prostate cancer,” David D. Yang, MD, and colleagues wrote.
Yang — a medical student in the department of radiation oncology at Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School at the time the study was conducted and now a resident in internal medicine at Beth Israel Deaconess Medical Center — used the SEER-Medicare linked database to evaluate the association between ADT and rheumatoid arthritis among men with prostate cancer.
Investigators analyzed data from 105,303 men aged 66 years and older diagnosed with localized prostate cancer from 1992 to 2006.
Less than half (43%) of men received ADT. After 5 years, men who received ADT appeared significantly more likely than those who did not receive ADT to develop rheumatoid arthritis (5.4% vs. 4.4%; P < .001).
Receipt of any ADT appeared associated with a 23% increased risk for rheumatoid arthritis (HR = 1.23; 95% CI, 1.09-1.4).
Risk for rheumatoid arthritis increased as ADT duration increased. Men treated with ADT for 1 month to 6 months demonstrated a 19% increased risk; those treated with ADT for 7 months to 12 months demonstrated a 29% elevated risk; and men who underwent ADT for 13 months or longer demonstrated a 33% increased risk.
Healio Rheumatology spoke with Yang about the study, the potential explanation for the association between ADT and rheumatoid arthritis, and how clinicians should counsel their patients about the benefits and risks of ADT.
Question: What prompted this research?
Answer: We were curious to see if ADT, which lowers testosterone levels, would be associated with a higher incidence for autoimmune disease. We chose one of the most common autoimmune diseases among older adults to study — rheumatoid arthritis.
Q: How did you conduct the study?
A: We identified approximately 100,000 patients with prostate cancer from the SEER-Medicare database. These patients had received a prostate cancer diagnosis between 1992 and 2006 and more than 40% of the patient population received ADT as a treatment method. Using statistical methods, we were then able to see whether the use of ADT was associated with a greater likelihood for developing rheumatoid arthritis.
Q: What did you find?
A: We found two main things. First, we found that the receipt of any ADT was associated with a nearly one-fourth increased risk for a subsequent diagnosis of rheumatoid arthritis. Second, we found that a longer duration of treatment with ADT was associated with a higher likelihood for being diagnosed with rheumatoid arthritis.
Q: What are the potential explanations for this association?
A: Androgens have immunosuppressive properties. Our thought is that, by suppressing the effects of androgens, ADT is somehow causing increased activation of the immune system and thereby leading to autoimmune conditions, such as rheumatoid arthritis. The exact molecular mechanisms behind how androgens are immunosuppressive are an active topic of investigation.
Q: How should clinicians counsel their patients about the potential benefits and risks of ADT?
A: Clinicians and patients should be aware that rheumatoid arthritis may be a potential side effect of ADT, particularly when anticipating a long course of treatment with ADT. We know from clinical trials that ADT decreases the risk for death by nearly half among men with high-risk localized and locally advanced prostate cancer. So, in this case, the benefit of ADT clearly outweighs the potential risks. However, among patients with intermediate-risk disease, clinicians and patients should carefully consider the pros and cons of ADT before making an informed treatment decision. – by Jennifer Southall
Reference:
Yang DD, et al. Ann Oncol. 2018;doi: 10.1093/annonc/mdx744.
For more information:
David D. Yang , MD, can be reached at Dana-Farber/Brigham and Women’s Cancer Center, 75 Francis St., Boston, MA 02115; email: ddyang@partners.org.
Disclosure: Yang reports no relevant financial disclosures.