A pilot study indicates that anakinra, an interleukin-1 (IL-1) receptor antagonist, may offer a novel approach to managing endometriosis-related pain and inflammation without disrupting fertility. The randomized, double-blind, placebo-controlled, cross-over trial at the University of California at San Diego (UCSD) evaluated anakinra's impact on pelvic pain and quality of life in women with endometriosis. While the reduction in dysmenorrhea pain scores was not statistically significant, the study highlighted improvements in quality of life and a significant decrease in the inflammatory marker brain-derived neurotrophic factor (BDNF). These findings suggest anakinra could be a potential non-hormonal therapeutic option for endometriosis, a condition affecting 5-10% of reproductive-aged women.
Study Design and Methods
The study, sponsored by Swedish Orphan Biovitrum (SOBI), enrolled women aged 18–45 with regular painful menstrual cycles and surgically proven endometriosis or imaging findings of endometrioma. Participants were randomized to receive either 100 mg of anakinra daily or a placebo during menses for three periods, followed by a cross-over to the other treatment for an additional three periods. Pain was assessed using the Biberoglu & Behrman (B&B) scale and a visual-analog scale (VAS), while quality of life was measured using the Endometriosis Health Profile 30 (EHP-30) questionnaire. Blood samples were collected to analyze inflammatory markers, including interleukins, MCP, TNF-α, BDNF, CA-125, and CRP.
Key Findings
Mean B&B dysmenorrhea scores decreased, though not statistically significantly, in anakinra treatment cycles compared to placebo (1.4 vs 1.6, p = 0.40). Similarly, mean dysmenorrhea VAS scores trended toward improvement with anakinra (37.5 vs 42.6, p = 0.26). Notably, the EHP-30 showed statistically significant improvements in the powerlessness (54.5 vs 63.3, p = 0.04) and self-image (58.1 vs 66.7, p = 0.03) sub-scales during anakinra treatment. Importantly, menstrual cycle length remained consistent, suggesting that ovulation was not impaired.
Biomarker Analysis
Analysis of inflammatory markers revealed that BDNF levels were significantly lower during anakinra treatment (p = 0.0001). Specifically, BDNF levels for Treatment Group A were significantly lower during active treatment in Cycles 1–3 than placebo during Cycles 4–6 (p = 0.0001). BDNF levels for Treatment Group B were also significantly lower during active treatment in Cycles 4–6 than during placebo in Cycles 1–3 (p = 0.0350). Significant reductions were also observed in IL-1RA and IL-6 levels in certain treatment groups.
Implications and Future Directions
These findings suggest that anakinra may offer a novel, non-hormonal approach to managing endometriosis-related pain and inflammation. The preservation of menstrual cycles is a significant advantage, as current FDA-approved medications often preclude pregnancy. Further studies are warranted to assess anakinra's long-term efficacy, impact on fertility rates, and potential to modify the disease process. According to Dr. Sanjay Agarwal, the corresponding author, "Given the positive clinical trends and decrease in inflammatory biomarkers, further study for the treatment of endometriosis with anakinra could be beneficial for the many patients suffering from this disease."
Limitations
The study's limitations include a small sample size and participant drop-out, partly due to the COVID-19 pandemic. These factors may have limited the statistical power to detect significant differences in some outcomes. A larger, multi-center study is needed to confirm these findings and further evaluate the potential of anakinra as a therapeutic option for endometriosis.
