Pilot data indicates efficacy from anakinra against endometriosis

Pilot data indicates efficacy from anakinra against endometriosis | Image Credit: © Alena - © Alena - stock.adobe.com.

The interleukin-1 (IL-1) antagonist anakinra (Kineret; Swedish Orphan Biovitrum) has shown efficacy against endometriosis symptoms, according to a pilot study published in the International Journal of Women’s Health.¹

Endometriosis is reported in 5% to 10% of women, though the condition is likely underdiagnosed. Women with endometriosis experience significant physical and mental health burdens that impact quality of life, but treatment options often provide limited benefit and are temporary in nature. Many options also prevent or contradict pregnancy.

Inflammation has been established as a central mechanism of endometriosis, with the inflammatory response promoting progesterone resistance. This makes IL-1 a potential key inflammatory mediator in patients with endometriosis, but the potential benefits of IL-1 remain unclear.²

Anakinra, an IL-1 antagonist with FDA approval for rheumatoid arthritis treatment, may be effective against endometriosis symptoms.¹ To evaluate these potential benefits, investigators conducted a single-site, randomized trial.

Participants included women aged 18 to 45 years with painful menstrual cycles every 24 to 32 days and menstrual periods of 10 days or less. These participants were recruited from the University of California at San Diego Center for Endometriosis Research and Treatment.

Surgically proven endometriosis or image findings of endometriosis within 5 years before enrollment was available for every participant. The Biberoglu & Behrman (B&B) scale questionaire was used to determine moderate to severe dysmenorrhea.

Women who were pregnant or attempting pregnancy, planned to receive a vaccine during the study, had a contraindication to anakinra, or with a prior hysterectomy or oophorectomy were excluded from the analysis.

Participants were randomly assigned to receive 100 mg anakinra daily for 3 periods followed by placebo daily for 3 periods or placebo daily for 3 periods followed by 100 mg anakinra daily for 3 periods. Both participants and staff were blinded to the randomization until after data was collected.

The study drug was administered during menses through subcutaneous injections. During the first visit, participants’ pelvic pain was assessed using the B&B scale and a visual-analog scale (VAS), while the Endometriosis Health Profile 30 (EHP-30) questionnaire was used to determine quality of life.

Inflammatory markers were measured at the start and end of menstrual cycles through blood samples. An improvement in dysmenorrhea symptoms was reported as the primary outcome of the analysis, determined based on the dysmenorrhea specific portion of the B&B questionnaire.

There were 15 participants included in the final analysis, 7 of whom received anakinra followed by placebo while 8 received placebo followed by anakinra. Demographic characteristics did not significantly differ between groups.

A reduction in mean B&B dysmenorrhea scores was reported during anakinra treatment cycles vs placebo, but this decline was not statistically significant, at 1.4 vs 1.6, respectively. However, an improvement was found for mean dysmenorrhea VAS scores, at 37.5 vs 42.6, respectively.

Improvements were also noted for EHP-30 domains. Powerlessness and self-image domains were significantly improved, at 54.5 and 58.1, respectively, for anakinra treatment vs 63.3 and 66.7, respectively, for placebo.

Shorter periods were observed during anakinra treatment cycles, but this was not statistically significant at 5 days vs 5.3 days from placebo. Similarly, menstrual cycle length had a nonsignificant increase of 29.3 days vs 27.7 days, respectively.

Completed blood draws were reported for 3 participants. In these patients, significantly reduced brain Derived Neurotrophic Factor levels were reported during the anakinra treatment cycles vs placebo cycles. Significant changes were not identified for other biomarkers of endometriosis using Mann–Whitney analyses.

These results indicated potential clinical and physiological benefits from anakinra treatment in patients with endometriosis. Investigators recommended a larger and more comprehensive trial to determine long-term outcomes.

References

1. Sullender RT, Agarwal RK, Jacobs MB, Wessels JM, Foster WG, Agarwal SK. Pilot study of IL-1 antagonist anakinra for treatment of endometriosis. Int J Womens Health. 2024;16:1583-1593. doi:10.2147/IJWH.S467041
2. Kyama CM, Mihalyi A, Simsa P, et al. Non-steroidal targets in the diagnosis and treatment of endometriosis. Curr Med Chem. 2008;15(10):1006–1017. doi:10.2174/092986708784049595