Pilot Study of IL-1 Antagonist Anakinra for Treatment of Endometriosis

Renee T Sullender,1 Ravi K Agarwal,2 Marni B Jacobs,1 Jocelyn M Wessels,3 Warren G Foster,3 Sanjay K Agarwal1 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Diego, La Jolla, CA, USA; 2University of California at San Diego School of Medicine, La Jolla, CA, USA; 3Afynia Laboratories Inc, Hamilton, ON, CanadaCorrespondence: Sanjay K Agarwal, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Diego, 9500 Gilman Drive #0633, La Jolla, CA, 92093, USA, Tel +1 858 534-8977, Fax +1 858 534-8856, Email [email protected]: To evaluate the impact of an interleukin-1 (IL-1) antagonist anakinra (Kineret®) on endometriosis-related quality of life (QoL), pain, and inflammatory biomarkers.Methods: This was a single-site, randomized, double-blinded, placebo-controlled, cross-over pilot clinical study of patients recruited at an academic specialty clinic. Eligible participants were females aged 18– 45 years with menstrual cycles every 24– 32 days. Subjects had moderate to severe dysmenorrhea and either a surgical diagnosis of endometriosis or an endometrioma on imaging. Subjects were randomly assigned in a double-blind fashion to receive either the study drug or placebo administered as daily injections during the first 3 periods and then the alternate intervention for the next 3 periods.Results: Fifteen subjects completed the 6 menstrual cycle study. After each period, they completed the Endometriosis Health Profile-30 (EHP-30) QoL questionnaire and an assessment of dysmenorrhea using a 0– 100 Visual Analogue Scale (VAS). All domains of the EHP-30 showed a trend towards improvement, with significant improvements in powerlessness (54.5 vs 63.3, p = 0.04) and self-image (58.1 vs 66.7, p = 0.03) on the study drug compared to placebo. The mean dysmenorrhea VAS also trended toward improvement with a score of 37.5 during active treatment and 42.6 with placebo (p = 0.26). No difference in menstrual cycle length was detected (29.3 days vs 27.7 days, p = 0.56). There were significant differences in multiple inflammatory biomarkers between the study drug and placebo, including BDNF, IL-1, and IL-6 among certain groups.Conclusion: With all EHP-30 domains and the dysmenorrhea VAS showing either a statistical improvement or trend towards improvement, there is justification for a larger study. As no impact on menstrual cycles was detected, anakinra may be a particularly impactful option for women desiring fertility. Additional evaluation is needed on the role of anakinra on inflammatory markers given significant reductions were identified in multiple biomarkers.Plain Language Summary: Endometriosis is a common gynecologic disease afflicting millions of patients. Anakinra is an IL-1 antagonist currently used for treatment of rheumatoid arthritis which has been found to improve quality of life measures for patients with endometriosis. Anakinra also reduces levels of biomarkers known to be associated with endometriosis-related inflammation. More study is needed on the role of anakinra in improving endometriosis symptoms.Keywords: endometriosis, IL-1 antagonist, anakinra, Kineret, pelvic pain, quality of life, inflammation