Pilot Study of the IL-1 Antagonist Anakinra for the Treatment of Endometriosis Related Symptoms
Keywords
Abstract
Description
Endometriosis is a chronic inflammatory disease1 that affects 5 -10% of reproductive aged women1,2. It is characterized by the presence of uterine endometrium outside the uterus. The condition causes health distress through pelvic pain and decreased QOL. Current therapies to temporarily control symptoms include surgery as well as medical options that prevent pregnancy and have significant side-effects.3,4 The most common symptoms with endometriosis include dysmenorrhea, dyspareunia and NMPP. Ultimately these lead to a decrease in QOL. All current medical therapies to treat endometriosis pain prevent or contradict pregnancy.
Inflammation is a well-established central figure in the pathophysiology of endometriosis(1). Increasingly, data is suggesting that IL-1 is a mediator of inflammation in endometriosis (2, 3). In addition, there are data that single nucleotide polymorphisms at the IL-1A gene locus are associated with endometriosis risk (4). Hence, it is rational to assess anakinra, an IL-1 antagonist, in the control of symptoms and inflammation due to endometriosis. Therefore, we propose this pilot study testing an FDA approved medication (anakinra) to reduce IL-1 and on dysmenorrhea due to endometriosis without stopping periods (a sign of ovulation).
Anakinra is a self-administered subcutaneous injectable medication that is FDA approved for the treatment of rheumatoid arthritis. As an IL-1 antagonist, it works by decreasing inflammation and is administered daily by the patient. Because Anakinra interferes with the immune system functioning, the major concern with the use of Anakinra is reduced resistance to infection. Others include injection site reactions such as redness, itching, rash, and pain. Bruising or bleeding also can occur, but it is rare. These effects usually stop after one - two weeks. Headaches and low white blood cell counts can also occur, but these are very rare. Anakinra should be used with caution in those with chronic kidney disease.
Anakinra is not specifically FDA approved for endometriosis. Although no data on its use in women with endometriosis have been published, there is no reason to expect women with endometriosis would be at any particular or increased risk than those in the general population.
This study is a randomized, double blinded, placebo controlled, cross-over clinical pilot study of 20 women. Patients diagnosed with laparoscopically proven endometriosis within the last 5 years will be randomized to either treatment with an FDA approved medication (Anakinra) or a placebo. This is an investigator initiated single center study sponsored by the Swedish Orphan Biovitrum (SOBI). SOBI will provide the study drug and placebo.
Dates
| Last Verified: | 03/31/2020 |
| First Submitted: | 05/26/2019 |
| Estimated Enrollment Submitted: | 06/16/2019 |
| First Posted: | 06/18/2019 |
| Last Update Submitted: | 04/02/2020 |
| Last Update Posted: | 04/06/2020 |
| Actual Study Start Date: | 03/31/2020 |
| Estimated Primary Completion Date: | 12/31/2021 |
| Estimated Study Completion Date: | 12/31/2021 |
Condition or disease
Intervention/treatment
Drug: Active Treatment with Anakinra
Drug: Standard Comparison
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Active Treatment with Anakinra 10 subjects will be enrolled in this group. Initial treatment will consist of 100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day. | Drug: Active Treatment with Anakinra The study drug is100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection. |
| Placebo Comparator: Standard Comparison 10 subjects will be enrolled in this group. This group will be given placebo injections as their initial treatment. The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection. These individuals will self-administer the placebo each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day. | Drug: Standard Comparison The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | Female |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Women aged 18-40 with regular menstrual periods every 24-32 days and not lasting more than 6 days per month - Laparoscopically proven endometriosis. - At least a moderate level of menstrual pain based on the patient reported parameters of the B&B pain scale (>4/9) with dysmenorrhea being scored at least 2/3. - Willing to remain on your current method of hormone therapy for duration of study Exclusion Criteria: - History of hysterectomy or oophorectomy. - Non-response to GnRH agonist/antagonist, DMPA, aromatase inhibitors or danazol. - Currently pregnant or attempting pregnancy. - Contraindication to anakinra. - Chronic kidney disease stage 4 and 5 or creatinine clearance <30mL/min/1.73m2. - Abnormal LFTs, CBC or serum electrolytes including estimated GFR. - Patient refusal. - Plan to receive a live vaccine |
Outcome
Primary Outcome Measures
1. Comparison of the impact of anakinra versus placebo on menstrual pain (dysmenorrhea) using the modified Biberoglu and Behrman scale. [Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.]
Secondary Outcome Measures
1. Comparison of the impact of anakinra versus placebo on dyspareunia and non menstrual pelvic pain using the modified Biberoglu and Behrman scale. [Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.]
2. Comparison of the impact of anakinra versus placebo on the quality of life using the Endometriosis Health Profile 30 questionnaire (EHP-30), conducted after each course of study medication administration. [Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.]
3. Comparison of serum inflammatory markers before and after anakinra administration. [There will be blood tests at the start and end of each of of the subject's next 6 menstrual periods for a total of 12 blood draws.]
