Effects of Anakinra in Subjects With Corticosteroid-resistant/Intolerant Meniere's Disease and Autoimmune Inner Ear Disease

Inclusion Criteria:

• meet diagnostic criteria for Autoimmune Inner Ear Disease (AIED) with activedeterioration in one ear as defined below

• SNHL of greater than 30dB at one or more frequencies in the active ear. Thecontralateral ear may have any hearing threshold that is either stable or worsening,but may not exhibit improvement in response to corticosteroids even if the moreactive ear declines. Active deterioration is defined as a 15dB decline at onefrequency (excluding 250 or 8kHz as a sole indicator) on their audiogram, or 10dB at 2+ frequencies developing in > or equal 3 days but < or equal 90 days, or if thehearing loss evolved in less than 3 days, the patient displayed features suggestiveof an autoimmune disorder

• Capable of understanding and giving informed consent

• Have 2 sequential audiograms following the decline in hearing >or equal 28 daysapart with no demonstrable improvement in hearing following corticosteroid therapy (<or equal 5dB of improvement at any individual frequency (250, 500, 1000, 2000 and 4000Hz) and <12% improvement in WRS)

• Patients must have been treated with oral or IT prednisone with no demonstrableimprovement or attempted to be treated and deemed intolerant. Steroid intolerance isdefined as unable or unwilling to take corticosteroids because of a prior untowardeffect or a current medical condition that would negatively be impacted by steroiduse

• Must have completed steroid therapy, including any intratympanic steroid therapy

• Meniere's disease defined according to the AAO criteria, with the additionalrequirement of corticosteroid resistance AND no new diuretics may be instituted ordose increased from 28 days prior to trial enrollment

• Patients must be fluent in English as all word recognition scores are based ontesting in English

• Patients may have other autoimmune disease(s) Females of childbearing potential,must be practicing a method of birth control considered effective and medicallyacceptable by the investigator for a minimum of 2 months prior to the study and atleast 2 months after last administration of study drug

• Males similarly must be practicing a method of birth control considered effectiveand medically acceptable by the investigator for a minimum of 2 months prior to thestudy and at least 2 months after last administration of study drug

Exclusion Criteria:

• Evidence of retrocochlear pathology (vestibular schwannoma) or inner earmalformation (Mondini Malformation or Enlarged Vestibular Aqueduct) based on imaging

• Prior treatment with gentamicin for Meniere's Disease

• Most recent decline in hearing occurring >90 days prior to trial enrollment

• Positive test for Muckle-Wells mutation

• Concurrently receiving methotrexate, TNF-antagonist therapy or any otherimmunosuppressive therapy

• Steroid-dependent hearing loss

• Any immunodeficiency syndrome

• Active or chronic infections

• Currently receiving, or having received treatment for a malignancy in the past 3years

• Chronic renal insufficiency (a creatinine clearance of <49mL/min) or chronic renalfailure

• Neutropenia prior to treatment with anakinra

• Receipt of live vaccine <3 months prior to enrollment

• Previous treatment with an IL-1 antagonist for any clinical indication

• First-degree relative with a diagnosis of a CAPS disease

• History of active narcotic abuts, including prescription narcotics

• Pregnant or lactating females

• Non-English speaking patients

• Seropositive for Hepatitis B, C, HIV or tuberculosis on screening, with theexception of presence of antibodies to Hepatitis B in subjects reporting priorvaccination, and presence of positive skin testing for TB in subjects who receivedBCG in the past

• History of suicidal ideation, significant depression that resulted inhospitalization, or answers "yes" during C-SSR screening

• Prior participation in any type of clinical trial using a medication that inhibitsinterleukin-1 activity

• Known hypersensitivity to E.coli derived products