title: Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease.
abstract: BACKGROUND
  Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals.
  
  
  METHODS
  We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (≤10%) and an acceptable (≥30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period.
  
  
  RESULTS
  Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1β plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1β plasma levels.
  
  
  CONCLUSIONS
  We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01267994.
  
  
  BACKGROUND
  NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vambutas
authors.forename: Martin
authors.initials: M
authors.lastname: Lesser
authors.forename: Virginia
authors.initials: V
authors.lastname: Mullooly
authors.forename: Shresh
authors.initials: S
authors.lastname: Pathak
authors.forename: Gerald
authors.initials: G
authors.lastname: Zahtz
authors.forename: Lisa
authors.initials: L
authors.lastname: Rosen
authors.forename: Elliot
authors.initials: E
authors.lastname: Goldofsky
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy*; D006801:Humans; D057194:Intention to Treat Analysis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D007759:Labyrinth Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000305:Adrenal Cortex Hormones; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta