title: Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss.
abstract: OBJECTIVE
  To evaluate the effect of transtympanic administration of tumor necrosis factor alpha (TNF-alpha) blockers to patients suffering from autoimmune inner ear disease (AIED).
  
  
  METHODS
  Nonrandomized, prospective pilot study.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  9 patients (4 men and 5 women; aged 51.22 +/- 13.11 years) presenting with autoimmune sensorineural hearing loss who responded to oral steroid treatment. Two groups of patients were treated. Group A consisted of 5 patients with AIED who could not be tapered off steroids. Group B consisted of 4 patients who were treated with intratympanic anti-TNF-alpha antibody therapy alone after a relapse of hearing loss following discontinuation of steroids.
  
  
  METHODS
  A Silverstein MicroWick local delivery system was placed in the round window niche and the patients were treated for 4 weeks with a weekly infusion of infliximab, a monoclonal antibody against TNF-alpha.
  
  
  METHODS
  Evaluation of hearing thresholds at 250-8000 Hz was performed before and after implantation of the Silverstein MicroWick and local delivery of the TNF-alpha blocker.
  
  
  RESULTS
  Local administration of the TNF-alpha blocker allowed methylprednisolone to be tapered off without loss of hearing function in 4/5 steroid-dependent patients. Four additional patients were treated only with anti-TNF-alpha perfusion to the round window membrane without concomitant systemic administration of methylprednisolone. In 3 of these 4 patients, the pure tone average improved to 22.6 +/- 15.7 dB, resulting in hearing recovery comparable to treatment with systemic methylprednisolone. The 7 responding patients showed a significant reduction of recurrence of hearing loss to 0.028 +/- 0.072 episodes per month over the 4.3 +/- 2.4 months of the post-treatment period compared to 0.84 +/- 0.4 recurrences per week seen in the pretreatment period.
  
  
  CONCLUSIONS
  The results of this pilot trial demonstrate that in patients with AIED, transtympanic delivery of the TNF-alpha blocker infliximab once weekly for 4 weeks allowed steroids to be tapered off, resulted in hearing improvement and reduced disease relapses. These preliminary efficacy and safety results appear encouraging enough to warrant further follow-up and studies for better determination of the potential clinical utility of local administration of infliximab for autoimmune hearing loss.
authors.affiliation: Department of Otorhinolaryngology, University of Liège, Liège, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Van Wijk
authors.forename: H
authors.initials: H
authors.lastname: Staecker
authors.forename: E
authors.initials: E
authors.lastname: Keithley
authors.forename: P P
authors.initials: PP
authors.lastname: Lefebvre
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000187:drug effects*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy*; D006801:Humans; D000069285:Infliximab; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012405:Round Window, Ear / Q000378:metabolism; D055502:Secondary Prevention; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014432:Tympanic Membrane / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008775:Methylprednisolone