Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss.
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.
Van Wijk
F
F
Department of Otorhinolaryngology, University of Liège, Liège, Belgium.
Staecker
H
H
Keithley
E
E
Lefebvre
P P
PP
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
D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008775:Methylprednisolone