Local Perfusion of the Tumor Necrosis Factor α Blocker Infliximab to the Inner Ear Improves Autoimmune Neurosensory Hearing Loss

Abstract

Objective: To evaluate the effect of transtympanic administration of tumor necrosis factor α (TNF-α) blockers to patients suffering from autoimmune inner ear disease (AIED). Study Design: Nonrandomized, prospective pilot study. Setting: Tertiary referral center. Patients: 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-α antibody therapy alone after a relapse of hearing loss following discontinuation of steroids. Intervention: A Silverstein MicroWick^TM 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-α. Main Outcome Measure(s): Evaluation of hearing thresholds at 250–8000 Hz was performed before and after implantation of the Silverstein MicroWick and local delivery of the TNF-α blocker. Results: Local administration of the TNF-α 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-α 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-α 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.