ABSTRACT: Immune-mediated inner ear disease (IMED) is a cause of rapidly progressive auditory dysfunction. Patients are often responsive to high-dose corticosteroids and the disease is believed to be mediated by an antibody to inner ear proteins. To date, no therapies have proven effective as corticosteroid-sparing agents. Rituximab is a monoclonal antibody that depletes B cells, resulting in a reduction in autoantibody production. For that reason, rituximab was evaluated in a small pilot study in patients with IMED to see if there was a signal suggesting benefit. In all, 5/7 patients met the primary endpoint of an improvement in pure tone average (500-3000 Hz) by 10 dB in at least one ear, or an improvement in word identification score by at least 12% at 24 weeks, both relative to screening precorticosteroid values after 1 course of treatment. No significant adverse events were reported. The results of this study suggest further evaluation of rituximab as a treatment for IMED is indicated.
Audiology and Neurotology 10/2010; 16(4):214-21. · 2.46 Impact Factor
ABSTRACT: 1. To correlate exostosis severity with ear canal evaporative cooling. 2. To assess hearing and complications after canalplasty.
Retrospective chart review.
A retrospective chart review from 1990 to 2007 at a university tertiary referral center.
Surfers from the west coast of the United States were twice as likely to have severe exostoses in the right ear compared with the left. Evaporative cooling from a predominant northerly wind direction during the coldest water temperature months in this region may contribute to this lateral bias because surfers on this coast spend most of their time facing west. Few postoperative complications were identified. No cases of facial nerve injury or entry into the temporomandibular joint occurred. Differences in preoperative versus postoperative pure-tone hearing thresholds were not significant.
Exostosis severity seems to correspond to the ear that is more exposed to the predominant coastal wind. We propose that evaporative cooling in a cold water environment contributes to greater progression of exostoses in the ear with more exposure to the predominant wind. Exostosis removal using the postauricular approach carries a low complication rate.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 10/2009; 31(2):345-51. · 1.44 Impact Factor
ABSTRACT: To report the adverse effects associated with prolonged high-dose prednisone for the treatment of autoimmune inner ear disease (AIED).
Prospective data collected as part of a multicenter, randomized, controlled trial for the treatment of corticosteroid-responsive AIED with methotrexate.
Tertiary referral centers.
One hundred sixteen patients with rapidly progressive, bilateral sensorineural hearing loss.
All patients completed a 1-month course of prednisone (60 mg/d). In Phase 2, 67 patients with improvement in hearing underwent a monitored 18-week prednisone taper, resulting in 22 weeks of prednisone therapy at an average dose of 30 mg per day. Thirty-three patients were randomized to receive methotrexate in Phase 2. Thirty-four patients received prednisone and placebo.
Adverse events (AE) in patients treated with prednisone only.
Of 116 patients, 7 had to stop prednisone therapy during the 1-month challenge phase due to AE. Of 34 patients, 5 were unable to complete the full 22-week course of prednisone due to AE. The most common AE was hyperglycemia, which occurred in 17.6% of patients participating in Phase 2. Weight gain was also common, with a mean increase in body mass index of 1.6 kg/m2 (95% confidence interval, 0.77-2.3) during the 22-week steroid course. Patients entering Phase 2 were followed for a mean of 66 weeks. No fractures or osteonecrosis were reported.
Although high-dose corticosteroids are associated with known serious side effects, prospective data in the literature are limited. The present study suggests that with appropriate patient selection, monitoring, and patient education, high-dose corticosteroids are a safe and effective treatment of AIED.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 05/2009; 30(4):443-8. · 1.44 Impact Factor
ABSTRACT: Autoimmune Inner Ear Disease (AIED) is an idiopathic progressive, often bilateral, sensironeural hearing loss that occurs over weeks to months, generally resulting in significant auditory disability. Response to treatment with immunomodulators other than corticosteroids has been poor. Data from a guinea pig model of AIED and a recent open label trial of etanercept suggested potential treatment benefit. Based on these preliminary results, we conducted a pilot placebo controlled trial of etanercept in AIED patients.
Twenty AIED patients were enrolled in a 12-week blinded placebo (PLA) controlled randomized clinical trial of etanercept (ETA) with 25 mg SC twice weekly. Patients received treatment for 8 weeks with a 4-week follow-up off-treatment. The primary study endpoint was an improvement in pure tone threshold (PTA) of 10 Db in two consecutive frequencies and/or improvement in speech discrimination of >12% at week 8.
Patient demographics were similar for the ETA and PLA patients. Seventeen subjects (8 ETA, 9 PLA) completed the trial. The 3 dropouts were due to lack of efficacy. One ETA and 2 PLA subjects achieved the primary endpoint (p > 0.999). One ETA and 1 PLA pt demonstrated improved in hearing loss and vertigo severity by VAS and hearing disability. No safety issues were observed.
The results of this pilot trial demonstrate that etanercept 25 mg twice weekly for 8 weeks was no better than placebo for treatment of AIED in this patient population.
Ontology & Neurotology 10/2005; 26(5):903-7. · 1.90 Impact Factor