Corticosteroid-Resistant and Corticosteroid-Dependent AIED Patients Treated With Anakinra: A Decade of Experience

使用阿那白滞素治疗皮质类固醇耐药和皮质类固醇依赖性自身免疫性内分泌疾病患者:十年经验

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Abstract

OBJECTIVE: Patients with autoimmune inner ear disease (AIED) are particularly vulnerable if they stop responding to corticosteroids or if they are dependent on high-dose corticosteroids to maintain hearing, as they have no therapeutic alternatives. We initially demonstrated the efficacy of anakinra in a small open-label clinical trial in corticosteroid-resistant AIED and are conducting a larger phase 2 placebo-controlled clinical trial. A large number of screened patients were ineligible or refused participation; however, for those we could obtain insurance coverage, we have used anakinra to improve and/or stabilize hearing. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS/INTERVENTION: A total of 49 patients representing three cohorts were treated with anakinra from 2013 to 2023, and hearing results followed over time: cohort A, corticosteroid-resistant AIED patients (n = 28); cohort B, corticosteroid-dependent AIED patients (n = 12); and cohort C, AIED patients who have participated in our anakinra trials with hearing improvement but were unable to maintain hearing off drug (n = 9). OUTCOME MEASURES/RESULTS: The anakinra response rate was 46% for cohort A, 83% for cohort B, and 78% for cohort C. In cohort A, a positive durable response was measured by hearing improvement by PTA: in this cohort of 13 patients, 14 ears improved by an average of 14 dB PTA. If we adopt a more conservative measure of improvement in both the PTA and WRS domains, eight ears in eight patients improved by 22% in WRS in this PTA-responsive cohort. After removing three responders who exhibited a WRS ceiling effect and three patients deemed nonresponders as they improved by WRS only, the overall rate of improvement drops to 32% or 7 of 22 evaluable patients. In cohort B, a positive response was considered to achieve hearing stability, with a concomitant reduction in corticosteroid dose by at least 50%. In cohort C, a positive response was to achieve hearing stability. CONCLUSION: Anakinra seems to be efficacious in some patients with corticosteroid-resistant and corticosteroid-dependent AIED.

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