High-Dose Glucocorticoids for the Treatment of Sudden Hearing Loss.

BACKGROUND: Systemic glucocorticoids are commonly used for primary therapy of idiopathic sudden sensorineural hearing loss (ISSNHL). However, the comparative effectiveness and risk profiles of high-dose over lower-dose regimens remain unknown. METHODS: We randomly assigned patients with sudden hearing loss of greater than or equal to 50 dB within 7 days from onset to receive either 5 days of high-dose intravenous prednisolone at 250 mg/d (HD-Pred), 5 days of high-dose oral dexamethasone at 40 mg/d (HD-Dex), or, as a control, 5 days of oral prednisolone (Pred-Control) at 60 mg/d followed by 5 days of tapering doses. The primary outcome was the change in hearing threshold (pure tone average) in the three most affected contiguous frequencies from baseline to day 30. Secondary outcomes included speech understanding, tinnitus, communication competence, quality of life, hypertension, and insulin resistance. RESULTS: A total of 325 patients were randomly assigned. Mean change in 3PTAmost affected hearing threshold from baseline to 30 days was 34.2 dB (95% CI, 28.4 to 40.0) in the HD-Pred group, 41.4 dB (95% CI, 35.6 to 47.2) in the HD-Dex group, and 41.0 dB (95% CI, 35.2 to 46.8) in the Pred-Control group (P=0.09 for analysis of variance). There were more adverse events related to trial medication in the HD-Pred (n=73) and HD-Dex (n=76) groups than in the Pred-Control group (n=46). CONCLUSIONS: Systemic high-dose glucocorticoid therapy was not superior to a lower-dose regimen in patients with ISSNHL, and it was associated with a higher risk of side effects. (Funded by the Federal Ministry of Education and Research [BMBF]; EudraCT number, 2015­002602­36.)

Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study.

OBJECTIVE: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91. SETTING: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices). PATIENTS: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies. INTERVENTIONS: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7. MAIN OUTCOME MEASURES: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. RESULTS: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated. CONCLUSIONS: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.

Treatment Satisfaction During Sublingual Immunotherapy with a Five-Grass Pollen Tablet for Allergic Rhinoconjunctivitis: A Prospective, Non-Interventional Study.

BACKGROUND: Sublingual immunotherapy (SLIT) is a safe/well-tolerated alternative to allergen injection immunotherapy for allergic rhinoconjunctivitis (ARC). Patient adherence is essential and patient-related outcome measures including treatment satisfaction are informative/indicative of adherence. OBJECTIVE: The aim was to assess treatment satisfaction with five-grass pollen tablet SLIT under real-life conditions. METHODS: Treatment satisfaction among adults taking SLIT with a five-grass pollen tablet for grass pollen-related ARC was assessed with QUARTIS, a self-report questionnaire dedicated to the management of patients treated with SLIT for ARC. This 1-year prospective, non-interventional, post-authorization study was conducted in Germany between 2008 and 2010. RESULTS: Of the 327 patients treated with the five-grass pollen tablet, 253 completed the QUARTIS questionnaire before and during (at least one item) treatment and were included in this analysis. Between the baseline and the treatment season, significant improvements were documented in nasal and ocular symptoms, and in the impact of allergy on everyday life. At the end of the first treatment period, patients had an improved opinion of the ease of SLIT intake and a significantly improved perception of SLIT. Compliance, overall satisfaction and motivation to continue SLIT the following year were good. Physicians' assessments showed reduced symptoms and a reduced need for symptomatic medication throughout the study. SLIT was also well tolerated. CONCLUSION: Under real-life conditions, five-grass pollen tablet treatment was associated with a good level of treatment satisfaction, good symptom control, a reduced need for symptomatic medication, and favourable tolerability. These facets impacted favourably on patient functioning, disposition towards this medication, and adherence.