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Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

ABSTRACT: Thyroid eye disease (TED; also known as thyroid-associated ophthalmopathy) is an autoimmune condition with disabling and disfiguring consequences. Teprotumumab is the first and only medication approved by the United States Food and Drug Administration for the treatment of TED. We review the efficacy and safety of teprotumumab in TED, highlighting results from the 2 randomized, double-masked, placebo-controlled trials. Post-approval case reports of teprotumumab use in patients with compressive optic neuropathy (CON) and inactive TED were similarly favorable to those from the trials. The preliminarily results of teprotumumab for CON and inactive TED should be investigated in formal clinical trials. Teprotumumab should be avoided in pregnancy. Evidence also suggests that teprotumumab may exacerbate pre-existing inflammatory bowel disease, worsen hyperglycemia, and be associated with hearing impairment. Patients at risk for these adverse events need to be closely monitored with baseline and periodic assessments.

SUBMITTER: Teo HM

PROVIDER: S-EPMC8630371 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

Teo Honeylen Maryl HM Smith Terry J TJ Joseph Shannon S SS

Therapeutics and clinical risk management 20211125

Thyroid eye disease (TED; also known as thyroid-associated ophthalmopathy) is an autoimmune condition with disabling and disfiguring consequences. Teprotumumab is the first and only medication approved by the United States Food and Drug Administration for the treatment of TED. We review the efficacy and safety of teprotumumab in TED, highlighting results from the 2 randomized, double-masked, placebo-controlled trials. Post-approval case reports of teprotumumab use in patients with compressive op ...[more]

PMID: 34858025

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Project description:BackgroundTeprotumumab significantly improved proptosis and diplopia in patients with active, moderate-to-severe thyroid eye disease (TED) in previous North American and European studies. This is the first evaluation of efficacy and safety of teprotumumab for active, moderate-to-severe TED in Japanese patients.MethodsThis randomised, double-masked, placebo-controlled trial was conducted in 16 centres in Japan. Main inclusion criteria were as follows: age 20-80 years; Graves' disease, in a euthyroid or mild hypo/hyperthyroid state; clinical activity score (CAS) ≥3; moderate-to-severe TED; ≥3-mm increase in proptosis before TED onset and/or proptosis ≥18 mm at baseline; and TED duration ≤9 months. Patients were randomised (1:1, stratified by smoking status) to either teprotumumab or placebo. Patients received eight intravenous infusions, one every three weeks for 24 weeks. Patients, investigators, site personnel (except formulating pharmacists) were masked. Primary endpoint was proptosis responder rate (percentage of patients with ≥2-mm proptosis reduction from baseline) at week 24 in the intent-to-treat population. Adverse events were assessed in all patients. This trial was registered at Japan Registry for Clinical Trials (jRCT2031210453).FindingsFifty-four patients were randomised (teprotumumab, 27; placebo, 27) between February and November 2022. All patients completed the randomised period, although one teprotumumab patient and two placebo patients missed ≥2 doses. At week 24, the proportion of patients with proptosis response was higher in the teprotumumab group (89%, 24/27) compared with the placebo group (11%, 3/27), 95% confidence interval, 61-95; P<0.0001. Study drug-related adverse events (AEs) occurred in 14 patients (52%) in the teprotumumab group and two patients (7%) in the placebo group; hyperglycaemia-related events were reported in six (22%) and one patient (4%), and hearing impairment in four (15%) and one (4%) patient, respectively. Study drug-related serious AEs and deaths were not reported.InterpretationTeprotumumab significantly improved proptosis compared with placebo in Japanese patients with active TED. No study drug-related serious AEs were observed.FundingHorizon Therapeutics plc (now Amgen).

Project description:PurposeIn recent trials, 50% of patients treated with teprotumumab for thyroid eye disease had significant improvements in proptosis at 6 weeks. However, a small subgroup of patients did not have a significant response by week 12. We examine the outcomes at week 24 in patients from both trials who had little or no proptosis response at week 12.DesignIn this post hoc analysis, data from teprotumumab-treated patients in the placebo-controlled randomized phases 2 and 3 trials were reviewed.MethodsPatients treated with teprotumumab or placebo with a ≤2 mm reduction from baseline in proptosis at week 12 and completed assessments at both the weeks 12 and 24 visits were included. The main outcome measures were a change in proptosis, clinical activity score (CAS) and diplopia in response to teprotumumab therapy at baseline and weeks 6, 12, 18, and 24.ResultsFrom the phases 2 and 3 studies, 24 patients from the treated and placebo groups were included for analysis (48 total). In the teprotumumab group, of the 24 who had no improvement in proptosis (≥2 mm from baseline) at 12 weeks, 15 (63%) demonstrated a clinically significant improvement at week 24. No patients from the 24 placebo patients had a clinically significant improvement in proptosis at 12 weeks, and 24 weeks. At week 12, 22 patients (92%) in the teprotumumab group had a significant reduction in the CAS (≥2 points) and at 24 weeks all patients achieved this reduction. At week 12, 11 (46%) patients from the placebo group had a significant improvement, while 10 (42%) had a significant improvement at 24 weeks. 22 of the 24 patients (92%) in the teprotumumab group had a diplopia grade > 0 at baseline. At week 12, 12 of the 22 (55%) had improvement in diplopia ≥ 1 grade. By week 24, 16 patients (73%) had an improvement in diplopia ≥ 1 grade. In the placebo group, 15 (63%) had significant diplopia. At week 12, 3 (20%) from this group had improvement in diplopia ≥ 1 grade, while at 24 weeks this number rose to 4 (27%).ConclusionsThere is variability in the time taken to manifest a clinically significant response to teprotumumab, some patients my need a longer time to respond.

Dataset Information

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

Publications

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

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