Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report submitted by the manufacturer of teprotumumab (Amgen K.K.) on the additional benefits and cost-effectiveness of teprotumumab in patients with mild and moderate-to-severe active thyroid eye disease (TED). This report summarizes the results of a review and reanalysis conducted by the ATAG. The target population was divided into three groups: (a) mild active TED, (b) moderate-to-severe active TED (CAS < 3), and (c) moderate-to-severe active TED (CAS ≥ 3). The comparator for population (a) was symptomatic treatment, and the comparator for populations (b) and (c) was combination therapy of steroid pulse therapy and radiotherapy. In assessing the additional benefits, the manufacturer conducted a systematic review (SR). For populations (a) and (b), no randomized controlled trials (RCTs) suitable for evaluation were identified in the SR restricted to RCTs, and assessment was considered infeasible. For population (c), no RCT directly comparing teprotumumab with the combination therapy was identified. The manufacturer conducted a matching-adjusted indirect comparison (MAIC) using individual patient data from the TED01RV and OPTIC trials and aggregate data from eight RCTs of steroid pulse therapy, assuming equivalent effectiveness between steroid pulse therapy alone and the combination therapy because no evidence showed improved efficacy by adding radiotherapy to steroid pulse therapy. The MAIC showed a statistically significant reduction in proptosis. Although no statistically significant difference was observed for diplopia response, the direction and magnitude of the point estimates were considered supportive of additional benefit. The results were generally consistent with findings from similar previous studies. Based on these results, the manufacturer concluded that teprotumumab had additional benefits. The ATAG independently conducted an SR and identified two RCTs of the combination therapy; how ever, these trials were small and used higher doses than those recommended in Japanese clinical guidelines, and were therefore not considered appropriate as data sources for evaluation. Because the comparator in the analytical framework was the combination therapy, the ATAG noted concerns about substituting its efficacy with results from RCTs of steroid pulse therapy alone. However, given the limit ed available evidence and the difficulty of conducting alternative reanalyses, the ATAG accepted the manufacturer's indirect comparison results and considered teprotumumab as providing additional bene fits in population (c). Thus, the ATAG examined the analysis provided by the manufacturer as the cost effectiveness analysis was appropriate. In the cost-effectiveness analysis, the manufacturer employed a Markov model comprising six health states defined by combinations of three diplopia states and two proptosis states, with quality-adjusted life year (QALY) as the outcome. The ATAG conducted a reanalysis owing to the several challenges identified in the analysis by the manufacturer. Regarding cost parameters, the manufacturer assumed a body weight of 50 kg for estimating drug costs of teprotumumab and used expert opinion for the management costs of steroid pulse therapy, whereas the ATAG adopted values based on National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) data. The manufacturer assumed a recurrence rate of 0% after teprotumumab based on no observed recurrence at Week 28 in the TED01RV trial, whereas the ATAG adopted a 24% recurrence rate based on Kahaly et al. (2024) and estimated recurrence during 24-48 weeks after treatment using an exponential model. For the combination therapy, the manufacturer assumed a recurrence rate of 30.5%, whereas the ATAG adopted 18.4% based on Kahaly et al. (2018). The reanalysis of the ATAG showed that analysis for populations (a) and (b) was infeasible. For population (c), teprotumumab incurred additional costs of JPY 17,452,568 and yielded an additional 1.87 QA LYs compared with the combination therapy, resulting in an incremental cost-effectiveness ratio (ICER) of JPY 9,355,796 per QALY. In conclusion, the results by the ATAG suggested that the ICER for teprotumumab compared with the combination therapy was likely to belong to the interval between JPY 7.5 and 10 million per QALY from the perspective of public healthcare payer in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2026

URL for published report: https://c2h.niph.go.jp/en/results/C2H2407.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com