Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab

Abstract

Purpose: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. Methods: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. Results: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (–2.9 mm in active and –2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS (P < 0.01) and reduction in ocular motility restriction (P < 0.01) were maintained during interruption. Conclusions: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

Teprotumumab: A Review in Thyroid Eye Disease

“…Currently available real-world data on the use of teprotumumab in the treatment of TED are limited, but several studies including ≥ 10 patients [ 20 – 29 ] suggest that teprotumumab may be effective in a more diverse disease population than that included in clinical trials. For example, in observational cohort studies of patients with heterogeneous TED ( n = 74 [ 20 ] and 21 [ 21 ]), teprotumumab was associated with proptosis response rates of 71–73%, significantly improving outcomes such as proptosis (change in mm; p < 0.01 vs baseline) regardless of TED activity [ 20 , 21 ] or severity [ 21 ].…”

“…Currently available real-world data on the use of teprotumumab in the treatment of TED are limited, but several studies including ≥ 10 patients [ 20 – 29 ] suggest that teprotumumab may be effective in a more diverse disease population than that included in clinical trials. For example, in observational cohort studies of patients with heterogeneous TED ( n = 74 [ 20 ] and 21 [ 21 ]), teprotumumab was associated with proptosis response rates of 71–73%, significantly improving outcomes such as proptosis (change in mm; p < 0.01 vs baseline) regardless of TED activity [ 20 , 21 ] or severity [ 21 ]. A retrospective study specifically in chronic (> 2 years), stable TED showed that teprotumumab was associated with a 90% proptosis response rate, as well as significant improvements in proptosis (mm), CAS and diplopia (all p < 0.05 vs baseline; n = 31), and EOM volume and orbital fat volume (both p < 0.01; n = 15) [ 22 ].…”

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease

“…Across all studies, data on 88 patients who were treated with teprotumumab either beyond disease duration of 9 months and/or with a CAS <4 were identified (Table 1) [11 ▪ ,12–14,15 ▪▪ ,16,18,19 ▪ ]. Some authors sought to report specifically on outcomes in patients with longer duration of disease and/or those with low CAS scores at the time of treatment initiation, while others included patients with both high and low CAS scores and reported outcomes separately for the two groups; in such instances, we included their data only from the low CAS cohorts.…”

“…In the literature included here, participants with low CAS or longer duration TED were intended to be treated with teprotumumab according to the same protocol as described in the phase 2 and phase 3 clinical trials. Specifically, teprotumumab was administered every 3 weeks for eight total doses, with the initial dose being 10 mg/kg and subsequent doses at 20 mg/kg; in one study [12], participants received a variable number of doses because of drug supply interruption, while in a second study, one participant had received only six of eight planned infusions at the time of publication [16]. As noted below, in the largest study reported, participants must have received at least three doses to be included [15 ▪▪ ].…”

“…Although initial clinical practice was to treat TED patients with disease characteristics similar to those of participants in these trials, physicians quickly expanded their use of teprotumumab to include patients with longer duration of disease, TED manifestations other than proptosis, and lower CAS scores. Case reports [7,8 ▪ ,9] and case series [7,10,11 ▪ ,12–14,15 ▪▪ ,16] suggested that medical therapy in TED patients with longstanding diplopia and/or proptosis, as well as patients with compressive optic neuropathy (who were not included in the clinical trials), could benefit from teprotumumab treatment and experience improvements in their TED that was comparable to outcomes seen with drug treatment in the clinical trials.…”