Purpose: To characterize and compare the clinical features, timing, and duration of thyroid eye disease relapse after teprotumumab in patients treated during the active versus stable phases of the disease. Methods: A retrospective case series was conducted of 26 adult patients who experienced a return of thyroid eye disease symptoms after completing teprotumumab therapy between July 2021 and July 2024 at 2 academic centers. Patients were stratified by thyroid eye disease phase at treatment initiation (active vs. stable). Data included clinical history, treatment details, and relapse characteristics. Relapse was defined by worsening of proptosis or extraocular motility deficits after completion of treatment. Statistical comparisons were made using t tests and Fisher’s exact test. Results: Of 26 patients, 20 were treated during the active phase and 6 during the stable phase. Active phase patients relapsed sooner (mean 8.2 vs. 12.3 months) and experienced significantly longer relapse duration (mean 11.1 vs. 4.2 months, p = 0.000035). In the active phase group, relapse was associated with progression of clinical signs beyond pretreatment levels, including 1 case of new-onset optic neuropathy. In contrast, stable phase patients uniformly returned to pretreatment clinical baselines without further progression. Both groups had similar rates of adverse events. Conclusions: Thyroid eye disease relapse after teprotumumab differs by disease phase at initiation. Active phase patients experience earlier, more prolonged, and more severe relapses, suggesting teprotumumab acts as a disease modulator. Stable phase patients exhibit shorter, nonprogressive symptom return, which we would term “rebound”—suggesting a distinct mechanism. These findings underscore the need for phase-specific counseling, monitoring, and further investigation into potentially disparate mechanisms of action of teprotumumab in the acute and stable phases.
Shabto et al. (Fri,) studied this question.