Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators

Abstract

Background: Thyroid eye disease (TED) is a visionthreatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. Methods: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/ or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. Results: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of .4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. Conclusions: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

Thyroid dermopathy responds to teprotumumab therapy

“…Hyperglycemia was reported in 10% of patients, regardless of if they were diabetics or not. However, these values were controlled with medication and diet adjustment and levels returned to baseline after completion of teprotumumab in all patients ( 11 ). Hearing impairment was also reported in five patients, which all resolved ( 4 ).…”

“…Clinical trials have demonstrated that patients tolerate teprotumumab well ( 11 ). Most adverse effects (AEs) were transient and resolved while patients continued in their study group ( 4 , 5 ).…”

“…Most adverse effects (AEs) were transient and resolved while patients continued in their study group ( 4 , 5 ). The most common side effects reported are muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (12%), fatigue (12%), hyperglycemia, and hearing impairment (10%) ( 11 ). Serious AEs were uncommon in both trials ( 11 ).…”

“…The most common side effects reported are muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (12%), fatigue (12%), hyperglycemia, and hearing impairment (10%) ( 11 ). Serious AEs were uncommon in both trials ( 11 ). Due to the increased risk of diarrhea, special attention is to be placed on patients with inflammatory bowel disease due to the increased risk of exacerbation.…”

Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management

“…[ 124 ] It is administered via an intravenous route and is contraindicated in patients with inflammatory bowel disease or poorly controlled diabetes, pregnant or nursing patients, prepubertal children, and those on concomitant biologics. [ 125 ] In addition, recent data have highlighted the potential risk of other adverse events, including hearing loss[ 126 127 128 129 ] and cognitive decline[ 130 ] as well as recurrence of TED symptoms in a subset of teprotumumab-responsive patients[ 124 ] [see Fig. 4 ].…”