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Smoking Linked to Poor Treatment Response to Teprotumumab in TED

Smoking Linked to Poor Treatment Response to Teprotumumab in TED

March 29, 2023

Smoking is a modifiable risk factor that indicates a worse response to treatment for thyroid eye disease (TED) using teprotumumab, according to recent research.

The University of Kansas conducted a retrospective cohort study where they theorized that patients with TED who smoke may experience reduced efficacy of teprotumumab compared to those who do not smoke. The results confirmed the hypothesis, as data showed that smokers with TED displayed less improvement in diplopia, proptosis, and overall clinical activity score (CAS).

“Aligned with our hypothesis, smokers demonstrated poorer response to teprotumumab treatment with regards to reduction of proptosis,” wrote the investigative team, led by Jason A. Sokol, MD.1

Graves’ hyperthyroidism can lead to thyroid eye disease (TED), which has two classifications: type 1, which affects orbital fat without diplopia, and type 2, which involves diplopia within 20 degrees of fixation with restrictive myopathy. TED's risk factors include genetic predisposition and environmental influences, with smoking consistently associated with the development and progression of the disease, according to Sokol and colleagues.

Thyroid Eye Disease

                                            Thyroid Eye Disease Credit: All About Vision

Analysis Between Smokers & Non-smokers

Teprotumumab is a monoclonal antibody that targets insulin-like growth factor 1 receptors (IGF-1R) and has been proven effective in treating thyroid eye disease (TED) by improving proptosis, clinical activity score (CAS), diplopia, and quality of life when compared to a placebo. However, it's unknown whether teprotumumab is as effective in treating smokers with TED, according to investigators. Therefore, the investigative team conducted a retrospective review of patients with TED who had started or completed teprotumumab therapy at the time of data collection, in a single-center study.

The study reviewed a total of 34 patients with thyroid eye disease (TED) who were scheduled to start teprotumumab. Out of these, 16 patients who started or completed treatment during the study period were initially compared. Eventually, 15 patients were included in the statistical analysis, of which 6 patients (40%) had a history of smoking. All smokers had type 2 TED, and all non-smokers had type 1 TED. However, there was no significant difference observed between smokers and non-smokers in baseline variables such as sex, thyroid stimulating hormone, thyroxine, triiodothyronine, and number of infusions completed.

The study evaluated the effect of teprotumumab treatment on smokers and non-smokers. The primary outcome measured was the change in clinical activity score (CAS). The mean reduction in CAS was 3.7±2 in smokers and 4.9±2.2 in non-smokers. Visual acuity (VA) outcomes showed no significant difference between groups, as all smokers had VA of 20/25 or better after treatment with teprotumumab.

Further analysis of the data revealed that proptosis was reduced in both eyes of smokers compared to non-smokers. The reduction was 1.2±1.2 in the right eye and 1.75±0.5 in the left eye in smokers, whereas in non-smokers it was reduced by 4±1.4 in the right eye and 4.2±1.8 in the left eye. This reduction was statistically significant, as noted by the investigators.

Regarding diplopia, there was no significant difference between smokers and non-smokers after teprotumumab treatment, but initial data showed that diplopia was more common in smokers. Out of the 16 initial patients, 85.7% of smokers (6 out of 7) and 66.6% of non-smokers (6 out of 9) had diplopia prior to treatment. Treatment resolved diplopia in one smoker and one non-smoker, while one smoker without diplopia prior to treatment developed it afterward.

The investigators noted that the lack of stratification based on smoking status (current smoker vs. ever smoker) may have affected the results, as smoking may have a dose-dependent effect on teprotumumab outcomes. Therefore, Sokol and colleagues suggest the need for more extensive research to assess the long-term impact of smoking on the efficacy of teprotumumab.

“Despite these limitations, smoking cessation resources and counseling are crucial for those diagnosed with TED to prevent further disease progression and to prevent development of TED in those with thyroid dysfunction,” they wrote.


O'Dell JM, Mussatto CC, Chu RL, Al-Sabbagh MQ, Timoney PJ, Sokol JA. Effects of Smoking on Outcomes of Thyroid Eye Disease Treated with Teprotumumab: A Retrospective Cohort Study. Kans J Med. 2023;16:62-64. Published 2023 Mar 15. doi:10.17161/kjm.vol16.18940