Will teprotumumab supplant traditional options in the treatment of thyroid eye disease?
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Teprotumumab marks beginning of new era
Teprotumumab has marked the dawn of a new era in the treatment of thyroid eye disease.
Finally, this disease is being recognized for the chronic immunological condition that it is, and I anticipate that, much like with rheumatoid arthritis, teprotumumab and other disease-modifying drugs currently in the pipeline are going to change the way this condition is treated. On the other hand, I don’t think that teprotumumab will completely supplant our surgical interventions, either now or even in the future. Again, this is analogous to rheumatoid arthritis.
With the advent of disease-modifying drugs in rheumatoid arthritis, the incidence of hand surgery has greatly decreased. A little more than 30 years ago when I was a medical student, it was common to see patients with gross deformity of their hands from rheumatoid arthritis. Now, we rarely see that type of involvement, and I would suggest that we owe this to the advent of disease-modifying antirheumatic drugs. However, I think that we will always partner disease-modifying drugs with surgery to optimize the care and outcome of the patient.
While most of the manifestations of thyroid eye disease are reversed by teprotumumab, there are some exceptions. For instance, in the majority of my patients, eyelid retraction secondary to thyroid eye disease is not completely reversed by teprotumumab. Whether or not other biological agents will modify those specific features, it is still unknown. In addition, disease manifestations recur in some patients once they stop teprotumumab, and they may need maintenance treatment. We are still trying to iron out what the risk factors are for those patients who are going to need ongoing treatment and which patients are going to respond and stay stable after one course of teprotumumab. However, teprotumumab has paved the way toward more research and many new discoveries, and I am convinced that there will be a lot more treatments available for thyroid eye disease in the near future.
Louise A. Mawn, MD, is a professor of ophthalmology and neurological surgery at Vanderbilt University Medical Center.
Side effects and cost cannot be ignored
First, I would like to acknowledge that teprotumumab has fundamentally altered our approach to the treatment of thyroid eye disease.
However, I do believe that it should be used judiciously and that it is only the beginning of a more targeted approach to the disease.
Judicious use implies considering risk-benefit ratios and cost-effective medicine. I continue to use teprotumumab in active moderate to severe disease, but I do not believe that the risk-benefit ratio justifies its use in mild active disease. As we know, these patients often improve without treatment or with minimal medical intervention, such as selenium or artificial tears. The risk for significant side effects, including hearing loss and fatigue, outweigh the potential small benefits in the treatment of mild disease.
The cost of treatment with teprotumumab cannot be ignored. If less expensive treatments exist that have not been proven to be inferior, these treatments should be considered. The gold standard, EUGOGO IV methylprednisolone protocol, has yet to be compared with teprotumumab in a prospective randomized trial.
The use of teprotumumab in the treatment of chronic disease is intriguing. However, orbital decompression is a durable, less expensive option for proptosis secondary to chronic disease, which, in the right hands, likely has fewer side effects. You could make the argument that the recovery time away from work adds significant cost; however, unless you are operating on billionaires, there is no way that cost approaches the cost of 24 weeks of teprotumumab.
I think of teprotumumab as a first-generation IGF-1R antagonist. Like many first-generation drugs, it enjoys being the first of its kind, and as time progresses, the side effect profile will be even better defined. Second- and third-generation drugs will have the advantage of learning from the problems encountered by teprotumumab. In addition, other pathways (eg, IL-6) have shown significant promise in the treatment of active thyroid eye disease. Competition between these products will benefit us all.
So, will teprotumumab supplant traditional treatment options? If we, as physicians, act responsibly and in the best interest of our patients and the health care system, the answer is no. The more interesting question may be, “What will supplant teprotumumab in the coming years?” I personally do not think that one drug will be dominant but rather there will be a whole host of biologics targeting different pathways, and we will choose the appropriate drug based on the phenotype (and maybe the genotype) of our patients.
Richard C. Allen, MD, PhD, is a professor of ophthalmology at The University of Texas Dell Medical School.
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