Teprotumumab Shows Long-Term Efficacy in Thyroid-Associated Ophthalmopathy: Presented at ATA

By Frances Morin

WASHINGTON, DC -- October 10, 2018 -- Teprotumumab, an insulin-like growth factor I receptor (IGF-IR) shows sustained improvement in the symptoms and quality of life measures of thyroid-associated ophthalmopathy extending to 72 weeks, according to a study presented here at the 88th Annual Meeting of the American Thyroid Association (ATA).

“Patients’ proptosis, clinical activity scores, and quality of life scores were markedly improved after treatment with teprotumumab,” said George J. Kahaly, MD, Johannes Gutenberg University Medical Center, Mainz, Germany.

Teprotumumab was shown to improve clinical activity and proptosis at 24 weeks in as many as 69% of patients with thyroid-associated ophthalmopathy, compared with 20% in a placebo group, causing no deterioration in the non-study eye.

Those effects were rapid, with 43% of patients showing significant improvements within 6 weeks of treatment, and the overall improvement increased to 74% by week 24 in the teprotumumab group, compared with 20% in the placebo group.

Patients in the teprotumumab group also reported increasing subjective improvements in diplopia starting at week 6 (P< .04) and increases significantly by week 24 (P< .001).

“We were also impressed by the significant change in subjective diplopia,” said Dr. Kahaly. “Nearly two-thirds of patients showed an improvement of at least 1 grade of their diplopia at 24 weeks.”

At baseline, patients in the study had a duration of disease of approximately 5 months in both groups at the study’s starting point. Their rates of proptosis were also similar (23.1 mm in the placebo group and 23.4 in the teprotumumab group), as were their mean CAS scores (5.2 vs 5.1).

Treatment involved teprotumumab infusions every 3 weeks, for a total of 8 infusions, or placebo.

In providing an update on the patients, Dr. Kahaly reported that at week 28 -- 4 weeks after ending treatment -- 73.8% of patients (31 of 42) continued to have a primary response, defined as a composite of at least 2 mm reduction in proptosis and at least a 2 point reduction in CAS, compared with 13.3% (6 of 45) of controls (P< .001).

In the placebo group, there were a total of 9 orbital surgeries in 5 patients during the off-treatment follow-up, compared with 3 surgeries in 2 patients in the treatment group.

In the longer-term follow up at week 72, representing 48 weeks following the treatment period, 53.3% of patients in the treatment group maintained a response to the treatment.

“The majority of teprotumumab responders maintained response after 1 year off of treatment,” Dr. Kahaly said. “These results suggest no acute rebound of disease following the 24-week treatment, which is usually observed when treating patients with other immunosuppressive treatments.”

Treatment-emergent adverse events (AEs) in the study were described as mostly minor or moderate and transient. The most common AEs in the teprotumumab group were nausea, muscle spasms, diarrhoea, and hyperglycaemia.

“The overall efficacy of teprotumumab was emphasised by the time to first response, which was rapid, and the longer we treated them, the higher the response rate was, and the higher the number of patients without subjective diplopia was,” said Dr. Kahaly.

Funding for this study was provided by River Vision USA and Horizon Pharma.

[Presentation title: 48-Week Follow-Up of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Treatment Trial of Teprotumumab in Thyroid-Associated Ophthalmopathy. Abstract 2]

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