Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial

• Published in: The journal of clinical endocrinology and metabolism 2023-09, Vol.108 (10), p.2615-2625
• Main Authors: Taylor, Peter, Rajendram, Rathie, Hanna, Stephanie, Wilson, Victoria, Pell, Julie, Li, Chunhei, Cook, Anne, Gattamaneni, Rao, Plowman, Nicholas, Jackson, Sue, Hills, Robert, French, Robert, Uddin, Jimmy M, Lee, Richard W J, Dayan, Colin M
• Format: Article
• Language: English
• Subjects: Azathioprine; Clinical; Clinical trials; Graves' disease; Patients; Quality of life; Radiation therapy; Surgery
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgad084

Abstract   Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up. Methods Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. Results Data were available at 3 years from 68 of 126 randomized subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a binary clinical composite outcome measure (BCCOM), modified European Group on Graves’ Orbitopathy score, or Ophthalmopathy Index. Clinical Activity Score (CAS), Ophthalmopathy Index, and Total Eye Score improved over 3 years (P < .001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24 of 64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery [odds ratio (OR) 16.8; 95% CI 2.95, 95.0; P = .001]. Higher baseline levels of CAS, Ophthalmopathy Index, and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery. Conclusion In this long-term follow-up from a clinical trial, 3-year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes.