In this study, researchers found the ongoing clinical challenge of treating moderate-to-severe Graves' orbitopathy show some potential benefits from the addition of mycophenolate mofetil to the standard of care, methylprednisolone, no benefit from the addition of radiotherapy to oral steroids. The study has published in The Lancet Diabetes & Endocrinology.

"Based on the results radiotherapy should not be considered as first-line treatment of moderate-to-severe Graves' orbitopathy, while the addition of widely available, low-dose mycophenolate mofetil to the standard treatment regimen of high-dose intravenous glucocorticoids could improve treatment outcome with limited side effects," Robin Peeters.

The first of the two randomized trials showed that the addition of the immunosuppressant mycophenolate mofetil to the current first-line treatment of methylprednisolone for Graves' orbitopathy had improved efficacy over IV methylprednisolone alone at 24 weeks; however, the study failed to meet the primary outcomes of response at 12 weeks and relapse at 24 and 36 weeks.

And in the second study, no benefits from the addition of radiotherapy to oral prednisolone were seen, while there were inconclusive results when azathioprine treatment was added to oral steroids, with some signs of a beneficial effect.

The two studies underscore the need for better treatment options for active moderate-to-severe Graves' orbitopathy, or thyroid eye disease, which occurs in 5% to 10% of people with Graves' disease. But with concerns of cumulative toxic effects, the drugs are typically withdrawn after just 24 weeks, and subsequent recurrence at the time of withdrawal is common, with active disease commonly lasting 1 to 2 years.

And at 24 weeks, 38 of 72 (53%) of patients remaining in the monotherapy group and 53 of 75 (71%) in the combination group had responded to treatment (OR 2.16; P = .02). For the primary outcomes of relapse rates at 24 and 36 weeks, there were no significant differences in the monotherapy and combination groups (P = .72 and P = .61, respectively).

However, significantly more patients in the combination group at week 36 had a sustained response (49 of 73; 67%) compared with the monotherapy group (31 of 68; 46%) (P = .01), the authors note. Rates of mild and moderate (grade 1–2) drug-related adverse events were also similar in the monotherapy (20%) and combination (25%) groups (P = 48).

This study is the to investigate the efficacy and safety of add-on mycophenolate to methylprednisolone for moderate-to-severe Graves' orbitopathy.

"Therefore, in patients with active and severe Graves' orbitopathy and no contraindications for mycophenolate combination therapy with this drug could be considered."

"The conflicting results in some clinical studies and the diversity of pathogenic processes that might play a part in each patient with Graves' orbitopathy mean that a personalized, patient-specific, pathway-targeting treatment is required that is tailored to the stage of disease to improve therapeutic efficacy."