Nancy A Melville

October 23, 2017

VICTORIA, British Columbia — The addition of nonsteroidal intravenous (IV) mycophenolate to the recommended therapy of IV methylprednisolone significantly improves severe Graves' orbitopathy, with benefits in clinical as well as quality-of-life measures in a randomized trial.

"We found that in patients with active and moderate to severe Graves' orbitopathy, the add-on of a moderate daily dose of mycophenolate to an established moderate single and cumulative dose of methylprednisolone was safe, well-tolerated, and led to significant improvements in quality of life as well as ophthalmic symptoms and signs," said senior author George J Kahaly, MD, PhD, professor of medicine and chief, endocrine outpatient clinic, at the Gutenberg University Medical Center, Mainz, Germany.

Dr Kahaly presented the findings here at the 2017 Annual Meeting of the American Thyroid Association.

Although IV methylprednisolone is recommended in guidelines as first-line treatment for active and severe Graves' orbitopathy, response is not always reliable and patients frequently relapse after discontinuation.

Meanwhile, mycophenolate is seen as a potentially beneficial nonsteroidal immunosuppressive agent — it inhibits T-lymphocytes as well as B-lymphocytes to mitogenic and allospecific stimulation, providing anti-inflammatory mechanisms.

The study suggests a potentially important new strategy given the clinical challenges in the treatment of Graves' orbitopathy, said Angela M Leung, MD, assistant professor of medicine, division of endocrinology, diabetes, and metabolism, University of California, Los Angeles David Geffen School of Medicine.

"The current traditional recommendations for the management of Graves' orbitopathy are not universally successful; thus, the potential promise of mycophenolate combined with IV methylprednisolone as an additional treatment option is exciting," she told Medscape Medical News.

Consider Add-On Mycophenolate in Absence of Contraindications

To evaluate the effects of mycophenolate as add-on therapy to methylprednisolone, Dr Kahaly and colleagues with the European Group on Graves' Orbitopathy (EUGOGO), conducted a randomized, observer-blinded study of 164 patients with Graves' orbitopathy euthyroid for at least 2 months.

Patients were randomized to IV methylprednisolone alone for 12 weeks (0.5 g/week for 6 weeks, followed by 0.25 g/week for 6 weeks), with an additional 24 weeks of follow-up, or the same protocol plus 0.720-g oral mycophenolate sodium/day for 24 weeks.

Response was defined as reduction of at least two parameters of a composite ophthalmic index without simultaneous deterioration in any parameter.

At 24 weeks, the response rate in the methylprednisolone-alone group was 53%, vs 71% in the combination group (odds ratio [OR], 2.16; P = .026).

The combination group also showed significant improvements in measures of overall ophthalmic improvement, clinical activity and severity scores, downgaze duction, eyelid and caruncle swelling, and quality of life.

There were also significant improvements in serum levels of thyroid stimulating hormone receptor autoantibodies in the combination group, which Dr Leung remarked was interesting.

At 36 weeks, further improvements were seen in nine (14%) patients in the methylprednisolone-alone group and 13 (20%) in the combination group, while three patients relapsed in each group (8.6% and 5.8%, respectively).

Overall improvement at 36 weeks was observed in 52.3% of methylprednisolone-alone and 74.2% of combination therapy patients (P = .02).

There were no significant differences in mild-to-moderate side effects between the methylprednisolone-alone and combination groups (20% vs 25%, respectively; P = .47).

"Because there is a clear advantage of combination treatment in response rate, in the absence of contraindications to mycophenolate, patients with active and severe Graves' orbitopathy may be considered for combination therapy," said Dr Kahaly.

The study was funded in part by Novartis. Dr Leung had no relevant financial relationships.

2017 Annual Meeting of the American Thyroid Association. October 19, 2017; Victoria, British Columbia. Abstract 4.

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