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Thyroid eye disease improves with first-line steroid-sparing agent
The use of methotrexate as first-line therapy with a limited adjuvant IV methylprednisolone to treat active thyroid eye disease led to significant improvements in disease activity and total steroid load, according to data from a retrospective, single-center, consecutive case series published in Clinical Endocrinology.
“Management of [thyroid eye disease] is challenging, and the optimal treatment regimen has yet to be determined,” Jonathan H. Norris, MBChB, FRCOphth, MSc, consultant oculoplastic and ophthalmic surgeon based at the John Radcliffe Hospital in Oxford, U.K., and colleagues wrote in the study background. “Administration of glucocorticoids in the form of pulsed intravenous methylprednisolone is the first-line recommended treatment ... for patients with moderate to severe active [thyroid eye disease]. ... However, chronic use of [glucocorticoids] is associated with several potential significant adverse effects.”
The researchers conducted a retrospective, consecutive audit review of medical records of 24 patients (mean age, 46.8 years) treated by the Oxford multidisciplinary thyroid eye disease team from March 2013 to August 2016. Typically, patients presenting to the clinic with a VISA (vision, inflammation, strabismus and appearance) inflammatory index score of at least 3 are routinely administered a steroid-sparing agent. Patients with insufficient clinical response, adverse effects or contraindications to methotrexate are administered second- and third-line steroid-sparing agents cyclosporine and azathioprine. Clinicians administer an additional three doses of IV methylprednisolone for 3 weeks for patients with sufficient response but persistent active disease.
All patients in the audit were administered IV methylprednisolone with a mean cumulative dose of 2.72 g; 38% of patients received 1.5 g IV methylprednisolone or less, and two patients required more than 4.5 g. All patients but one received methotrexate orally or subcutaneously as a first-line steroid-sparing agent. One patient was administered azathioprine because of chronic lung disease findings on chest X-ray. Twenty of the 23 patients receiving methotrexate started on a 20-mg weekly oral dose, and four of these patients increased to a 25-mg weekly subcutaneous dose. Four patients received 25-mg weekly subcutaneous doses initially. Patients were administered methotrexate for an average of 13 months, and 11 patients (42%) received a second steroid-sparing agent, typically cyclosporine. Three patients required a third agent, including rituximab (Rituxan; Genentech, Biogen) in two cases and azathioprine in one case.
Mean pretreatment VISA inflammatory index score of 5.5 of 10 improved to a mean score of 2.7 (P < .001) at 6 months and 1.4 (P < .001) at 1 year. Four patients did not adequately improve with high-dose IV methylprednisolone and at least two steroid-sparing agents, and they required orbital decompression because of signs of dysthyroid optic neuropathy. One of these patients was contraindicated to methotrexate because of chronic lung disease, and another had to stop methotrexate after 3 months because of chronic cough.
The researchers reported no long-term adverse effects, but three patients stopped methotrexate due to liver function tests, chronic cough and recurrent cystitis.
“Our results illustrate a substantial reduction in total IV [methylprednisolone] dose required compared to the standard dose recommended by [European Group on Graves’ Orbitopathy], alongside a significant improvement in the clinical activity of the disease,” the researchers wrote. They also noted that with their treatment protocol, patients needed 50% fewer visits for IV therapy.
“We recognize that the natural course of [thyroid eye disease] is improvement over time, and further prospective double-blinded controlled trials with larger sample size are needed to confirm long-term [methotrexate] efficacy and safety in treatment of active moderate to severe [thyroid eye disease],” the researchers wrote. – by Tina DiMarcantonio-Brown
Disclosures: The authors report no relevant financial disclosures.