Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy

Abstract

ImportanceMild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO.ObjectiveTo evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO.Design, Setting, and ParticipantsIn this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks.InterventionsParticipants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks.Main Outcomes and MeasuresThe primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded.ResultsA total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group.Conclusions and RelevanceThe results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort.Trial RegistrationClinicalTrials.gov Identifier: NCT02203682

Thicknesses of the retinal layers in patients with Graves’ disease with or without orbitopathy

“…Casini et al found a signi cant decline in mean central GCL thickness in patients with GO compared with healthy controls [23]. Wang et al compared RNFL and GCC (including the RNFL, ganglion cell layer and inner plexiform layer) between patients with active GO, Dysthyroid optic neuropathy (DON) and healthy controls [24]. In active GO and DON, the blood supply to the super cial layer of the macular area is reduced; the smaller the blood vessel density, the thinner the RNFL and GCC.…”

Literature Commentary

“…In this month's issue of JAMA Ophthalmology, Pan et al (4) explored the efficacy of 50 mg of doxycycline daily in patients with mild TAO in a 5-center randomized, double masked, placebo-controlled trial. Of 100 patients with mild TAO, 50 were randomized to 50 mg of doxycycline a day and 50 to placebo with assessments at 4 and 12 weeks.…”

Oral Doxycycline for Mild Thyroid Eye Disease

“…5 Doxycycline is generally well tolerated, with common adverse effects including mild gastrointestinal symptoms and photosensitivity of skin. Only 1 adverse event, mild gastroesophageal reflux, was recorded in relation to doxycycline use in the clinical trial reported by Pan et al 3 A previous case series led by the same senior author 6 studied doxycycline, 50 mg, daily for 12 weeks in 13 patients with active moderate to severe TED (median Clinical Activity Score…”

“…In this issue of JAMA Ophthalmology , Pan et al reported on the efficacy of oral doxycycline in patients with mild TED–based EUGOGO classification. This is a well-designed randomized, double-masked, placebo-controlled trial conducted across 5 hospitals in different regions of China, with most (54%) recruitment from Zhongshan Ophthalmic Center.…”

“…All but 2 patients from the study drug group completed the trial, and final outcome assessment was performed at week 12. The authors found a significant improvement in the composite indicator in the treatment group (38%) compared with the placebo group (16%). Improvement in the composite indicator was defined as meeting at least 1 of the 4 criteria in the study eye without worsening of any item in either eye; reduction of eyelid aperture by 2 mm or more, reduction of proptosis by 2 mm or more, increase in ocular motility by 8° or more in any duction, or increase on Graves ophthalmology-specific quality-of-life (GO-QOL) scale by 6 points or more.…”