Comparison of Methimazole/Hydrocortisone Ointment with Oral Methimazole in Patients with Graves Disease: A Prospective, Randomized, Open-Label, Parallel-Group, 18-Month Study

摘要

Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT).Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD).Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen.Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completedthe 18-month treatment period. Compared with the MMI group (n = 76), the CATO-treated group (n = 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12-150] vs 22 [7-60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%} person-time; P < 0.001), and a higher remission rate (year 1: 46/69 [66.7%] vs 65/72 [90.3%] patients, P = 0.001; year 2: 40/69 [58.0%] vs 60/72 [83.3%] patients, P = 0.001; year 3: 34/69 [49.3%] vs 57/72 [79-2%] patients, P < 0.001; and year 4: 30/69 [43-5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reportedin the CATO group.Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients.