Endocrine Abstracts

Objectives: Sirolimus is an immunosuppressive drug with anti-fibrotic and anti- proliferative activities. Recently, sirolimus (given off-label as a second-line treatment) was found to be associated with a better outcome of Graves’ orbitopathy (GO) at 24 weeks compared to methylprednisolone. Here we conducted a retrospective study to investigate the efficacy and safety of sirolimus compared with methylprednisolone over a longer period of time.

Methods: Data from 40 consecutive patients with moderate-to-severe and active GO [10 men and 30 women, age: 56.6 (13.4) yr.], 20 of whom treated with sirolimus (2 mg orally on first day, followed by 0.5 mg/day for 12 weeks) and 20 with methylprednisolone [500 mg iv/weekly (6 weeks), 250 mg/weekly (6 weeks)], were collected. Primary outcome: overall outcome (composite evaluation) of GO at 48 weeks. Secondary outcomes: overall GO outcome at 24 weeks; at 24 and 48 weeks: 1) outcome of single eye features; 2) outcome of quality of life (GO-QoL); 3) mean change in proptosis; 4) TSH-receptor antibodies (TRAbs); and 5) GO relapse at 48 weeks; 6) adverse events.

Results: The overall GO outcome at 48 weeks did not differ between the two groups, in spite of a trend to a greater proportion of responders in sirolimus group (70% vs 55%). At 24 weeks, the prevalence of responders was greater in sirolimus group (70% vs 35%; P = 0.03). A reduction ≥2 points in clinical activity score (CAS) was more frequent in sirolimus patients both at 24 (80% vs 40%; P = 0.01) and 48 weeks (75% vs 60%; P = 0.03). The proportion of GO-QoL responders (appearance subscale) at 24 weeks was greater in sirolimus group (62.5% vs 26.3%; P = 0.03). No difference was observed for the remaining outcome measures. We registered 6 mild adverse events (AE) (4 patients) at 24 weeks and 8 (7 patients) at 48 weeks in the sirolimus group vs 20 mild AE (15 patients) at 24 weeks and 8 (6 patients) at 48 weeks in methylprednisolone group, none requiring discontinuation of the treatment.

Conclusions: Treatment with sirolimus is followed by a greater overall response of GO and CAS compared with methylprednisolone at 24 weeks, with a similar trend at 48 weeks. A more prolonged period of treatment with sirolimus may be required for a better outcome to be observed over a longer period of time. Our data, together with the safety of sirolimus, confirm sirolimus as a possible alternative treatment for moderate-to-severe and active GO.