Long-term outcome of graves

Simone Comi; Giada Cosentino; Giulia Lanzolla; Francesca Menconi; Maglionico Maria Novella; Chiara Posarelli; Michele Figus; Rossella Elisei; Ferruccio Santini; Michele Marino

doi:10.1530/endoabs.101.OP-13-07

OP-13-07

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Endocrine Abstracts (2024) 101 OP13-07 | DOI: 10.1530/endoabs.101.OP-13-07

ETA2024 Oral Presentations Oral Session 13: TED (7 abstracts)

Long-term outcome of graves’ orbitopathy following treatment with sirolimus (RAPAMYCIN)

Simone Comi ¹ , Giada Cosentino ² , Giulia Lanzolla ³ , Francesca Menconi ⁴ , Maria Novella Maglionico ⁵ , Chiara Posarelli ⁶ , Michele Figus ⁷ , Rossella Elisei ¹ , Ferruccio Santini ¹ & Michele Marinò ⁸

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¹University of Pisa, Endocrinology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy; ²University of Pisa, Department of Clinical and Experimental Medicine, Endocrinology, Pisa, Italy; ³University of Pisa, Department of Clinical and Experimental Medicine, Endocrinology Unit Ii, Postdoctoral Research Fellow, University of Pennsylvania, Perelman Medical School, McKay Orthopaedic Research Laboratory, PhD Student, Department of Clinical and Translational Science, University of Pisa, Pisa, Italy; ⁴Endocrinology Unit, University of Pisa, University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy; ⁵Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Italy., Ophthalmology Unit, Italy; ⁶University of Pisa, Ophthalmology Unit, Department of Surgical, Medical and Molecular Pathology, Pisa, Italy; ⁷University of Pisa, Ophthalmology Unit I, Department of Surgical, Medical and Molecular Pathology, Pisa, Italy; ⁸Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Endocrinology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy

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.