ORF49-03 - Thyroid Eye Disease Following Immunomodulatory Therapy for Multiple Sclerosis: A Case Series

Background
Immunomodulatory therapies used in multiple sclerosis (MS) induce major changes in adaptive immunity. Immune reconstitution therapy can disrupt immune tolerance and is well known to cause secondary autoimmune disease, most commonly autoimmune thyroid disease such as Graves’ disease (GD). In contrast, clinically significant thyroid eye disease (TED) following these therapies is rarely reported and remains poorly characterized. Immune reconstitution after alemtuzumab can promote thyroid autoantibody production and orbital autoimmunity, providing a plausible mechanism for treatment-associated TED.
Methods
We conducted a retrospective case series of patients with MS who developed TED following immunomodulatory therapy. Patients were identified through a specialist TED multidisciplinary clinic at Imperial College Healthcare NHS Trust. Data collected included demographics, thyroid function and autoantibody status, TED severity and progression, investigations, management strategies and MS-related clinical features and treatments.
Results
Six patients with MS developed TED following immunomodulatory therapy: alemtuzumab (n=4), natalizumab (n=1), and interferon-based therapy with intravenous methylprednisolone and cyclophosphamide (n=1). All patients were euthyroid and had no prior history of GD or TED before immunotherapy. 3 patients never smoked while 1 was a current and 2 was a previous smoker.
TED developed after treatment exposure in all cases. Among alemtuzumab-treated patients, TED onset occurred at a median of 36 months following therapy (IQR 24–48 months). All patients were diagnosed with GD and had positive thyrotropin receptor antibodies. At TED diagnosis, four patients had suppressed TSH concentrations ( < 0.001 mU/L).
At presentation, TED severity by EUGOGO criteria ranged from mild (n=1) to moderate (n=4) and severe (n=1). Disease progression was observed, with peak severity reaching severe disease in four patients. TED treatment included intravenous methylprednisolone (n=2) and local triamcinolone injection (n=1). Three patients required rehabilitative interventions, including strabismus surgery, orbital decompression, or eyelid surgery. GD was managed with antithyroid drugs (n=3) or thyroidectomy (n=3).
Conclusions
This case series indicates that immunomodulatory therapy for MS, particularly immune reconstitution therapy with alemtuzumab, may predispose patients to clinically significant TED in addition to secondary thyroid autoimmunity. Loss of immune tolerance during reconstitution, thyroid autoantibody generation, and subsequent orbital immune activation likely contribute to disease development. These findings support extended thyroid and ocular surveillance for at least 3–5 years after treatment, with early evaluation of ocular symptoms and timely referral to specialist multidisciplinary services.