TOPLINE

New research adds to evidence of an underrecognized link between the treatment of multiple sclerosis (MS) with immunomodulatory therapy and the subsequent development of thyroid eye disease (TED), often not emerging until several years following the treatment.

In light of the growing evidence, experts recommend that patients with MS who are treated with the therapy, especially alemtuzumab, should be monitored for potential eye disease for a minimum of 3-5 years.

METHODOLOGY

• The retrospective case series involved six patients treated for MS at Imperial College Healthcare NHS Trust, in London, England, who developed TED in the years following immunomodulatory therapy between 2015 and 2026.
• Of the patients, four were treated with alemtuzumab, one with natalizumab, and one with interferon-based therapy with intravenous methylprednisolone and cyclophosphamide.
• The patients all had normal thyroid levels and no prior history of Graves disease or TED prior to their immunotherapy treatment.
• Three patients reported never smoking, whereas one was a current and two were previous smokers, with smoking considered a suspected risk factor for thyroid dysfunction in general following treatment with alemtuzumab.

TAKEAWAY

• The median interval between treatment with immunomodulatory therapy and the development of TED was 38.5 months (range, 33-57 months), with TED developing following the exposure to treatment in all cases.
• At the time of TED diagnosis, all patients had been diagnosed with Graves disease, and four had suppressed concentrations of thyroid stimulating hormone (< .001 mU/L).
• At the time of presentation, one patient had mild TED, four had moderate disease, and one had severe TED, based on EUGOGO (European Group on Graves’ Orbitopathy) criteria. Disease severity subsequently advanced to severe in four of the patients.
• TED treatment included intravenous methylprednisolone in two patients and local triamcinolone injection in one patient; however, three of the patients required rehabilitative interventions, including strabismus surgery, orbital decompression, or eyelid surgery.

IN PRACTICE

The mechanisms driving the development of TED following alemtuzumab could include the “loss of immune tolerance during reconstitution, thyroid autoantibody generation, and subsequent orbital immune activation,” the authors noted.

Overall, the findings add to prior evidence indicating that “therapy-associated TED is a delayed complication of immune reconstitution therapy in MS,” said first author Sandhi W. Nyunt, MBBS, MPH, of Imperial College Healthcare NHS Trust.

Importantly, “disease severity may be underestimated by inflammatory activity alone,” she added.

“Long-term thyroid and ocular surveillance is essential after immune reconstitution therapy,” Nyunt said. “Early multidisciplinary referral may improve outcomes.”

SOURCE

The study was presented at ENDO 2026: The Endocrine Society Annual Meeting.

LIMITATIONS

As a single-center case series, the study was limited by its size.

However, previous data supporting the underrecognized link between alemtuzumab treatment in MS with TED is described in a recent systematic review of reported cases.

DISCLOSURES

Nyunt had no disclosures to report.