Clinical Manifestation of Alemtuzumab-induced Autoimmune Thyroid Disease in People with Highly Active Multiple Sclerosis Is Dependent on Age and Presence of Early Brainstem Involvement (1292)

Objective: To analyze the clinical characteristics of alemtuzumab (ALZ)-induced autoimmune thyroid disease (AITD) in people with multiple sclerosis (pwMS). Background: Contributory factors for development of ALZ-induced AITD in pwMS are not well-characterized. Design/Methods: A retrospective chart review was performed for pwMS who received ≥ two ALZ cycles with follow-up of ≥ two years from first ALZ infusion (FAI). Results: Fifty-two ALZ-treated pwMS fulfilled criteria for inclusion of which 16 (30.8%) developed AITD over mean follow-up of 4.6 years (range 2.0–10.3). Graves’ Disease (GD) was observed in 56.3%, of which the majority (7/9, 77.8%) became symptomatic, requiring pharmacologic therapy. All but one with symptomatic GD experienced large and rapid swings in thyroid function tests (TFTs) despite small dose adjustments of carbimazole or levothyroxine. Three (42.9%) experienced recurrence of thyrotoxicosis after a prolonged period (4, 6, 30 months) of apparent remission; two (28.6%) are under consideration for thyroidectomy, one of whom was actively planning pregnancy. Mean±SD age at FAI of symptomatic GD cohort was 26.4±5.7 years, approximately 9.5 years (95% CI 1.7–17.2, p=0.02, d=1.4) younger than that for people with asymptomatic GD, silent thyroiditis and hypothyroidism combined (36.9±8.1 years). Age at FAI positively correlated with onset of AITD (r=0.51, p=0.04). Of 14 people with brainstem syndrome as first MS presentation, six (42.9%) developed AITD; all six have positive Thyroid-Stimulating Hormone (TSH)-Receptor antibodies; all but one (5/6) developed symptomatic GD (E¸=0.71, p=0.03). Conclusions: Where abnormal TFTs are detected among ALZ-treated pwMS, age≤32 years at FAI (p=0.03) and brainstem syndrome as first MS presentation appear to be associated with developing symptomatic GD, possibly due to early increased cross-reactivity between autoantigens expressed in the brainstem and thyroid. These findings, taken together with the elevated risk of adverse pregnancy outcomes in maternal AITD, suggest cautious use of ALZ in younger people with early brainstem involvement where alternative therapies are readily available. Disclosure: Dr. Yap has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Yap has received research support from Novartis.Dr. Dillon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Roche. Dr. Crowley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen. Dr. Crowley has received research support from Kyowa Kirin. Dr. McGuigan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honoraria for consultancy work and/or research funding from Actelion, Biogen, Merck, Novartis, Roche, Sandoz, and Sanofi-Genzyme. Dr. McGuigan has received research support from Honoraria for consultancy work and/or research funding from Actelion, Biogen, Merck, Novartis, Roche, Sandoz, and Sanofi-Genzyme.