CONTEXT: Alemtuzumab, an anti-CD52 monoclonal antibody, increased the risk of 
thyroid dysfunction in CAMMS223, a phase 2 trial in relapsing-remitting multiple 
sclerosis.
OBJECTIVE: The objective of the study was a detailed description of thyroid 
dysfunction in CAMMS223.
DESIGN: Relapsing-remitting multiple sclerosis patients (n=334) were randomized 
1:1:1 to 44 μg sc interferon-β-1a (SC IFNB-1a, Rebif) or annual courses of 12 or 
24 mg iv alemtuzumab. Thyroid function tests (TSH, free T3, free T4) and 
thyrotropin-binding inhibitory immunoglobulin (TBII) were assessed at screening, 
month 1, and quarterly thereafter; antithyroid peroxidase antibodies were 
assessed at screening and every 6 months. Thyroid dysfunction episodes were 
categorized post hoc by an endocrinologist.
RESULTS: During a median follow-up of 57.3 months, 34% of alemtuzumab and 6.5% 
of SC IFNB-1a patients had thyroid dysfunction (P<.0001). Ten percent of 
alemtuzumab and 3% of SC IFNB-1a patients had more than one episode of thyroid 
dysfunction. With alemtuzumab, Graves' hyperthyroidism occurred in 22%, 
hypothyroidism in 7%, and subacute thyroiditis in 4%. Of patients with overt 
Graves' hyperthyroidism, 23% spontaneously became euthyroid and an additional 
15% spontaneously developed hypothyroidism. Of patients with overt 
hypothyroidism, 74% were TBII positive. The annual incidence of a first episode 
of thyroid dysfunction increased each year through year 3 and then decreased 
each subsequent study year.
CONCLUSIONS: Thyroid dysfunction was more common with alemtuzumab than with SC 
IFNB-1a. There were few serious episodes. Regular monitoring facilitated early 
detection. Unique features of this population included high prevalence of 
Graves' hyperthyroidism, multiple episodes of thyroid dysfunction in individual 
patients, spontaneous hypothyroidism after overt Graves' hyperthyroidism, and a 
high prevalence of TBII-positive overt hypothyroidism.