Alemtuzumab induces severe orbitopathy in relapsing–remitting multiple sclerosis

Context Treatment with Alemtuzumab (ALZ) in patients with Relapsing–Remitting Multiple Sclerosis (RRMS) is associated with the development of ALZ-induced Graves' disease (GD-ALZ). Some cases may develop associated Graves´ Orbitopathy (GO-ALZ), with possible visual compromise. Aim The aim of this study was to describe the main clinical and biochemical characteristics of GD-ALZ, as well as the clinical course of a case series of GO-ALZ Methods This study is a retrospective observational study, carried out in a reference hospital for the care of patients with RRMS in Spain. Cases treated with ALZ in the period 2014–2022 were included. GO-ALZ cases were identified among those with clinical symptoms compatible with thyroid eye disease after initiating ALZ treatment. Results A total of 135 cases, with a mean follow-up of 69.6 months after the first ALZ cycle, were included. The incidence of GD-ALZ was 32.6% (44/135), with a predominance of women (77.3%) and mean age of 41.9 years. The presence of first-degree relatives with hypothyroidism was identified as risk factor for the development of GD-ALZ (adjusted P-value: 0.02). GO-ALZ was diagnosed in 6 cases (incidence: 13.6%), of which 3 had severe clinical forms of GO, requiring anti-IL-6 treatment. A favorable response was reported in all of them, with a significant decrease in disease activity and improvement in proptosis. Conclusions We report one of the largest cohorts of GD-ALZ and GO-ALZ cases. The diagnosis of these entities should be taken into account in patients treated with Alemtuzumab, given the risk of developing severe clinical forms. In moderate-severe forms of GO-ALZ, drugs with anti-IL-6 activity are a safe and effective option.