RESUMEN

CONTEXT: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. OBJECTIVE: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. MAIN OUTCOME MEASURES: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. RESULTS: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. CONCLUSION: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Asunto(s)

Alemtuzumab/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Tiroiditis Autoinmune/inducido químicamente , Adulto , Alemtuzumab/uso terapéutico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/patología , Pronóstico , Recurrencia , Estudios Retrospectivos , Tiroiditis Autoinmune/epidemiología , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Ghrelin is a peptide hormone that is primarily released from the stomach. It is best known for its role in appetite initiation. However, evidence also suggests that ghrelin may play a much wider role in energy homeostasis and glucose metabolism. It is known that exogenous ghrelin exerts an orexigenic signal via growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. However, blocking ghrelin signalling in the arcuate nucleus does not decrease feeding. Evidence now proposes that an alternative pathway for ghrelin's action is via the vagus nerve. Furthermore, it has been suggested that ghrelin signalling is an important physiological regulator of body adiposity and energy storage. Ghrelin also seems to be important in controlling glucose metabolism through action in the pancreatic islets of Langerhans, representing a promising novel therapeutic target in diabetes treatment. Despite these findings, further research in humans is required before ghrelin can be indicated as a therapeutic target in obesity or diabetes. This review summarises the current literature concerning ghrelin's physiological roles in energy and glucose homeostasis.