AUTHOR=Sandgren Sofia , Novakova Lenka , Axelsson Markus , Amirbeagi Firoozeh , Kockum Ingrid , Olsson Tomas , Malmestrom Clas , Lycke Jan 

TITLE=The role of autoimmune antibodies to predict secondary autoimmunity in patients with relapsing-remitting multiple sclerosis treated with alemtuzumab: A nationwide prospective survey

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1137665

DOI=10.3389/fneur.2023.1137665

ISSN=1664-2295

ABSTRACT=Background: Alemtuzumab (ALZ) is an immune reconstitution therapy for treating relapsing-remitting multiple sclerosis (RRMS). However, ALZ increases the risk of secondary autoimmune diseases (SAD). 

Objective: We explored whether the detection of autoimmune-antibodies (auto-Abs) could predict the development of SADs. 

Methods: We included all patients with RRMS in Sweden that initiated ALZ treatment (n=124, 74 females) from 2009-2019. Presence of auto-Abs were determined in plasma samples obtained at baseline and at 6, 12, and 24 months of follow-up, and in a subgroup of patients (n=51) also in plasma samples obtained at the remaining three months intervals up to 24 months. Monthly blood tests, urine tests, and assessment of clinical symptoms, were performed for monitoring safety including that of SADs. 

Results: Autoimmune thyroid disease (AITD) developed in 40% of patients, within a median follow-up of 4.5 years. Thyroid auto-Abs were detected in 62% of patients with AITD. The presence of thyrotropin receptor antibody (TRAbs) at baseline increased the risk of AITD by 50%. At 24 months, thyroid auto-Abs were detected in 27 patients, and 93% (25/27) developed AITD. Among patients without thyroid auto-Abs, only 30% (15/51) developed AITD (p<0.0001). In the subgroup of patients (n=51) with more frequent sampling for auto-Abs, 27 patients developed ALZ-induced AITD, and 19 of them had detectable thyroid auto-Abs prior to AITD onset, with a median interval of -216 days. Eight patients (6.5%) developed non-thyroid SAD, none had detectable non-thyroid auto-Abs. 

Conclusion: We conclude that, monitoring of thyroid auto-Abs, essentially TRAbs, may improve the surveillance of AITD associated with ALZ treatment. The risk for non-thyroid SADs was low, and monitoring non-thyroid auto-Abs did not seem to provide any additional information for predicting non-thyroid SADs.