Midtveisevaluering - Brit Ellen Rød

Brit Ellen Rød er tilknyttet Klinisk institutt 1. Veiledere er Stig Wergeland og Øivind Torkildsen.

Prosjekt

Anti-CD20 therapy for multiple sclerosis – effectiveness and risks

Abstract

Anti-CD20 therapy is widely used to treat autoimmune diseases, and it is effective against relapsing-remitting multiple sclerosis (RRMS)(1). It is an anti-CD20 immunoglobulin G, and binding to its ligand on B-cells results in cytotoxicity. Why B cell depletion is effective in MS is still unknown.

Recently, the role of Epstein-Barr virus (EBV) as a causal agent for MS has become evident: it seems EBV is a prerequisite for disease development(2). After primary infection, the virus is latent throughout the lifetime of the host and the primary reservoir is the memory B-cells(3,4). As EBV is latent, it might not only be a trigger, but also a driver for the disease activity in MS(5). If so, can depletion of the EBV-infected memory-B cells halt MS activity?

To study immunological responses towards EBV during treatment with anti-CD20, we have followed a cohort of newly diagnosed, treatment naïve patients with MS participating in a phase 3 clinical study on the efficacy of anti-CD20 therapy for MS. Prospective serum samples during the two year follow-up period have been analyzed for changes in anti-EBV antibodies and EBV DNA levels. We have received results from the majority of samples, but are awaiting for the results from the final follow-up samples. When all results are ready, we will start the statistical analyses and manuscript preparation. To our knowledge, this will be the first study of a treatment naïve cohort, where their humoral response to EBV during anti-CD20 therapy is studied. The results may inform further research on MS therapy, e.g. effect of antiviral therapy or therapeutic vaccines on MS risk and activity.
 
The use of anti-CD20 therapy for MS is increasing, and the target patient population includes women of childbearing potential. Safety of breastfeeding during treatment is therefore of great interest, but scarcely described in the literature. We have published a case series(6) of six mother-infant pairs, where the nursing mothers received rituximab during breastfeeding. A unique collection of serial samples, including serum samples from the infants, reveals minimal transfer of rituximab into breastmilk (median relative infant dose of 0.07%) and not detectable rituximab levels in the infants’ serum. The infants’ B cell counts were unaffected. Our results support mothers treated with rituximab to breastfeed.

References:

1. Granqvist M, Boremalm M, Poorghobad A, et al. Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurol 2018;75(3):320-27. doi: 10.1001/jamaneurol.2017.4011 [published Online First: 2018/01/09]

2. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022 doi: 10.1126/science.abj8222 [published Online First: 2022/01/14]

3. Houen G, Trier NH. Epstein-Barr Virus and Systemic Autoimmune Diseases. Front Immunol 2020;11:587380. doi: 10.3389/fimmu.2020.587380 [published Online First: 2021/01/26]

4. Young LS, Yap LF, Murray PG. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer 2016;16(12):789-802. doi: 10.1038/nrc.2016.92 [published Online First: 2016/11/04]

5. Sollid LM. Epstein-Barr virus as a driver of multiple sclerosis. Sci Immunol 2022;7(70):eabo7799. doi: 10.1126/sciimmunol.abo7799 [published Online First: 2022/04/02]

6. Rød BE, Torkildsen Ø, Myhr KM, et al. Safety of breast feeding during rituximab treatment in multiple sclerosis. J Neurol Neurosurg Psychiatry 2022 doi: 10.1136/jnnp-2022-329545 [published Online First: 2022/07/26]