Publications

Intrathcal treatment with rituximab in progressive MS – an phase 1b study:

Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study.
Bergman J, Burman J, Gilthorpe J, Zetterberg H, Jiltsova E, Bergenheim T, et al
Neurology 2018 Nov;91(20):e1893-e1901

The study show that 1 of 7 had a treatment effect after one year, none had any differences in 6 biomarkers and one had a bacterial meningitis that was treated successfully.

The role of B cells in MS:

Faiez Al Nimer and Fredrik Piehl together with a group in Zürich have published an article in Cell about memory B cells in MS:

Memory B Cells Activate Brain-Homing, Autoreactive CD4 T Cells in Multiple Sclerosis.
Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R, Jelcic I, et al
Cell 2018 Sep;175(1):85-100.e23

You can read more about the article here (in Swedish): http://www.neurologiisverige.se/ny-forklaring-till-uppkomsten-av-ms/

In short, autoproliferation by CD4 T cells in MS, especially in DRB1*15:01 positive patients, is driven by memory B cells that are depleted by rituximab treatment. After 3-4 doses rituximab it seems like the memory B cell pool is eliminated and the question is how long lasting the effect might be then. Observations from both Umeå and Stockholm indicates that the risk for new disease activity over 2-3 years is very low, as one see with induction treatments with alemtuzumab and cadribine. This is of potential clinical importance, for example regarding sensitivity against infections and regarding vaccinations. If we see that your have a poor take on vaccination due to rituximab treatment one might be able to let the B cells return for a bit longer to improve the vaccination protection.

Combination of MRI and biomarkers in CSF can be used to predict secondary progressive disease.

Joachim Burman has together with colleagues in Uppsala published the following article:

Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis.
Herman S, Khoonsari P, Tolf A, Steinmetz J, Zetterberg H, Åkerfeldt T, et al
Theranostics 2018 ;8(16):4477-4490

In short, they have with the help of metabolites and protein analyses in CSF together with MRI data identified SPMS at an early stage. With 11 variables one could separate RRMS and SPMS and with an additional 4 markers even progression.

 

Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies.
Dunn N, Juto A, Ryner M, Manouchehrinia A, Piccoli L, Fink K, et al
Mult. Scler. 2018 Aug;24(9):1224-1233

 

Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis.
Granqvist M, Boremalm M, Poorghobad A, Svenningsson A, Salzer J, Frisell T, et al
JAMA Neurol 2018 Mar;75(3):320-327

 

Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS.
de Flon P, Laurell K, Söderström L, Gunnarsson M, Svenningsson A
Mult. Scler. 2017 Aug;23(9):1249-1257

 

Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy.
Salzer J, Svenningsson R, Alping P, Novakova L, Björck A, Fink K, et al
Neurology 2016 Nov;87(20):2074-2081

 

Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab.
de Flon P, Gunnarsson M, Laurell K, Söderström L, Birgander R, Lindqvist T, et al
Neurology 2016 Jul;87(2):141-7

 

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.
Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, et al
Ann. Neurol. 2016 Jun;79(6):950-8

 

Rituximab in paediatric onset multiple sclerosis: a case series.
Salzer J, Lycke J, Wickström R, Naver H, Piehl F, Svenningsson A
J. Neurol. 2016 Feb;263(2):322-326