Publications COMBAT-MS

Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies.
Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al
JAMA Neurol 2020 Feb;77(2):184-191

Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Spelman T, Frisell T, Piehl F, Hillert J. Mult Scler. 2018 Jul;24(8):1087-1095. doi: 10.1177/1352458517713668. PMID: 28649912

Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients.
Alping P, Askling J, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al Ann Neurol 2020 05;87(5):688-699

Rituximab, MS, and pregnancy. Smith JB, Hellwig K, Fink K, Lyell DJ, Piehl F, Langer-Gould A.Neurol Neuroimmunol Neuroinflamm. 2020 May 1;7(4):e734. doi: 10.1212/NXI.0000000000000734. Print 2020 Jul. PMID: 32358226

Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS.
Granqvist M, Burman J, Gunnarsson M, Lycke J, Nilsson P, Olsson T, Sundström P, Svenningsson A, Vrethem M, Frisell T, Piehl F. Mult Scler. 2020 Oct;26(12):1532-1539. doi: 10.1177/1352458519866600. PMID: 31392923

Neurological manifestations of coronavirus infections - a systematic review.
Almqvist J, Granberg T, Tzortzakakis A, Klironomos S, Kollia E, Öhberg C, et al Ann Clin Transl Neurol 2020 10;7(10):2057-2071

Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis.
Granberg T, Moridi T, Brand JS, Neumann S, Hlavica M, Piehl F, et al
J Neurol 2020 Jun;():

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab.
Razaz N, Piehl F, Frisell T, Langer-Gould AM, McKay KA, Fink K. Neurol Neuroimmunol Neuroinflamm. 2020 Oct 21;7(6):e903. doi: 10.1212/NXI.0000000000000903. Print 2020 Nov. PMID: 33087582

Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis.
Piehl F. J Intern Med. 2021 Jun;289(6):771-791. doi: 10.1111/joim.13215. PMID: 33258193

Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis.
Alping P, Burman J, Lycke J, Frisell T, Piehl F. Neurology. 2021 Mar 16;96(11):e1574-e1584. doi: 10.1212/WNL.0000000000011545. PMID: 33514645

Risk of depression in multiple sclerosis across disease-modifying therapies.
Longinetti E, Frisell T, Englund S, Reutfors J, Fang F, Piehl F. Mult Scler. 2021 Jul 15:13524585211031128. doi: 10.1177/13524585211031128. PMID: 34264143

Neurofilament light chain as a marker for cortical atrophy in multiple sclerosis without radiological signs of disease activity.
Ineichen BV, Moridi T, Ewing E, Ouellette R, Manouchehrinia A, Stawiarz L, Ferreira D, Muehlboeck SJ, Kuhle J, Westman E, Leppert D, Hillert J, Olsson T, Kockum I, Piehl F, Granberg T. J Intern Med. 2021 Aug;290(2):473-476. doi: 10.1111/joim.13286. PMID: 33871105

Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis
Xu Y, Smith KA, Hiyoshi A, Piehl F, Olsson T, Montgomery S. Brain. 2021 Sep 4;144(8):2390-2400. doi: 10.1093/brain/awab100. PMID: 33693538

Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients With Relapsing-Remitting Multiple Sclerosis: Data From 2 Different National Strategies
Spelman T, Magyari M, Piehl F, Svenningsson A, Rasmussen PV, Kant M, Sellebjerg F, Joensen H, Hillert J, Lycke J. JAMA Neurol. 2021 Oct 1;78(10):1197-1204. doi: 10.1001/jamaneurol.2021.2738. PMID: 34398221

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis.
Ouellette R, Mangeat G, Polyak I, Warntjes M, Forslin Y, Bergendal Å, et al Ann Neurol 2020 05;87(5):710-724
Platten M, Martola J, Fink K, Ouellette R, Piehl F, Granberg T
J Neuroimaging 2020 03;30(2):198-204

Rituximab treatment for multiple sclerosis.
Ineichen BV, Moridi T, Granberg T, Piehl F
Mult Scler 2020 02;26(2):137-152

Validation of the Swedish Multiple Sclerosis Register: Further Improving a Resource for Pharmacoepidemiologic Evaluations.
Alping P, Piehl F, Langer-Gould A, Frisell T,
Epidemiology 2019 03;30(2):230-233

Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis.
Boremalm M, Juto A, Axelsson M, Novakova L, Frisell T, Svenningsson A, et al Eur J Neurol 2019 08;26(8):1060-1067

Neuroimaging projects

7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis
Russell Ouellette, Constantina A. Treaba, Tobias Granberg, Elena Herranz, Valeria Barletta, Ambica Mehndiratta, Benjamin De Leene, Shahamat Tauhid, Fawad Yousuf, Sarah M. Dupont, Eric C. Klawiter, Jacob A. Sloane, Rohit Bakshi, Julien Cohen-Adad and Caterina Mainero. BRAIN 2020: 143; 2973–2987

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosisz
Ouellette R, Mangeat G, Polyak I, Warntjes M, Forslin Y, Bergendal Å, Plattén M, Uppman M, Treaba CA, Cohen-Adad J, Piehl F, Kristoffersen Wiberg M, Fredrikson S, Mainero C, Granberg T. Ann Neurol. 2020 May;87(5):710-724. doi: 10.1002/ana.25705. PMID: 32057118

Deep Learning Corpus Callosum Segmentation as a Neurodegenerative Marker in Multiple Sclerosis
Michael Platten , Irene Brusini, Olle Andersson, Russell Ouellette , Fredrik Piehl, Chunliang Wang, Tobias Granberg. J Neuroimaging 2021;31:493-500. DOI: 10.1111/jon.12838

MRI-Based Manual versus Automated Corpus Callosum Volumetric Measurements in Multiple Sclerosis
Michael Platten , Juha Martola, Katharina Fink, Russell Ouellette, Fredrik Piehl, Tobias Granberg. J Neuroimaging 2020;30:198-204. DOI: 10.1111/jon.12676

Cortical and white matter lesion topology influences focal corpus callosum atrophy in multiple sclerosis
Michael Platten, Russell Ouellette, Elena Herranz, Valeria Barletta, Constantina A. Treaba, Caterina Mainero, Tobias Granberg. J Neuroimaging. 2022;1–9. DOI: 10.1111/jon.12977

Automatic deep learning multicontrast corpus callosum segmentation in multiple sclerosis.
Irene Brusini, Michael Platten, Russell Ouellette, Fredrik Piehl, Chunliang Wang, Tobias Granberg. J Neuroimaging. 2022;1–12. DOI:10.1111/jon.12972

COVID enhancement projects:

Multiple sclerosis, rituximab, and COVID-19.
Annette Langer-Gould, Jessica B. Smith, Bonnie H. Li, the KPSC MS Specialist Group, Brandon E Beaber, Sonu M Brara, Julie Debacker, Allen Scott Nielsen, Samira Amirova & Oluwasheyi Ayeni. Annals of Clinical and Translational Neurology 2021; 8(4): 938–943

Rituximab infusion timing, cumulative dose, and hospitalization for COVID-19: Evidence from the nationwide COMBAT-MS Cohort
Kyla A McKay, Fredrik Piehl, Simon Englund, Anna He, Annette Langer-Gould, Jan Hillert, Thomas Frisell. JAMA accepted

Development of humoral and cellular immunological memory against SARS-CoV-2 despite B-cell depleting treatment in multiple sclerosis
Klara Asplund Högelin, Nicolas Ruffin, Elisa Pin, Anna Månberg, Sophia Hober, Guro Gafvelin, Hans Grönlund, Peter Nilsson, Mohsen Khademi, Tomas Olsson, Fredrik Piehl, Faiez Al Nimer. ISCIENCE (2021)

False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases.
Kharlamova N, Dunn N, Bedri SK, Jerling S, Almgren M, Faustini F, Gunnarsson I, Rönnelid J, Pullerits R, Gjertsson I, Lundberg K, Månberg A, Pin E, Nilsson P, Hober S, Fink K, Fogdell-Hahn A. Front Immunol. 2021 May 3;12:666114. doi: 10.3389/fimmu.2021.666114. eCollection 2021. PMID: 34012450

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 09;175(1):85-100.e23

(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 PE, 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 08;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 03;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