Øystein Fluge

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Øystein Fluge, MD, is the Senior Consultant supervising the ME/CFS research group at the Department of Oncology and Medical Physics at the University of Bergen, Haukeland University Hospital, Bergen, Norway.[1] He works with Professor Olav Mella in the Norwegian Rituximab and cyclophosphamide trials employing the depletion of B cell lymphocytes in ME/CFS patients.

Dr. Fluge is a member of the Working Group which offers their expertise and resources to the ME/CFS Collaborative Research Center at Stanford University.[2]

Rituximab work in ME/CFS[edit | edit source]

Øystein Fluge's and Olav Mella's discovery was found by accident, in that three ME/CFS patients who had B-cell lymphoma improved remarkably following treatment with Rituximab. Not only had their lymphomas improved, but all symptoms of their ME/CFS diminished with the treatment. The positive responses were delayed for up to 6-12 weeks, despite their B cells being eliminated by the drug in 2 weeks. Since that accidental discovery, a larger study has been undertaken. Initial reports were promising in that there is a positive response in 67% of the patients receiving Rituximab vs a 13% improvement in the placebo group. After the effects wore off, there was a decline in the numbers who responded to the second and subsequent infusions.[3] The clinical trial, named RituxME, was a multicenter, phase III study. It was randomized, double-blind and placebo controlled, with 152 participants, of which half will receive treatments with rituximab and the other half will be treated with placebo (saline).[4]

On Nov 21, 2017, Drs. Øystein Fluge and Olav Mella announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The Drs. will publish a paper next year with the specifics of the failed trial.[5]

The discovery of ME/CFS patients responding positively to an autoimmunity drug has radically changed how many have viewed ME/CFS, to the point that Bjørn Guldvog, the Deputy Director General of Norwegian Directorate of Health, has apologized for the way in which ME patients in Norway have been treated: "I think that we have not cared for people with ME to a great enough extent. I think it is correct to say that we have not established proper health care services for these people, and I regret that." The European ME Alliance believes that such a public apology from a governmental health agency has never occurred before.[6]

In 2015, a second clinical trial for ME/CFS by the same group headed by Fluge and Mella, was started using the chemotherapy drug, cyclophosphamide. Called CycloME part A​, this study will involve 40 patients with moderate and severe ME/CFS and will be ongoing until January 2017. If the results indicate a clinically relevant response, i.e., an improvement in symptoms, in a minimum of 40% of the patients, the trial will move into CycloME part B and may be extended to include patients with very severe ME.[7]

Talks and Interviews[edit | edit source]

Notable ME/CFS Studies[edit | edit source]

  • 2011, Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study[8] - (Full text)
  • 2015, B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment[9] - (Full text)
  • 2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome[10] - (Full text)
  • 2016, Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome.[11]
  • 2016, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. The study abstract states: "The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS."[12]
  • 2018, Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)[13] - (Full text)
  • 2018, Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome[14] - (Abstract)
  • 2019, B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial[15]
  • 2019, Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome[16] - (Full text)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/Forsking-p%C3%A5-ME.aspx
  2. "OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University". bos.etapestry.com. Retrieved September 12, 2019.
  3. "Invest in ME Research - International ME Conferences and Colloquiums Home Page". investinme.org. Retrieved September 12, 2019.
  4. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/RituxME.aspx
  5. "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails". Simmaron Research. November 26, 2017. Retrieved September 12, 2019.
  6. "European ME Alliance - Norway's Directorate of Health Apologises to ME Patients for Poor Treatment". www.euro-me.org. Retrieved September 12, 2019.
  7. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/CycloME.aspx
  8. Fluge, Øystein; Bruland, Ove; Risa, Kristin; Storstein, Anette; Kristoffersen, Einar Klæboe; Sapkota, Dipak; Næss, Halvor; Dahl, Olav; Nyland, Harald Inge; Mella, Olav (2011), "Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.", PLoS One, 6 (10): e26358, doi:10.1371/journal.pone.0026358
  9. Fluge, Øystein; Risa, Kristin; Lunde, Sigrid; Alme, Kine; Rekeland, Ingrid Gurvin; Sapkota, Dipak; Kristoffersen, Einar Kleboe; Sørland, Kari; Bruland, Ove (July 1, 2015). van der Feltz-Cornelis, Christina (ed.). "B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment". PLOS ONE. 10 (7): e0129898. doi:10.1371/journal.pone.0129898. ISSN 1932-6203. PMC 4488509. PMID 26132314.
  10. Fluge, Øystein; Mella, Olav; Bruland, Ove; Risa, Kristin; Dyrstad, Sissel E.; Alme, Kine; Rekeland, Ingrid G.; Sapkota, Dipak; Røsland, Gro V.; Fosså, Alexander; Ktoridou-Valen, Irini; Lunde, Sigrid; Sørland, Kari; Lien, Katarina; Herder, Ingrid; Thürmer, Hanne; Gotaas, Merete E.; Baranowska, Katarzyna A.; Bohnen, Louis M.L.J.; Schäfer, Christoph; McCann, Adrian; Sommerfelt, Kristian; Helgeland, Lars; Ueland, Per M.; Dahl, Olav; Tronstad, Karl J. (2016), "Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome", JCI Insight, 1 (21), doi:10.1172/jci.insight.89376
  11. Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein (August 18, 2016). Cordero, Mario D. (ed.). "Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome". PLOS ONE. 11 (8): e0161226. doi:10.1371/journal.pone.0161226. ISSN 1932-6203.
  12. Loebel, M; Grabowski, P; Heidecke, H; Bauer, S; Hanitsch, LG; Wittke, K; Meisel, C; Reinke, P; Volk, H; Fluge, Ø; Mella, O; Scheibenbogen, C (2016), "Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome", Brain, behavior, and immunity, 52: 32-39, doi:10.1016/j.bbi.2015.09.013
  13. Günther, Oliver P.; Gardy, Jennifer L.; Stafford, Phillip; Fluge, Øystein; Mella, Olav; Tang, Patrick; Miller, Ruth R.; Parker, Shoshana M.; Johnston, Stephen A. (October 8, 2018). "Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Molecular Neurobiology. doi:10.1007/s12035-018-1354-8. ISSN 0893-7648.
  14. Schjøtt, Jan; Vries, Annick de; Mella, Olav; Sørland, Kari; Risa, Kristin; Alme, Kine; Fluge, Øystein; Rekeland, Ingrid G. (November 28, 2018). "Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome". Clinical Therapeutics. 0 (0). doi:10.1016/j.clinthera.2018.10.019. ISSN 1879-114X. PMID 30502905.
  15. Fluge, Øystein; Rekeland, Ingrid G.; Lien, Katarina; Thürmer, Hanne; Borchgrevink, Pette C.; Schäfer, Christoph; Sørland, Kari; Aßmus, Jörg; Ktoridou-Valen, Irini; Mella, Olav (April 2, 2019). "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial". Annals of Internal Medicine. doi:10.7326/M18-1451. ISSN 0003-4819.
  16. Giannoccaro, Maria Pia; Cossins, Judith; Sørland, Kari; Fluge, Øystein; Vincent, Angela (May 2019). "Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome". Clinical Therapeutics. 41 (5): 836–847. doi:10.1016/j.clinthera.2019.04.001.