From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
Jump to: navigation, search

Rituximab (trade names Rituxan, MabThera and Zytux) is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. It is in trials for use as a potential treatment for some ME/CFS patients.[1] It has been suggested patients who respond to Rituximab have an autoimmune disease. It is also in trials as a treatment for Multiple Sclerosis.[2]

Medical uses[edit | edit source]

Rituximab is used to treat cancers of the white blood system such as leukemias and lymphomas, including non-Hodgkin's lymphoma and lymphocyte predominant subtype of Hodgkin's Lymphoma. Rituximab has been shown to be an effective rheumatoid arthritis and is now licensed for use in refractory rheumatoid disease. It is used off-label to treat multiple sclerosis, systemic lupus erythematosus and chronic fatigue syndrome.

Rituximab may be effective in completely eliminating Epstein-Barr virus infection from the peripheral blood.[3]

Accidental ME/CFS treatment discovery[edit | edit source]

Two Norwegian oncologists, Øystein Fluge & Olav Mella, explain the history in their 2009 paper: "A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion". This discovery led to them running a series of trials examining the efficacy of Rituximab for treating ME/CFS.[4]

As of 2015 we had no formal proof that rituximab was effective for ME/CFS. The primary endpoint, at 3 months, of the randomised controlled trial published in 2011 was not met - there appeared to be no effect. However, at 6 months there did appear to be a significant benefit. In other autoimmune diseases rituximab can take many weeks to have effect and it is quite possible that in ME/CFS patients it has an effect that tends to take more than 3 months to show itself. So the 6 month endpoint is important. However, being a post-hoc analysis (i.e. in retrospect) the results do not provide formal statistical evidence for efficacy. A larger phase 3 trial is now in progress to establish formally whether or not the drug has a useful effect.

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]

Mode of action[edit | edit source]

Rituximab works in autoimmune disease by destroying memory B cells committed to producing autoantibodies that cause symptoms and signs of disease. The drug binds to the surface of the B cell by attaching to the CD20 molecule. This triggers cell death through several mechanisms including antibody dependent cytotoxicity and apoptosis. If the drug is infused slowly, B cells are removed without causing any unpleasant symptoms. Rituximab cannot target autoreactive cells specifically so it leads to depletion of memory B cells as a whole. This is probably not associated with major immunosuppression because antibodies to microbes are mostly made by long lived plasma cells derived in the past from memory B cells and these are not targeted by rituximab. Autoantibodies appear often to be produced by shorter lived plasma cells which die off rapidly.

B cell depletion with rituximab tends to last about 6 months. After that, when B cells return some patients will suffer an immediate relapse of autoimmune symptoms but others may continue well for a period of months or years and for some conditions apparently long term. So far it is unclear whether or not any effect in ME/CFS can continue long term or whether repeated treatment will be required, as is the case, for instance, for rheumatoid arthritis.

Risks & side effects[edit | edit source]

Rituximab is given by infusion in a hospital. Unwanted effects are not common but can be serious. Allergic reactions can normally be avoided by careful monitoring while giving the infusion very slowly at first. Sterile pneumonia-like episodes can occur within a few days after infusions. Susceptibility to infection may be increased if there are other reasons for being at risk but in general immunosuppression is not a major problem. [6]

Rarely, the temporary immunosuppression caused from Rituximab may cause a reactivation of a persistent enteroviral infection with potentially dangerous central nervous system complications.[7] Another rare but usually fatal viral disease triggered in a weakened immune system during the use of Rituximab is Progressive Multifocal Leukoencephalopathy (PML), caused by the the human polyomavirus John Cunningham virus (JCV). PML is being researched by Dr. Eugene Major, a member of the NIH Post-Infectious ME/CFS Study. [8]

Private availability[edit | edit source]

Patients have stated that Rituximab is being offered to ME/CFS patients in the United States (Andreas Kogelnik at the Open Medicine Institute) and in Norway (a private clinic in Sandnes)[9] but Jonathan Edwards has advised against this, stating in 2015 "As the person who established that rituximab is useful in autoimmune disease I would actually advise against this. Rituximab is very unlike most drugs in that you have to understand how to use it in considerable detail in order to give it safely and effectively".[10][11] The British patient charity the ME Association has also advised against patients looking for treatment with the drug outside of clinical trials.[12]

Evidence[edit | edit source]

Ongoing studies[edit | edit source]

Talks & interviews[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Fluge, Øystein; Risa, Kristin; Lunde, Sigrid; Alme, Kine; Rekeland, Ingrid Gurvin; Sapkota, Dipak; Kristoffersen, Einar Kleboe; Sørland, Kari; Bruland, Ove; Dahl, Olav; Mella, Olav (2015-07-01), "B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment", PLOS ONE, 10 (7): –0129898, doi:10.1371/journal.pone.0129898, ISSN 1932-6203, retrieved 2016-11-14 
  2. Multiple Sclerosis Society - Rituximab
  3. Diamantopoulos, Panagiotis T.; Polonyfi, Katerina; Sofotasiou, Maria; Papadopoulou, Vasiliki; Kalala, Fani; Iliakis, Theodoros; Zervakis, Kostantinos; Tsilimidos, Gerassimos; Kouzis, Panagiotis; Kyrtsonis, Marie-Christine; Vassilakopoulos, Theodoros; Angelopoulou, Maria; Siakantaris, Marina; Vayopoulos, George; Kollia, Panagoula; Pangalis, Gerassimos; Viniou, Nora-Athina (December 2013), "Rituximab in the treatment of EBV-positive low grade B-cell lymphoma", Anticancer Research, 33 (12): 5693–5698, ISSN 1791-7530, PMID 24324119 
  4. Fluge, Øystein; Mella, Olav (2009-07-01), "Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series", BMC neurology, 9: 28, doi:10.1186/1471-2377-9-28, ISSN 1471-2377, PMID 19566965 
  5. http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/
  6. Cancer Research UK - Rituximab (Mabthera)
  7. http://www.sciencedirect.com/science/article/pii/S0042682210007683
  8. Major EO. (2010). Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies. Annu Rev Med. 2010;61:35-47. doi: 10.1146/annurev.med.080708.082655.
  9. NRK television, Norway (27 Nov 2015), A private clinic in Sandnes, Norway is treating ME with Rituximab (video) 
  10. Phoenix Rising - Is there any way I can be treated with rituximab privately?
  11. Phoenix Rising - De Meirleir is using Rituximab?
  12. The ME Association - Rituximab – update by The ME Association | 23 May 2016
  13. Mensah, Fane; Bansal, Amolak; Berkovitz, Saul; Sharma, Arti; Reddy, Venkat; Leandro, Maria; Cambridge, Geraldine (2016), "Extended B cell phenotype in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A cross-sectional study", Clinical and Experimental Immunology, 184 (2): 237-247, doi:10.1111/cei.12749 
  14. UK Rituximab Trial
  15. http://www.investinme.org/IIMER-Newslet-1802-01.shtml
  16. UK Rituximab Trial - Statements By Professor Jonathan Edwards and Invest in ME | July 2013
  17. ME Action - NIH Considering Ampligen and Rituximab Trials | 21 December 2015

The information provided at this site is not intended to diagnose or treat any illness.

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history