Rituximab

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. It has been suggested patients who respond to Rituximab have an autoimmune disease.

Accidental ME/CFS Treatment Discovery
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.

As of 2015 we have no formal proof that rituximab is 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.

Published Studies

 * 2015, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome (Øystein Fluge, Olav Mella, Loebel M, Grabowski P, Heidecke H, Bauer S, Hanitsch LG, Wittke K, Meisel C, Reinke P, Volk HD, Carmen Scheibenbogen)
 * 2015, B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment (Øystein Fluge, Olav Mella, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sørland K, Bruland O, Dahl O)
 * 2013, Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls (Amolak Bansal, AS Bradley, B Ford)
 * 2011, Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study (Øystein Fluge, Olav Mella, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H)
 * 2009, Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series (Øystein Fluge, Olav Mella)

Ongoing Studies

 * [Invest in ME are planning a Rituximab study in the UK.
 * The Norwegian team are running more trials:
 * Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS) (CycloME) (see Cyclophosphamide)
 * B-lymphocyte Depletion Using Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Randomized Phase-III Study. (RituxME)
 * B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome

Risks & Side Effects
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.

Private Availability
Patients have stated that Rituximab is being offered to ME/CFS patients in the United States (Andreas Kogelnik) and in Norway (a private clinic in Sandnes) 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".

Talks & Interviews

 * Dr. Kenneth J. Friedman, discusses the drug Rituximab for those with ME/CFS (23 Jun 2014)
 * Olav Mella speaks about the Rituximab study and ME/CFS future (12 May 2014)
 * Chronic Fatigue Syndrome: Study Supports Autoimmune Disease Theory (ABC News, 24 October 2011)
 * Immune system defect may cause ME (BBC News, 24 October 2011)
 * Chronic fatigue syndrome eased by cancer drug (New Scientist, 19 October 2011)

Media Coverage

 * The Biggest Chronic Fatigue Syndrome Treatment Trial Begins: Fluge/Mella On Rituximab (20 January 2015)
 * B cell depletion benefits ME/CFS patients (Virology Blog, 9 July 2015)
 * Antibody wipeout found to relieve chronic fatigue syndrome (New Scientist, 1 July 2015)
 * Norwegian TV update on study (2013)