Drug Treatment of ME/CFS: What have we learned since 2007?

Prof Olav Mella gave an overview of the last 10 years of research into autoantibody reduction as a treatment for ME/CFS. He first presented the research conducted by his team on rituximab and cyclophosphamide. These drugs are traditionally used in chemotherapy for cancer. Rituximab binds to the CD20 antigen on B cells and destroys them. Cyclophosphamide, on the other hand, also acts against plasmablasts that are refractory to rituximab. At the beginning of their studies, despite promising preliminary studies, including a positive phase II study, a randomised multicenter phase III trial (RituxME) failed to demonstrate any efficacy of rituximab compared to a placebo control group. This was despite Prof. Mella and his team having observed for many years that some ME/CFS sufferers experienced symptom improvement after cancer and rituximab treatment. Possible reasons for this could have been the lack of objective endpoints, too low a dosage, and placebo effects in all study arms. Furthermore, the diversity and variability of ME/CFS symptoms make it difficult to demonstrate efficacy across patient subgroups. The studies on rituximab were continued with higher dosages and prolonged administration of the drug and ultimately showed significantly better results. The cyclophosphamide studies were able to demonstrate, in some cases, lasting remissions and efficacy even after long-term ME/CFS disease (albeit with a less favorable side effect profile than typically observed in cancer therapy). It is noteworthy that all ME/CFS symptoms were affected by this therapy, indicating that a central component of the pathomechanism is being influenced. The team is continuing their research to develop therapeutic approaches targeting the autoimmune component of ME/CFS. They are currently focusing on long-lived plasma cells that can release (auto)antibodies into the blood for years or even a lifetime.