Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Post-acute infection syndromes (PAIS) are long-lasting health problems that can develop after an infection. They include post-COVID-19 syndrome and similar illnesses following other infections. Some people with PAIS develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a serious and disabling illness that can greatly limit everyday activities. People with ME/CFS may experience severe fatigue, reduced physical and mental function, pain, sleep problems, and problems with the regulation of heart rate and blood pressure. A key feature is post-exertional malaise (PEM), in which symptoms become worse after physical or mental activity. The biological causes of PAIS and ME/CFS are not fully understood, and there is currently no established treatment that targets the underlying disease process. Research suggests that changes in the immune system may contribute to PAIS and ME/CFS in some patients. In particular, B cells (a type of immune cell) and autoantibodies (antibodies that react with the body's own structures) may play a role. Previous studies of immunoadsorption, a procedure that removes antibodies from the blood, have shown improvements in some patients with ME/CFS. These findings support further investigation of treatments that target B cells in selected patients. The PIONEER\_PAIS study will investigate whether inebilizumab can improve physical function in adults with PAIS who meet the diagnostic criteria for ME/CFS. The study includes a selected group of patients with evidence of autoantibodies and immune activation who previously improved after immunoadsorption but later experienced worsening of their symptoms. Inebilizumab is a monoclonal antibody that targets CD19, a protein found on B cells, and leads to the depletion of these cells. Participants will be randomly assigned to receive either inebilizumab or placebo (saline solution) as an infusion into a vein. Inebilizumab will be given at a dose of 300 mg on Day 1, Day 15, and Week 24. The study is double-blind, meaning that neither the participants nor the study team assessing them will know which treatment they receive. The main research question is whether treatment with inebilizumab leads to a greater improvement in physical function (PF) than placebo. PF will be measured using the PF scale of the SF-36 health questionnaire, comparing the change from the start of the study to Month 9 (Week 36). The study will also examine other aspects of health and daily functioning, including fatigue, post-exertional malaise, pain and headache, disability, symptoms related to the autonomic nervous system, muscle strength and fatigability, heart rate and blood pressure responses during standing, daily step count, and cognitive function. Adverse events will be monitored to assess the safety of the treatment. In addition, the study includes biomarker research focusing on B cells, autoantibodies, and other markers in the blood. This research aims to explore biological characteristics that may be associated with response to treatment and may help inform future studies of B-cell-targeted treatment in PAIS and ME/CFS.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe, often infection-triggered disease characterized by debilitating fatigue and post-exertional malaise lasting over 14 hours, along with pain, cognitive impairment, autonomic dysfunction, and sleep disturbances. Around 10% of patients after mild or moderate COVID-19 develop Post-COVID Syndrome (PCS), and some meet ME/CFS criteria after six months. No causal treatment exists for ME/CFS or PCS; current approaches are symptomatic and rehabilitative. Given the high and increasing number of affected patients, there is an urgent need for evidence-based, standardized therapies. Immunoadsorption (IA) is an established treatment for several autoimmune diseases. The first study demonstrating successful IA use in PCS-associated ME/CFS was published by our group in 2024. Earlier proof-of-concept studies (2018, 2020) in infection-related ME/CFS also showed symptomatic improvement in most patients. Hypothesis: Antibody depletion through IA improves symptoms in the majority of patients with autoantibody-positive ME/CFS and is associated with altered memory B-cell profiles before treatment. Objective: To observe and document symptom progression in 50 ME/CFS or PCS patients undergoing IA, and to examine whether changes in memory B-cells before treatment are linked to therapeutic response. The study is conducted as a non-interventional observational study. IA using the TheraSorb® column (Miltenyi) is performed within its approved clinical application.