Wohlrab et al. (2025)
- Authors: Felix Wohlrab, Mailam Eltity, Friederike Ufer, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl
- Institutes: Experimental and Clinical Research Center, A Cooperation Between Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Experimental and Clinical Research Center, Berlin, Germany; Clinic for Neurology and Experimental Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
- Publisher: Expert Opinion on Biological Therapy
- Link: DOI
Summary
This review consolidates the idea that for a subset of ME/CFS and Post-COVID patients, the illness may be driven by an autoimmune process involving harmful antibodies. It explains that clinical trials for treatments targeting these antibodies have produced mixed results, likely because they were tested on broad patient groups rather than just those with clear signs of autoimmunity. The key message is that future research must focus on using biomarkers to identify the right patients for these specific therapies, a strategy that could finally lead to effective, personalized treatments for this subgroup of patients.
What was researched?
This editorial reviews the current evidence for therapies that target autoantibodies (AAbs) as a potential treatment strategy for Post-COVID Syndrome (PCS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It summarizes the results of clinical trials for various immunomodulatory drugs and procedures.
Why was it researched?
There is mounting evidence suggesting that autoimmunity, specifically the presence of harmful autoantibodies, plays a role in a subset of patients with PCS and ME/CFS. As there are no approved causal therapies for these conditions, exploring treatments that can remove or neutralize these autoantibodies is considered one of the most promising avenues for developing effective interventions.
How was it researched?
This article is an expert opinion and literature review. The authors analyzed and summarized the findings from various clinical trials and observational studies investigating AAb-targeting therapies. The treatments reviewed include B-cell depleting agents like rituximab 💊, immunoadsorption 💊, intravenous immunoglobulins 💊 (IVIG), and newer drugs such as daratumumab 💊, efgartigimod, and rovunaptabin (BC007).
What has been found?
The review found mixed results across different AAb-targeting therapies. While early-phase trials of rituximab and observational studies of immunoadsorption and IVIG showed promising results in some ME/CFS and PCS patients, subsequent larger or controlled trials have often been disappointing. For instance, a phase III trial of rituximab failed to show significant benefits, and recent phase II trials of efgartigimod and rovunaptabin in PCS also failed to meet their primary endpoints. Preliminary results for daratumumab are encouraging but very early.
Discussion
The authors argue that a major reason for the inconsistent and often negative trial results is the failure to account for the heterogeneity of these illnesses. Most studies did not select patients based on evidence of autoimmunity, such as the presence of specific AAbs. This lack of patient stratification likely led to the inclusion of patients whose disease is not driven by autoantibodies, thereby diluting any potential treatment effect and contributing to trial failures.
Conclusion & Future Work
The authors conclude that AAb-targeting therapy remains a promising strategy for a specific subgroup of PCS and ME/CFS patients. To move forward, future clinical trials must be designed with better patient selection criteria. They suggest using biomarkers, such as specific autoantibodies or a positive response to a preliminary treatment like immunoadsorption, to identify patients with a high likelihood of an AAb-mediated disease before enrolling them in trials for B-cell depleting therapies.