Rituximab as therapy for autoantibody mediated fibromyalgia (RAFT), randomised double-blind placebo controlled randomised trial (RCT)

Fibromyalgia (FM) is defined by chronic widespread pain, disturbed sleep and fatigue. Prevalence of FM is about 2-8%. There is no disease modifying treatment (DMT) available for FM. FM is a major burden for patients, and also for society due to costs for healthcare and disability pension.

Researchers from KI and the UK recently made breaking discoveries that explain causative mechanisms in a subset of FM patients [1, 9].

They showed that up to 50% of FM patients carry autoantibodies (FM-Ab) which target dorsal root ganglia (DRG) surrounding cells and mediate pain-inducing molecular mechanisms.

This insight was based on studies in human and murine systems including transfer of FM-immunoglobulins to mice, that induced pain behaviour via effects on DRG.

It was found in Swedish, and replicated in Canadian cohort, that patients with high FM-Ab titers had higher pain intensity and more severe FM.

This discovery set the scene to propose a trial to target likely causative FM-Abs producing B cells with Rituximab (Rtx) in FM-Ab positive patients with severe pain (VAS≥50). An expected outcome is ≥30% pain reduction at week 16. Rtx is safe and well tolerated drug approved over 20-years ago for treatment of Ab or B-cell mediated diseases.

If treatment with Rtx proves to be effective, it would be the first DMT for FM. The ultimate benefit would be substantial.

We submitt this project proposal in order to prepare the team and all regulatory documents, and later conduct such a trial.