B-cell depletion using multiple infusions of Rituxan demonstrated no clinical benefit for patients with myalgic encephalomyelitis/chronic fatigue syndrome, according to data published in Annals of Internal Medicine.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is associated with greatly reduced quality of life,” Øystein Fluge, MD, PhD, from Haukeland University Hospital, Bergen, Norway, and colleagues wrote. “The socioeconomic costs are high, and elucidation of disease mechanisms, improvement in diagnostic approaches, and rational treatment are urgently needed.”
“Previous phase 2 trials indicated benefit from B-lymphocyte depletion,” they added.
Fluge and colleagues conducted a randomized, placebo-controlled, double-blind, multicenter trial to determine the effectiveness of Rituxan (rituximab; Genentech, Biogen) for the treatment of ME/CFS compared with placebo. The researchers enrolled 151 patients aged 18 to 65 years who had ME/CFS for 2 to 15 years.
Participants were randomly assigned to receive two infusions of rituximab at a dose of 500 mg/m² of body surface area, with a maximum dose of 1,000 mg, 2 weeks apart, then four maintenance infusions with a fixed dose of 500 mg at 3, 6, 9 and 12 months (n = 77) or placebo in the form of saline at equal volume (n = 74).
The researchers measured participants’ overall response rate, defined as a fatigue score of 4.5 or more for 8 or more consecutive weeks, and differences between treatment groups in repeated measurements of fatigue score over 2 years. They also measured secondary endpoints, including self-reported function over 2 years, components of the Short Form-36 Health Survey and Fatigue Severity Scale over 2 years and changes in these measures and physical activity level from baseline to 18 months.
In the placebo group, the overall response rate was 35.1%, compared with 26% in the rituximab group (difference, 9.2 percentage points; 95% CI, –5.5 to 23.3).
There was no difference in fatigue score through 2 years between treatment groups (difference in average score, 0.02; 95% CI, 0.27-0.31). Secondary outcomes also did not differ between treatment groups.
Serious adverse events were observed in 26% of patients in the rituximab group and 18.9% in the placebo group.
“This study highlights the importance of randomized and blinded clinical trials with a placebo group, especially in diseases that lack specific and sensitive biomarkers, have limited possibilities for objective end points, and rely mainly on self-reported symptom scores,” Fluge and colleagues concluded. “This trial did not show benefit from rituximab treatment in patients with ME/CFS.”
In an accompanying editorial, Peter C. Rowe, MD, from Johns Hopkins University School of Medicine, wrote that the study by Fluge and colleagues was methodologically sound.
He noted that the heterogeneity of ME/CFS is a significant challenge in performing research on the illness.
“The profound level of impaired function of affected individuals warrants a new commitment to hypothesis-driven clinical trials that incorporate and expand on the methodological sophistication of the rituximab trial,” Rowe concluded. – by Alaina Tedesco
Disclosures: Fluge reports receiving grants from the Kavli Trust, ME and You Foundation, Norwegian ME Association, Norwegian Regional Health Trusts and Norwegian Research Council. Please see study for all other authors’ relevant financial disclosures. Rowe reports receiving support from NIH and Solve ME/CFS.