Pilot trial: No new safety issues or clinical benefit with Rituxan, atacicept combo for RA patients
Despite measurable biologic effects and no new safety issues, combination therapy with atacicept and Rituxan revealed no clinical benefits in patients with rheumatoid arthritis, according to recently published data.
Twenty-seven patients with moderate-to-severe rheumatoid arthritis (RA) were randomized to receive either two 1,000-mg infusions of Rituxan (rituximab; Genentech, Biogen Idec) 2 weeks apart and atacicept (Merck Serono) subcutaneous injections of 150 mg weekly (18 patients) or placebo for 25 weeks (nine patients). Patients were recruited from multiple European locations and had a disease duration of at least 12 months, responded previously to rituximab and showed residual disease activity. The minimum Disease Activity Score in 28 joints (DAS28) was greater than 3.2 at inclusion.
Twenty-six patients reported 295 mild or moderate adverse events (AEs) with a similar number of events between treatment groups. Three patients reported four serious AEs. Two of these patients were in the placebo group. Overall, the AEs included transient ischemic attack, ruptured cerebral aneurysm and drug hypersensitivity.
Total, mature and memory B cells were reduced to zero following treatment with rituximab. At week 64, mature B cell recovery was less than 10% in patients who received placebo and around 50% in patients who received atacicept. No differences were observed in the proportions of B cells between groups.
Atacicept was not associated with a decrease in C-reactive protein, while greater reductions in erythrocyte sedimentation rates were seen after week 12. Greater reductions in immunoglobulin (Ig) G, IgM and IgA at week 32 were seen in patients who received atacicept. No differences in the American College of Rheumatology response rates or DAS28 were observed between the treatment groups. – by Shirley Pulawski
Disclosure s : van Vollenhoven reports consulting fees from AbbVie, Biotest, Bristol-Myers Squibb, Crescendo Bioscience, GlaxoSmithKline, Janssen, Lilly, Merck Serono, Pfizer, Roche, UCB and Vertex (less than $10,000 each); and research grant support from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche and UCB. Please see the full study for a list of all other authors’ relevant financial disclosures.