LEEDS, UK—Rheumatoid arthritis (RA) patients who are not candidates for tumor necrosis factor α (TNF) blockers might benefit from first-line treatment with rituximab (Rituxan^®, Genentech, Inc) researchers report in Rheumatology.¹

"This report suggests that rituximab is a very effective first-line biologic drug in clinical practice and can be safely given to patients who have relative contraindications for anti-TNF agents," conclude the researchers led by Dennis McGonagle, FRCPI, PhD, a professor of investigative rheumatology at the University of Leeds in the UK.

The new report studied 39 RA patients who had failed at least one traditional disease-modifying antirheumatic drug (DMARD) and who did not have access to TNF-blockers or could not tolerate them. Access to TNF inhibitors for treatment of RA is restricted by the National Health Service in the UK.

Patients were treated in a 'real world,' nonacademic environment. They received two rituximab infusions 2 weeks apart. Specifically, 17 patients received two 1000 mg doses, and 22 received the 500 mg dose.

Patients showed significant improvement in the Disease Activity Score-28 at 3, 6, 9, and 12 months. Moreover, the European League Against Rheumatism response criteria was observed in 29 of 33 patients (87.9%) at 3 months, 25 of 33 patients (75.8%) at 6 months, 22 of 29 patients (75.9%) at 9 months, and 23 of 30 patients (76.7%) at 12 months.

Patients also showed reductions in levels of C-reactive protein, rheumatoid factor and antinuclear antibody. Patients on the higher dose of the drug appeared to respond slightly better compared with their counterparts on the lower dose. Still, the authors point out, it is prudent to start with the lowest possible effective dose—500 mg every 2 weeks—because rituximab is a long-term treatment option for RA.

A safety edge?

The researchers point out that rituximab is likely at least as safe as anti-TNF agents, and there is no evidence of increased risk of serious infection. "Concerns have also been raised that the anti-TNF agents may be associated with an increased long-term risk of lymphoreticular malignancies including lymphomas, some of which rituximab is licensed to treat," the study authors conclude.

Some studies have linked repeated use of the drug to hypogammaglobulinemia, but so far this has been associated with infections.

Translating research into practice

"This is an interesting article," said Philip J. Mease, MD, with the department of internal medicine at the Swedish Medical Center and Rheumatology Associates in Seattle, Washington. "We will be eventually seeing much more large scale clinical trial data supporting the earlier use of rituximab," he told MSKreport.com. "So this message of allowing its consideration alongside anti-TNFs as a first-line agent is coming, [and] there is a similar push regarding abatacept currently. [But] whether physicians will change their current practice patterns is another matter."

Reference

1. McGonagle D, Tan AL, Madden J, et al. Rituximab use in everyday clinical practice as a first line biologic therapy for the treatment of DMARD-resistant rheumatoid arthritis. Rheumatology. 2008;47:856-867.