EULAR 2009: Retreatment With Rituximab for Rheumatoid Arthritis Achieves Response in Nonresponders

Alice Goodman

June 19, 2009

June 19, 2009 (Copenhagen, Denmark) — Patients with rheumatoid arthritis who fail to respond to a first treatment with rituximab can achieve a good response if retreated with the drug 6 months later, according to a preliminary study presented here at EULAR 2009: The Annual European Congress of Rheumatology.

"About one third of patients with rheumatoid arthritis fail to achieve an adequate response the first time they are treated with rituximab. We showed that retreating patients 6 months later can enhance clinical response to a level equal to [that acheived by patients] who fully responded to the first course of rituximab," said Edward Vital, MD, from the Leeds Institute of Molecular Medicine at the University of Leeds in the United Kingdom.

"This provides hope for patients who normally have limited options, because rituximab is typically given to patients after they fail other [disease-modifying antirheumatic drugs] and biological therapies," Dr. Vital said.

The rationale for the study was based on the observation that B-cell depletion is frequently incomplete after rituximab, as shown by flow cytometry, and predicts poor response. Patients with suboptimal responses might have disease potentially amenable to B-cell depletion with rituximab, Dr. Vital explained.

The single-center study focused on 104 patients with complete data who were treated with standard-dose rituximab (1 cycle of 1000 mg infusions given 2 weeks apart) for rheumatoid arthritis. Assessment with high-sensitivity flow cytometry showed that 90% of 37 nonresponders had incomplete B-cell depletion. Nonresponse was also predicted by higher baseline levels of memory B cells (P = .027) and progenitor plasma cells (=.006).

Twenty-five patients who failed to respond were retreated 6 months later with 1 cycle of rituximab. At 6 months, their B cells had not yet recovered to pretreatment levels, Dr. Vital explained.

A second course of rituximab achieved greater B-cell depletion, with 48% of patients achieving complete response (i.e., complete B-cell depletion on high-sensitivity flow cytometry; P = .02). Clinical response was observed in 72% patients, defined by EULAR criteria as a moderate or better response. A total of 32% had a good response and 16% were in remission. A significant improvement was seen in Disease Activity Score (DAS28) (P < .001) and its components.

"This study suggests that we can change our practice and that all patients who fail on rituximab can be retreated. Typically, when patients fail rituximab they are switched to another drug. We don't know if that is safe. With this approach, rituximab can be safely given 6 months apart," Dr. Vital explained.

"A Reasonable Option"

"Retreatment with rituximab is a reasonable option," said Roy Fleischmann, MD, clinical professor of medicine at the University of Texas in Dallas. "My impression is that most patients in the [United States] are switched to other drugs after suboptimal response to rituximab. The information in Dr. Vital's presentation is relatively new. As this knowledge becomes more widespread, it wouldn't be unreasonable to try a second course at 1000 mg."

Dr. Vital reports that Roche provided the study drug for 45 of the 104 patients in the trial, and has received speakers' honoraria from Roche. Dr. Fleischmann, who was not involved in this study, has received grant support and is a consultant for Pfizer.

EULAR 2009: The Annual European Congress of Rheumatology: Abstract 0P-0027. Presented June 11, 2009.

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