COPENHAGEN — Rheumatoid arthritis patients who do not respond to initial treatment with rituximab can be re-treated successfully with a second course of the B-cell-depleting, monoclonal anti-CD20 antibody after 6 months, Dr. Edward Vital reported at the European Congress of Rheumatology.
The findings are particularly important because rituximab is often used as a treatment of last resort after the failure of other therapies, such as anti-tumor necrosis factor agents and methotrexate, “and approximately one-third of patients fail to achieve an adequate response to initial treatment with the drug,” said Dr. Vital of the Leeds Institute of Molecular Medicine at the University of Leeds (England).
Although it had previously been presumed that RA patients who failed initial rituximab therapy had B-cell-independent disease, the new data suggest that is not the case, said Dr. Vital.
To determine whether nonresponders to initial rituximab therapy might have disease that is potentially still amenable to B-cell-depletion therapy, and to assess the impact of re-treatment, Dr. Vital and his colleagues assessed the B-cell status and treatment response of 104 RA patients treated with standard doses of rituximab. All of the patients were positive for rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies. Of the 104 patients, 38 did not respond to initial therapy, based on change in clinical status as measured by Disease Activity Score 28 and EULAR criteria.
A comparison of baseline blood and synovial B-cell parameters showed no difference in erythrocyte sedimentation rates or C reactive protein levels between nonresponders and responders. But nonresponders had significantly higher numbers of memory and pre-plasma cells at baseline, along with more synovial B cells, Dr. Vital reported. Additionally, using highly sensitive rare-event fluorescence-activated cell sorting (RE-FACS), the investigators identified incomplete B-cell depletion in 90% of the treatment nonresponders, he said.
Of the nonresponders, 25 underwent re-treatment 6 months later, “when their B-cell numbers were significantly lower than they were at baseline of their first treatment cycle,” Dr. Vital reported. Among the re-treated patients, 72% responded clinically (defined as a moderate or better EULAR response) to the therapy at 6 months. Of these, 32% had a good response and 16% were in remission—response rates that are comparable to those observed among treatment-naive patients, he said.
The findings have had an immediate impact on clinical practice at the Leeds Teaching Hospitals. “From these results, we have immediately changed our practice regarding how we treat these patients. Now all patients who fail the first cycle of rituximab get a second cycle of treatment,” Dr. Vital said.
“The next question to consider is whether patients who have predictors of poor response could be treated more intensively from the outset, possibly with a different dose of rituximab, which is something we are currently investigating,” he noted. Dr. Vital disclosed a financial relationship with Roche, which provided free study drugs for 45 patients. The study was funded by the U.K. National Institute for Health Research.
To watch an interview of Dr. Vital, go to www.youtube.com/watch?v=YfEX2UxSlps