SAN DIEGO — A second or third course of treatment with rituximab was safe and effective in patients with active rheumatoid arthritis enrolled in an open-label extension study, according to two poster presentations at the annual meeting of the American College of Rheumatology.
The monoclonal antibody rituximab had previously been investigated in two phase II studies in rheumatoid arthritis, and patients who had demonstrated improvement in the first treatment course (C1) were eligible to enroll in the extension phase.
Thus far 192 have enrolled; 141 have received a second course (C2) of rituximab treatment, and 25 received a third course (C3), according to Dr. Paul Emery of the Leeds (England) General Infirmary.
During C1, patients received intravenous rituximab in a dosage of 500 mg or 1,000 mg on days 1 and 15, along with methotrexate, cyclophosphamide, or no disease-modifying antirheumatic drug. They also received corticosteroids or placebo.
During C2, patients received 1,000-mg rituximab on days 1 and 15, 10–25 mg/week of methotrexate, and intravenous glucocorticoid premedication; they also received oral glucocorticoids for two weeks. Responses at week 24 were compared with the C1 and C2 baselines.
In the poster that summarized the safety data from C2, Dr. Emery reported that the percentage of patients who experienced serious adverse events after C2 was similar to that after C1 (11% and 10%, respectively).
There was no evidence of cumulative toxicity with repeat courses of the drug, he noted.
Following C1, there was one serious infection (bacterial arthritis). Four patients experienced serious infections following C2—one each of appendicitis, otitis media, bronchopneumonia, and urinary tract infection.
There have been no reports of serious infections following C3, wrote Dr. Emery.
The majority of infusion-related adverse events were mild to moderate.
A separate poster presented efficacy data from the first 78 patients who have either been followed for 24 weeks following C2 or who withdrew from the trial.
“By all measures, rituximab retreatment following C2 was effective,” wrote Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas.
Disease Activity Score (DAS)-28 fell from a mean of 6.95 at C1 baseline to 4.58 at week 24, and then from a mean of 6.43 at C2 baseline to 4.16.
A total of 47 patients achieved ACR20 responses from the C2 baseline, and 57 achieved good to moderate EULAR responses.
C-reactive protein levels and rheumatoid factor titers both were significantly reduced during the observation periods after C1 and C2.
Rituximab targets CD20-positive B cells, and by binding CD20 it depletes B cells. However, because CD20 is not expressed on stem or plasma cells, B-cell recovery subsequently occurs.
Both B-cell depleted and B-cell recovered patients responded following C2, Dr. Fleischmann wrote.
Dr. Fleischmann disclosed that he has received research grants and consulting fees and is on the speakers' bureau of Genentech Inc.
Dr. Emery disclosed that he has received research grants and consulting fees from Roche.
There was no evidence of cumulative toxicity with repeated courses of rituximab. DR. EMERY