SAN DIEGO – The combination of intravenous cyclophosphamide and rituximab shows promise for the reduction of lupus flares, both renal and nonrenal, in patients with severe systemic lupus erythematosus, according to Dr. Ali Shahzad.
Moreover, this benefit did not come at the cost of a significant increase in infections, as compared with intravenous cyclophosphamide monotherapy, Dr. Shahzad reported at the annual meeting of the American College of Rheumatology.
He reported on 43 patients with severe, recurrent SLE. Thirty-one were placed on intravenous cyclophosphamide monotherapy administered according to the National Institutes of Health standard protocol for the treatment of lupus nephritis. The other 12 got cyclophosphamide plus two 1,000-mg doses of rituximab (Rituxan) given 15 days apart. The combination regimen was given at the physician’s discretion for recalcitrant or recurrent flares of lupus nephritis in 10 of 12 cases, and for treatment-resistant CNS lupus or other extrarenal lupus in the other 2. Eight of the 12 recipients of combination therapy had previously been treated with intravenous cyclophosphamide, in most cases for lupus nephritis.
In the combination therapy group, the median duration of follow-up prior to dual therapy was 36 months, with an additional 21 months of follow-up after receiving the combination. Prior to combination therapy, these 12 patients collectively had 38 lupus flares, 26 of which featured renal involvement. In contrast, post treatment they developed just 13 flares, only 3 of which were renal, according to Dr. Shahzad of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md.
The 43 SLE patients had a total of 15 bacterial, 6 fungal, and 18 viral infections. And although there was a consistent trend toward higher rates in the combination therapy group, the differences fell far short of statistical significance.
Dr. Shahzad acknowledged the small sample size and retrospective design as important study limitations. However, based upon these encouraging, albeit preliminary, study findings, he and his NIH colleagues said they are planning a prospective clinical trial examining the efficacy and tolerability of the intravenous cyclophosphamide/rituximab combination in patients with severe, recurrent SLE.
Dr. Shahzad reported having no financial conflicts regarding this NIH-sponsored study.