Case Study: Fall 2007 Lupus Now magazine
Lupus Nephritis Treated With Cyclophosphamide and Rituximab: A Case Study
by Thomas J.A. Lehman, M.D., Chief, Division of Pediatric Rheumatology, Hospital for Special Surgery, and Professor of Clinical Pediatrics, Weill Medical College of Cornell University, New York, and member of the LFA’s Medical-Scientific Advisory Council
Lupus nephritis with significant (class IV) kidney involvement often led to chronic renal failure in the past. In the 1980s, chemotherapy with cyclophosphamide was found to substantially improve the outcome for teenagers with lupus nephritis. While cyclophosphamide has been effective when used consistently, the protocol has required many doses over a three-year period. With the development of rituximab (a monoclonal antibody which removes activated B lymphocytes), there has been increased interest in combining the two drugs to improve the outcome and reduce the total amount of treatment needed.
Beth* is now 17. She came to me just after her 13th birthday complaining that she hurt all over. She’d been well until the previous summer when, after a long day at the beach, she complained of feeling sick. Over the next six weeks she began to run fevers and lose weight. Her pediatrician noted abnormal blood tests and then referred her to me. She was ANA-positive with a low white blood cell count, low platelet count, low complement levels, and both blood and protein in her urine. A renal biopsy showed she had diffuse proliferative glomerulonephritis (class IV renal disease).
We started Beth on 60 mg/day of prednisone, but there was no improvement; instead there was rapid worsening of her blood test and urine test results. The prednisone dosage was briefly raised to 100 mg/day, and cyclophosphamide and rituximab were given intravenously in the hospital. Two weeks later we gave her cyclophosphamide and rituximab again. She then received three monthly treatments with cyclophosphamide followed by two more courses of cyclophosphamide and rituximab. This is very aggressive therapy, but Beth had a very aggressive disease.
By the end of the six months of this aggressive therapy, Beth’s prednisone dosage was already down to 7.5 mg each day. Her urine was free of blood and protein, and her blood tests were normal, except for the positive ANA.
Six months later we again treated her with two doses of cyclophosphamide and rituximab. Since then she’s been taking only a low dosage of prednisone (5 mg/day) and her laboratory tests are all normal -- even her ANA is negative.
The combination of cyclophosphamide and rituximab is an exciting new therapy for people with lupus, and many doctors are now using it for adults as well as children with severe disease. Most doctors give the combination only when the patient is in trouble, and then wait to see what happens.
Using this combination of treatments aggressively, as we did in Beth’s case, we’ve been able to make some children’s lupus "disappear." Will their lupus come back again? We don’t know yet. Will this combination of cyclophosphamide and rituximab work for everyone? We don’t know that either. Is it perfectly safe? No, there will always be the risk of infection or other problems.
We still have to be careful, but we’ve made Beth and others like her dramatically better. Today Beth is living without steroid side effects and only wonders why she still has to come to the doctor. We know she still has to be watched carefully, but she feels like she’s cured.
The care of children with lupus has always involved a careful balance between doing everything possible to as-sure that they recover well, and avoiding side effects of the drugs as much as possible. The use of cyclophos-phamide and rituximab is a new combination therapy that aims to reduce side effects and improve the outcome of lupus. Although everyone receiving this therapy needs to be monitored carefully for possible side effects, and although the regimen has not yet completed controlled clinical trials, the early results have been extremely promising.
*Name has been changed.