NEW YORK — A combination of rituximab and cyclophosphamide offers significant long-term benefits to children with systemic lupus erythematosus, according to Dr. Thomas J.A. Lehman, who presented the results at a meeting sponsored by New York University.
“This combination is extremely effective, much more than either drug alone,” in the treatment of systemic lupus erythematosus (SLE), said Dr. Lehman, chief of the division of pediatric rheumatology at the Hospital for Special Surgery and professor of clinical pediatrics at Cornell University, both in New York.
SLE Disease Activity Index (SLEDAI) scores dropped from a mean of 9.79 before treatment to 1.43 after 12 months of treatment (P = .0009) for the group of 14 patients. C3 complement levels significantly increased (P = .0023), whereas the sedimentation rate fell (P = .0134). No changes were seen in hemoglobin levels or white blood cell levels.
Another marker of success was that patients were able to reduce their need for daily prednisone therapy. The mean daily dose fell by about two-thirds, from 33.3 mg/day to 11.96 mg/day after 12 months (P = .0004).
The protocol consists of a doublet of rituximab (750 mg/m
The doublet is repeated on days 14 and 15, and then the 2-week schedule is repeated at 6 and 18 months. These drugs have not been approved for the treatment of SLE in children.
Patients receive high-dose intravenous corticosteroids and intravenous diphenhydramine prior to rituximab infusion. Over the course of 3 years, most patients received at least three courses of therapy.
The group consisted of 11 females and 3 males who were about 12 years old when they were diagnosed with SLE.
Treatment with this protocol generally began 2 years after diagnosis, when the children were more than 14 years old. Five children were Asian, four children were Hispanic, three were white, and two were black. Six of the children had received prior cyclophosphamide monotherapy.
No serious adverse events were reported. Four patients had adverse events, including one each of urinary tract infection, herpes zoster, cellulitis, and lymphadenitis. All events resolved with treatment.
Four children were followed for at least 18 months after being diagnosed with biopsy-confirmed diffuse proliferative glomerular nephritis.
After undergoing the rituximab/cyclophosphamide treatment, all had normal complement levels and no indication of hematuria, proteinuria, or other urinary abnormalities and two of the four had negative antinuclear antibody (ANA) testing more than 1 year after treatment. “All these patients believe that they are cured,” says Dr. Lehman.
Dr. Lehman said that he is generally reluctant to discontinue prednisone, so all patients continue to receive approximately 10 mg/day of the drug. He reported that none of the children on prednisone showed signs of steroid toxicity such as depression, hirsutism, or Cushing's syndrome.
This protocol may not be appropriate for all children with SLE, according to Dr. Lehman. Not all children with SLE require aggressive therapy.
Data from studies done in the 1970s demonstrate that 30% of children with SLE do well with long-term, low-dose prednisone, whereas 30% develop steroid complications and 40% die or require dialysis, he said.
Aggressive therapy should be considered for children with persistent anemia (hemoglobin less than 10 g), persistent diastolic hypertension, pulmonary hypertension, or persistent hematuria (greater than 20 RBC/high-power field), or who have had recurrent emergency admissions for any reason.
The prevalence of SLE among children is estimated to be between 5 and 10 cases per 100,000 children. An estimated 8% of cases develop before children are 14 years of age, and about 15% develop before age 16.
Disclosures: The study received no commercial funding. Dr. Lehman is on the speakers bureau of Abbott Laboratories, Amgen Inc., and Pfizer Inc.
'This combination is extremely effective, much more than either drug alone' in the treatment of pediatric SLE.
Source DR. LEHMAN