VERSAILLES, FRANCE — A small retrospective study found the monoclonal antibody rituximab benefited 7 of 11 French children with severe systemic lupus erythematosus.
The wide variation in regimens used at different French centers does not allow any firm conclusions to be drawn, investigator Marjolaine Willems, M.D., said in a presentation at the 12th European Pediatric Rheumatology Congress.
Dr. Willems of Hôpital de Bicêtre, Kremlin-Bicêtre, France, called for prospective trials to assess long-term safety and efficacy of rituximab in comparison with cyclophosphamide. “It needs to be investigated in future prospective studies,” she said.
The patients, all girls, were nearly 14 years old on average when they started rituximab treatment. Eight patients had class IV or V nephritis, and two had autoimmune cytopenia. One girl had hypoprothrombinemia, class II nephritis, and pulmonary hypertension.
Nine patients had a prior history of nephritis, and all were on immunosuppressive regimens previously. Two were also treated with cyclophosphamide. The average follow-up was 13 months.
Dr. Willems and her coauthors reported that 9 out of 12 courses of rituximab resulted in complete or partial remissions. Treatment failed in two patients, and was not tolerated in another.
Six of the eight patients with renal involvement achieved complete or partial remissions. Antiphosphoid antibodies became negative in three of four patients. Normalization of CD3 and/or CD4 was reported in four of eight patients.
Five children had mild side effects, such as rash, mild neutropenia, and benign infections. Five others had severe hematologic toxicity, including septicemia, thrombopenia, neutropenia, and lymphopenia.
B-cell depletion appeared to parallel clinical remissions but was not consistent in all patients, according to Dr. Willems. She advocated monitoring B-cell depletion in children treated with rituximab.
Issues that still need to be addressed in pediatric randomized trials include the optimal regimen of rituximab, cotreatment with cyclophosphamide, maintenance of immunosuppression, and long-term effects.
“We've got so much heterogeneity in the rituximab regimens and confounding factors that cannot lead us to a good conclusion,” she said in an interview.
The most that can be said is that “some patients who did not respond to cyclophosphamide alone had a good response with rituximab,” and some patients who had been taking maintenance therapies without rituximab had a relapse and then did well after adding rituximab to their maintenance therapy.