Histologic Improvements Documented
Re-biopsy specimens reveal tissue effects of combination treatment
WASHINGTON, D.C.—The histologic changes that occur in patients with severe proliferative lupus nephritis following treatment with rituximab (Rituxan) plus cyclophosphamide may be seen, researchers say.
Swedish investigators conducted what they believe is the first rebiopsy study to look at immune cell markers and other changes following treatment with the combination therapy. The data from the study, presented here at the 2006 American College of Rheumatology annual meeting, suggests this combination therapy reduces lymphocyte markers CD3, CD4, and CD20 in the renal tissue in a majority of patients.
“Other researchers have reported that patients are improving when given these two agents but there has not been any repeat renal biopsy data until now,” said lead investigator Iva Gunnarsson, MD, a rheumatologist and consultant in the department of rheumatology at the Karolinska University Hospital in Stockholm, Sweden. “We are the first to show what happens histologically.”
Dr. Gunnarsson and her colleagues previously have presented data on the clinical efficacy of combined therapy with rituximab plus cyclophosphamide in 16 patients with severe, refractory systemic lupus erythematosus. The researchers analyzed renal biopsies performed in seven patients treated with rituximab (375 mg/m2 x 4) plus cyclophosphamide (500 mg/m2 x 2) as well as high-dose glucocorticoids. Pretreatment biopsies had been done and a re-biopsy was performed four to 12 months after initial treatment. Immunofluorescent staining was used to detect lymphocyte markers CD3, CD4, CD8, CD20, CD79a, and CD38.
During a follow-up, all seven patients had good clinical responses and showed signs of nephritic improvements. All patients had BILAG index score A for renal disease at baseline; after six months, three patients improved to B, three patients improved to C, and one patient improved to D. BILAG stands for British Islands Assessment Group, which developed the index.
Mean serum creatinine levels decreased from 88 to 73 µmol/L at six months and serum albumin increased from 27 to 34 g/L.
Prior to their initial treatment with these agents, the World Health Organization (WHO) renal histology category was III-B in two patients, IV-B in three patients, and IV-C in two patients. The mean histologic activity index was 6.4 and chronicity was 4.0. At re-biopsy (which occurred at a mean seven months after initial biopsy), the histology was WHO I-B in one patient, II-B in three patients, III-B in one patient, and V-B in two patients.
“All the patients improved histologically and clinically in terms of proteinuria and other signs and symptoms,” Dr. Gunnarsson said. “This is the first time we have had histopathological response data after rituximab treatment in patients with previous therapy-resistant proliferative lupus nephritis.”