Journal of Clinical Apheresis 7:153 (1992)
Plasmapheresis Therapy Is Ineffective in SLE Edmund J. Lewis and the Lupus Nephritis Collaborative Study Group Rush Presbyterian St. Luke’s Medical Center, Chicago
We have completed a randomized, controlled trial comparing a standard therapy protocol of prednisone and short-term (8 week) oral cyclophosphamide to a regimen encompassing standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 clinics. Severe lupus nephritis was defined according to WHO classification criteria. Patients underwent plasmapheresis 3 times weekly for 4 weeks. Drug therapy was standardized using strict adherence to 9 detailed medical management protocols. Baseline patient characteristics were age 32 t 13 years (SD); female 84%; white 63%; duration SLE symptoms 57 t 78 months; duration of nephritis 13 2 26 months; systolic BP 142 & 18; diastolic BP 88 t 13; serum creatinine 180 kMiL (1.9 mg/dl); 24 hour urine protein 5 . 3 g; anti-DNA 334 2 600 U x IO’iL; C3 0.40 0.18 g/L; C4 0.14 k 0.12 g/L; and cryoglobulins 180 t 260 mgiL. There were no significant differences in baseline characteristics between the 2 treatment groups. Forty-six patients received standard therapy and 40 patients received standard therapy plus plasmapheresis. The mean follow-up period was 136 weeks. Six patients ( 1 3%) in the standard therapy group died as compared to 8 (20%) in the plasmapheresis group. Eight patients (17%) in the standard therapy group developed renal failure as compared to 10 (25%) in the plasmapheresis group. Thirty patients (35%) reached stop points, 14 (30%) in the standard therapy group and 16 (40%) in the plasmapheresis group. There was no difference in the clinical course of patients in the 2 treatment groups, as measured by entry into clinical protocols. Twenty-seven patients in the standard group and 20 in the plasmapheresis group had an exacerbation during prednisone taper. The severity of
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0 1992 Wiley-Liss, Inc.
exacerbations was similar. A similar number of patients (40%) had an apparent remission, with a decrease in serum creatinine and of urine protein excretion to approximately normal. Patients treated with plasmapheresis had a significantly more rapid reduction of anti-ds DNA and cryoglobulin concentrations. An extended follow-up, carried out in January 1990, revealed no differences in clinical outcomes between the groups. The mean follow-up was 5.5 years: Deaths in the standard group totalled 10 (22%), renal failure in the standard group occurred in 12 patients (26%), and death or renal failure was 37%. In the plasmapheresis group there were 8 deaths (20%), 14 cases of renal failure (35%), and 18 patients died or had developed renal failure (45%). Retrospective analysis failed to reveal any predictive value for clinical parameters such as lupus serology, complement levels, or urine protein excretion. Histologic indices, such as the activity index or chronicity index, were not of value in predicting the ultimate occurrence of renal failure. The initial serum creatinine did, however, predict the renal outcome. The patients entering with a serum creatinine less that 1.2 mgidl had significantly less renal failure (6.5%) compared to those with a serum creatinine greater than 1.2 mgidl (29%). We conclude that plasmapheresis plus a standardized regimen of oral prednisone and short-term oral cyclophosphamide therapy did not improve the clinical outcome in patients with systemic lupus erythematosus with severe nephritis.
Address reprint requests to Edmund J . Lewis, M.D., Rush Presbyterian St. Luke’s Medical Center, Chicago, IL 60612.
Plasmapheresis Therapy Is Ineffective in SLE Edmund J. Lewis and the Lupus Nephritis Collaborative Study Group Rush Presbyterian St. Luke’s Medical Center, Chicago
We have completed a randomized, controlled trial comparing a standard therapy protocol of prednisone and short-term (8 week) oral cyclophosphamide to a regimen encompassing standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 clinics. Severe lupus nephritis was defined according to WHO classification criteria. Patients underwent plasmapheresis 3 times weekly for 4 weeks. Drug therapy was standardized using strict adherence to 9 detailed medical management protocols. Baseline patient characteristics were age 32 t 13 years (SD); female 84%; white 63%; duration SLE symptoms 57 t 78 months; duration of nephritis 13 2 26 months; systolic BP 142 & 18; diastolic BP 88 t 13; serum creatinine 180 kMiL (1.9 mg/dl); 24 hour urine protein 5 . 3 g; anti-DNA 334 2 600 U x IO’iL; C3 0.40 0.18 g/L; C4 0.14 k 0.12 g/L; and cryoglobulins 180 t 260 mgiL. There were no significant differences in baseline characteristics between the 2 treatment groups. Forty-six patients received standard therapy and 40 patients received standard therapy plus plasmapheresis. The mean follow-up period was 136 weeks. Six patients ( 1 3%) in the standard therapy group died as compared to 8 (20%) in the plasmapheresis group. Eight patients (17%) in the standard therapy group developed renal failure as compared to 10 (25%) in the plasmapheresis group. Thirty patients (35%) reached stop points, 14 (30%) in the standard therapy group and 16 (40%) in the plasmapheresis group. There was no difference in the clinical course of patients in the 2 treatment groups, as measured by entry into clinical protocols. Twenty-seven patients in the standard group and 20 in the plasmapheresis group had an exacerbation during prednisone taper. The severity of
*
0 1992 Wiley-Liss, Inc.
exacerbations was similar. A similar number of patients (40%) had an apparent remission, with a decrease in serum creatinine and of urine protein excretion to approximately normal. Patients treated with plasmapheresis had a significantly more rapid reduction of anti-ds DNA and cryoglobulin concentrations. An extended follow-up, carried out in January 1990, revealed no differences in clinical outcomes between the groups. The mean follow-up was 5.5 years: Deaths in the standard group totalled 10 (22%), renal failure in the standard group occurred in 12 patients (26%), and death or renal failure was 37%. In the plasmapheresis group there were 8 deaths (20%), 14 cases of renal failure (35%), and 18 patients died or had developed renal failure (45%). Retrospective analysis failed to reveal any predictive value for clinical parameters such as lupus serology, complement levels, or urine protein excretion. Histologic indices, such as the activity index or chronicity index, were not of value in predicting the ultimate occurrence of renal failure. The initial serum creatinine did, however, predict the renal outcome. The patients entering with a serum creatinine less that 1.2 mgidl had significantly less renal failure (6.5%) compared to those with a serum creatinine greater than 1.2 mgidl (29%). We conclude that plasmapheresis plus a standardized regimen of oral prednisone and short-term oral cyclophosphamide therapy did not improve the clinical outcome in patients with systemic lupus erythematosus with severe nephritis.
Address reprint requests to Edmund J . Lewis, M.D., Rush Presbyterian St. Luke’s Medical Center, Chicago, IL 60612.
