Correspondence

Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis

N Engl J Med 2001; 344:382-383February 1, 2001

Article

To the Editor:

There are several reasons for advocating caution in generalizing the beneficial findings reported by Chan et al. (Oct. 19 issue)1 to other patients with proliferative lupus glomerulonephritis. First, mycophenolate mofetil was compared with oral rather than pulsed intravenous cyclophosphamide, which has become the standard of treatment for patients with diffuse proliferative lupus nephritis.2

Second, patients with poor prognostic factors with respect to renal outcomes were either not included in the study or were underrepresented.3,4 In particular, patients with serum creatinine concentrations of more than 3.4 mg per deciliter (300 μmol per liter) were excluded, and many had only minor degrees of renal impairment. Only 3 of the 42 patients were men, presumably none were black, and there was little evidence of chronic renal parenchymal injury on biopsy. These base-line characteristics of the patients may well explain the higher rate of remission found in this study (79 percent, if only complete remission is taken into account) than in previous studies (46 percent).4,5

Third, the follow-up was short, considering that cyclophosphamide does not appear to provide any advantage over oral glucocorticoid therapy alone until the fifth year of follow-up.2 The fivefold higher rate of relapse in the mycophenolate mofetil group than that in a recent study of bolus doses of cyclophosphamide5 also arouses concern about the long-term efficacy of this treatment.

David A. Isenberg, M.D.
Fontini B. Karassa, M.D.
Royal Free and University College Medical School, London W1P 9PG, United Kingdom

5 References

1. 1

   Chan TM, Li FK, Tang CSO, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. N Engl J Med 2000;343:1156-1162
   Full Text | Web of Science | Medline

2. 2

   Austin HA III, Klippel JH, Balow JE, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-619
   Full Text | Web of Science | Medline

3. 3

   Austin HA III, Boumpas DT, Vaughan EM, Balow JE. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int 1994;45:544-550
   CrossRef | Web of Science | Medline

4. 4

   Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD. Factors predictive of outcome in severe lupus nephritis. Am J Kidney Dis 2000;35:904-914
   CrossRef | Web of Science | Medline

5. 5

   Gourley MF, Austin HA III, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis: a randomized, controlled trial. Ann Intern Med 1996;125:549-557
   Web of Science | Medline

Author/Editor Response

Dr. Chan replies:

To the Editor: The objective of our study was to examine the efficacy and tolerability of mycophenolate mofetil as compared with oral cyclophosphamide, each combined with prednisolone, in the treatment of patients with diffuse proliferative lupus nephritis. We studied only Chinese patients, and the size and duration of the study were not designed to examine the prevention of relapse. With regard to the control therapy, both pulsed intravenous cyclophosphamide and short-term oral cyclophosphamide have been used effectively in patients with diffuse proliferative lupus nephritis, and the data to date suggest that the risk of cyclophosphamide-related complications may be related more to the duration of treatment and the cumulative dose than to the route of administration.1-3

The severity of lupus nephritis in the patients we studied was evidenced by the histologic class, the activity score, and the clinical manifestations and was not defined by renal function alone. Patients with severe impairment of renal function were not included because we were interested primarily in determining whether the immunosuppressive treatments were effective in controlling immune-mediated acute inflammation. The favorable response to therapy in our study further affirms the importance of early and effective immunosuppressive treatment in achieving optimal outcome in patients with lupus nephritis. In this context, the importance of the induction of remission in ensuring a favorable long-term outcome was highlighted in a recent study.4 It is inappropriate to compare our study, which focused on the induction of remission, with others that examined the long-term deterioration of renal function.

Tak Mao Chan, M.D.
Queen Mary Hospital, Hong Kong, China

for the Hong Kong–Guangzhou Nephrology Study Group

4 References

1. 1

   Lewis EJ, Hunsicker LG, Lan S-P, Rohde RD, Lachin JM. A controlled trial of plasmapheresis therapy in severe lupus nephritis. N Engl J Med 1992;326:1373-1379
   Full Text | Web of Science | Medline

2. 2

   Cameron JS. Lupus nephritis. J Am Soc Nephrol 1999;10:413-424
   Web of Science | Medline

3. 3

   Chan TM, Li FK, Wong RWS, Wong KL, Chan KW, Cheng IKP. Sequential therapy for diffuse proliferative and membranous lupus nephritis: cyclophosphamide and prednisolone followed by azathioprine and prednisolone. Nephron 1995;71:321-327
   CrossRef | Medline

4. 4

   Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD. Factors predictive of outcome in severe lupus nephritis. Am J Kidney Dis 2000;35:904-914
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Juyoun Kim, Sang-Hyon Kim, Hae-Rim Kim, Sung-Hwan Park. (2010) Clinical Significance of Serum C1q-Circulating Immune Complexes in Patients with Lupus Nephritis. The Journal of the Korean Rheumatism Association 17:4, 393
   CrossRef

2. 2

   R. Birck. (2005) 15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis. Nephrology Dialysis Transplantation 21:1, 58-63
   CrossRef

3. 3

   Simin Goral, Christina Ynares, Scott B. Shappell, Shannon Snyder, Irene D. Feurer, Rumeyza Kazancioglu, Agnes B. Fogo, J. Harold Helderman. (2003) Recurrent lupus nephritis in renal transplant recipients revisited: It is not rare1. Transplantation 75:5, 651-656
   CrossRef

4. 4

   Kevin G. Moder. (2003) Mycophenolate mofetil: new applications for this immunosuppressant. Annals of Allergy, Asthma & Immunology 90:1, 15-20
   CrossRef

5. 5

   Bryan D. Gescuk, John C. Davis. (2002) Novel therapeutic agents for systemic lupus erythematosus. Current Opinion in Rheumatology 14:5, 515-521
   CrossRef

6. 6

   Daniel J. Wallace. (2002) Management of lupus erythematosus: recent insights. Current Opinion in Rheumatology 14:3, 212-219
   CrossRef

7. 7

   Robert W. McMurray, Valee Harisdangkul. (2002) Mycophenolate Mofetil:. The American Journal of the Medical Sciences 323:4, 194-196
   CrossRef