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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Jun 2003; 62(6): 534–539.
PMCID: PMC1754566

Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk

Abstract

Background: Systemic lupus erythematosus (SLE) is characterised by the presence of antibodies to double stranded DNA (dsDNA), which are involved in the pathogenesis of SLE. Previous studies showed that at least two thirds of patients develop a clinical relapse within six months after a significant rise in the anti-dsDNA level, and most relapses were prevented by the administration of corticosteroids at the time of the rise.

Objective: To determine whether mofetil mycophenolate (MMF) can prevent a clinical relapse without the side effects associated with corticosteroids.

Methods: 36 patients with SLE were examined monthly to determine whether a rise in anti-dsDNA level had occurred. A rise was defined as an increase of 25% of the level of the previous sample of at least 15 IU/ml within a four month period. After a rise patients were treated with MMF 2000 mg daily for six months. Patients were monitored monthly for the occurrence of a clinical relapse and to assess the serological activity and state of activation of CD4+, CD8+, and CD19+ lymphocyte subsets.

Results: Anti-dsDNA rose in 10 patients. Treatment with MMF was started in all these patients, and after six months no clinical relapse had occurred. Side effects were minimal. Antibodies to dsDNA decreased during the treatment (p<0.001), associated with a decrease in the state of activation of CD19+ lymphocytes. No changes were found in the state of activation of CD4+ or CD8+ lymphocyte subsets.

Conclusion: Administration of MMF after a rise in antibodies to dsDNA is well tolerated, decreases anti-dsDNA and B cell activation, and seems to prevent the occurrence of a clinical relapse in patients with SLE.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hahn BH. Antibodies to DNA. N Engl J Med. 1998 May 7;338(19):1359–1368. [PubMed]
  • ter Borg EJ, Horst G, Hummel EJ, Limburg PC, Kallenberg CG. Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum. 1990 May;33(5):634–643. [PubMed]
  • Bootsma H, Spronk P, Derksen R, de Boer G, Wolters-Dicke H, Hermans J, Limburg P, Gmelig-Meyling F, Kater L, Kallenberg C. Prevention of relapses in systemic lupus erythematosus. Lancet. 1995 Jun 24;345(8965):1595–1599. [PubMed]
  • Spronk PE, Horst G, Van Der Gun BT, Limburg PC, Kallenberg CG. Anti-dsDNA production coincides with concurrent B and T cell activation during development of active disease in systemic lupus erythematosus (SLE). Clin Exp Immunol. 1996 Jun;104(3):446–453. [PMC free article] [PubMed]
  • Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs. 1996 Feb;51(2):278–298. [PubMed]
  • Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, Lau CS, Wong AK, Tong MK, Chan KW, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000 Oct 19;343(16):1156–1162. [PubMed]
  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. [PubMed]
  • Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992 Jun;35(6):630–640. [PubMed]
  • Feltkamp TE, Kirkwood TB, Maini RN, Aarden LA. The first international standard for antibodies to double stranded DNA. Ann Rheum Dis. 1988 Sep;47(9):740–746. [PMC free article] [PubMed]
  • Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000 Aug;43(8):1801–1808. [PubMed]
  • Swaak AJ, Groenwold J, Bronsveld W. Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus. Ann Rheum Dis. 1986 May;45(5):359–366. [PMC free article] [PubMed]
  • Arbuckle MR, James JA, Kohlhase KF, Rubertone MV, Dennis GJ, Harley JB. Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus. Scand J Immunol. 2001 Jul-Aug;54(1-2):211–219. [PubMed]
  • Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991 Aug;34(8):937–944. [PubMed]
  • Walz LeBlanc BA, Gladman DD, Urowitz MB. Serologically active clinically quiescent systemic lupus erythematosus--predictors of clinical flares. J Rheumatol. 1994 Dec;21(12):2239–2241. [PubMed]
  • Esdaile JM, Abrahamowicz M, Joseph L, MacKenzie T, Li Y, Danoff D. Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail. Arthritis Rheum. 1996 Mar;39(3):370–378. [PubMed]
  • Ho A, Magder LS, Barr SG, Petri M. Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum. 2001 Oct;44(10):2342–2349. [PubMed]
  • Glicklich D, Acharya A. Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am J Kidney Dis. 1998 Aug;32(2):318–322. [PubMed]
  • Gaubitz M, Schorat A, Schotte H, Kern P, Domschke W. Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Lupus. 1999;8(9):731–736. [PubMed]
  • Heinschink A, Raab M, Daxecker H, Griesmacher A, Müller MM. In vitro effects of mycophenolic acid on cell cycle and activation of human lymphocytes. Clin Chim Acta. 2000 Oct;300(1-2):23–28. [PubMed]
  • Spronk PE, vd Gun BT, Limburg PC, Kallenberg CG. B cell activation in clinically quiescent systemic lupus erythematosus (SLE) is related to immunoglobulin levels, but not to levels of anti-dsDNA, nor to concurrent T cell activation. Clin Exp Immunol. 1993 Jul;93(1):39–44. [PMC free article] [PubMed]
  • Bijl M, van Lopik T, Limburg PC, Spronk PE, Jaegers SM, Aarden LA, Smeenk RJ, Kallenberg GG. Do elevated levels of serum-soluble fas contribute to the persistence of activated lymphocytes in systemic lupus erythematosus? J Autoimmun. 1998 Oct;11(5):457–463. [PubMed]

Figures and Tables

Figure 1
(A) SLEDAI score of 10 patients during a six month period of treatment with MMF after a significant rise in the level of antibodies to dsDNA. (B) VAS-Pa and (C) VAS-Ph represent the impression of the patient and the treating physician, respectively, ...
Figure 2
Levels of antibodies to dsDNA of each patient are shown from two months before the significant rise was established at t=0, until six months thereafter. MMF was started at t=0 and continued for six months (A). For each participant, levels of total IgG ...
Figure 3
Activation state of lymphocytes during six months of treatment with MMF. (A) Activation state of CD4+ lymphocytes depicted as the percentage of these cells staining positive for the activation marker CD25. (B) Activation state of CD8+ lymphocytes depicted ...

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