EXTENDED REPORT

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

M Bijl¹, G Horst¹, H Bootsma², P C Limburg³, C G M Kallenberg¹

¹ Department of Clinical Immunology, University Hospital, Groningen, The Netherlands
² Department of Rheumatology, University Hospital, Groningen, The Netherlands
³ Department of Pathology and Laboratory Medicine, University Hospital, Groningen, The Netherlands

Correspondence to:
Correspondence to:
Dr M Bijl, Department of Internal Medicine, Division of Clinical Immunology, University Hospital, PO Box 30.001, 9700 RB Groningen, The Netherlands;
m.bijl{at}int.azg.nl

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.

Keywords: systemic lupus erythematosus; anti-dsDNA antibodies; treatment; mofetil mycophenolate

Abbreviations: dsDNA, double stranded DNA; FITC, fluorescein isothiocyanate; IMPDH, inosine 5'-monophosphate dehydrogenase; MMF, mycophenolate mofetil; PE, phycoerythrin; SLE, systemic lupus erythematosus; SLEDAI, SLE disease activity index; VAS-Pa, visual analogue score of the patient; VAS-Ph, visual analogue score of the treating physician

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