Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis

Abstract

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.

Keywords

hydroxychloroquine membranous lupus nephritis mycophenolate mofetil

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References

Christiansen JV , Nielsen JP. Treatment of lupus erythematosus with mepacrine; results and relapses during a long observation . Br J Dermatol 1956; 68: 73-87 .

Rudnicki RD , Gresham GE , Rothfield NF. The efficacy of antimalarials in systemic lupus erythematosus . J Rheumatol 1975; 2: 323-330 .

The Canadian Hydroxychloroquine Study Group . A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus . N Engl J Med 1991; 324: 150-154 .

Fessler BJ , Alarcon GS , McGwin G Jr et al. ; LUMINA Study Group . Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual . Arthritis Rheum 2005; 52: 1473-1480 .

Tsakonas E , Joseph L , Esdaile JM et al. ; The Canadian Hydroxychloroquine Study Group . A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus . Lupus 1998; 7: 80-85 .

Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug . Semin Arthritis Rheum 1993; 23: 82-91 .

Leadbetter EA , Rifkin IR , Hohlbaum AM , Beaudette BC , Shlomchik MJ , Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors . Nature 2002; 416: 603-607 .

Means TK , Latz E , Hayashi F , Murali MR , Golenbock DT , Luster AD. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9 . J Clin Invest 2005; 115: 407-417 .

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271-1277 .

10.

Weening JJ , D’agati VD , Schwartz MM et al. The Classifcation of Glomerulonephritis in systemic lupus erythematosus revisited . J Am Soc Nephrol 2004; 15: 241-250 .

11.

Austin HA 3rd , Muenz LR , Joyce KM et al. Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome . Kidney Int 1984; 25: 689-695 .

12.

Racusen LC , Solez K , Colvin RB et al. The Banff 97 working classification of renal allograft pathology . Kidney Int 1999; 55: 713-723 .

13.

Petri M , Barr SG , Buyon J et al. RIFLE: Responder Index for Lupus Erythematosus . Arthritis Rheum 2000; 43: S244-S244 (abstract).

14.

Mok CC , Ying KY , Lau CS et al. Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial . Am J Kidney Dis 2004; 43: 269-276 .

15.

Petri M. Hydroxychloroquine prevents later damage in SLE . Arthritis Rheum 2001; 44: S280-S280 .