Previous antimalarial therapy in patients diagnosed with lupus nephritis: Influence on outcomes and survival

Abstract

The aim of this study was to analyze the effect of exposure to antimalarial drugs at diagnosis of lupus nephritis on the outcome of the disease, especially renal failure, comorbid processes, and survival. We analyzed a cohort of 206 consecutive patients with biopsy-proven lupus nephritis. Renal biopsies were categorized according to the classification proposed by the ISN/RPS in 2003. Exposure to antimalarial drugs (chloroquine and hydroxychloroquine) was defined as the use of these drugs before the diagnosis of lupus nephritis independent of dose and duration. Fifty-six (27%) patients had received antimalarials before the diagnosis of lupus nephritis. During the follow-up, these patients had a lower frequency of creatinine values >4 mg/dL (2% vs 11%, P = 0.029) and end-stage renal failure (2% vs 11%, P = 0.044) in comparison with those never treated with antimalarials. Patients exposed to antimalarials also had a lower frequency of hypertension (32% vs 50%, P = 0.027), infections (11% vs 29%, P = 0.006), and thrombotic events (5% vs 17%, P = 0.039). Twenty patients (10%) died during the study period. Patients exposed to antimalarials had a lower mortality rate at the end of the follow-up (2% vs 13% for those not exposed to antimalarials, P = 0.029). Multivariate analysis identified thrombosis and infections as statistically significant independent variables. Kaplan–Meier plots showed a lower rate of end-stage renal failure (log rank = 0.04) in patients exposed to antimalarials. In conclusion, exposure to antimalarials before the diagnosis of lupus nephritis was negatively associated with the development of renal failure, hypertension, thrombosis and infection, and with a better survival rate at the end of the follow-up. This, together with other published data, suggests that antimalarials should be considered a mandatory therapeutic option in all patients diagnosed with systemic lupus erythematosus.

Keywords

antimalarials cardiovascular disease hydroxychloroquine lupus nephropathy mortality systemic lupus erythematosus thrombosis

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References

1 D’Cruz DP Khamashta MA Hughes GR . Systemic lupus erythematosus. Lancet 2007; 369: 587 – 596 .

2 Mok CC; Ying KY; Ng WL; . Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am J Med 2006; 119: 355.e25–e33.

3 Huong DL Papo T Beaufils H . Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore) 1999; 78: 148 – 166 .

4 Petri M . Hydroxychloroquine use in the Baltimore Lupus Cohort: effects on lipids, glucose and thrombosis. Lupus 1996; 1: S16 – S22 .

5 Fessler BJ Alarcon GS McGwin G . Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum 2005; 52: 1473 – 1480 .

6 Ruiz-Irastorza G Egurbide MV Pijoan JI . Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006; 15: 577 – 583 .

7 Tan EM Cohen AS Fries J . The 1982 revised criteria for classification of SLE. Arthritis Rheum 1982; 25: 1271 – 1272 .

8 Weening JJ D’Agati VD Schwartz MM . International Society of Nephrology Working Group on the Classification of Lupus Nephritis, Renal Pathology Society Working Group on the Classification of Lupus Nephritis.

The classification of glomerulonephritis in systemic lupus erythematosus revisited.

Kidney Int 2004; 65: 521 – 530 .

9 Font J Cervera R Ramos-Casals M . Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center. Semin Arthritis Rheum 2004; 33: 217 – 230 .

10.

10 Alarcon GS McGwin G Bertoli AM . for the LUMINA Study Group.

Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L).

Ann Rheum Dis 2007; 66: 1168 – 1172 .

11.

11 Bosch X Guilabert A Pallares L . Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients. Lupus 2006; 15: 584 – 589 .

12.

12 Font J Ramos-Casals M Cervera R . Cardiovascular risk factors and the long-term outcome of lupus nephritis. QJM 2001; 94: 19 – 26 .

13.

13 Golbus J McCune WJ . Lupus nephritis: classification, prognosis, immunopathogenesis and treatment. Rheum Dis Clin North Am 1994; 20: 213 – 241 .

14.

14 Rudnicki RD Gresham GE Rothfield NF . The efficacy of antimalarials in systemic lupus erythematosus. J Rheumatol 1975; 2: 323 – 30 .

15.

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

16.

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

17.

17 Costedoat-Chalumeau N Amoura Z Hulot JS . Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum 2006; 54: 3284 – 90 .

18.

18 Lafyatis R York M Marshak-Rothstein A . Antimalarial agents: closing the gate on Toll-like receptors? Arthritis Rheum 2006; 54: 3068 – 3070 .

19.

19 Kasitanon N Fine DM Haas M Magder LS Petri M . Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis. Lupus 2006; 15: 366 – 370 .

20.

20 Tsakonas E Joseph L Esdaile JM . The Canadian Hydroxychloroquine Study Group.

A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus.

Lupus 1998; 7: 80 – 85 .

21.

21 Barber CE Geldenhuys L Hanly JG . Sustained remission of lupus nephritis. Lupus 2006; 15: 94 – 101 .

22.

22 Wallace DJ . Antimalarials: the ‘real’ advance in lupus. Lupus 2001; 10: 385 – 387 .

23.

23 Andrade RM Alarcon GS . Antimalarials in systemic lupus erythematosus: benefits beyond disease activity. Future Rheumatol 2006; 1: 225 – 233 .

24.

24 Bessant R Duncan R Ambler G . Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: A case–control study. Arthritis Rheum 2006; 55: 892 – 899 .

25.

25 Wasko MC Hubert HB Lingala VB . Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298: 187 – 193 .

26.

26 Tam LS Gladman DD Hallett DC Rahman P Urowitz MB . Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus. J Rheumatol 2000; 27: 2142 – 2145 .

27.

27 Sachet JC Borba EF Bonfa E Vinagre CG Silva VM Maranhao RC . Chloroquine increases low-density lipoprotein removal from plasma in systemic lupus patients. Lupus 2007; 16: 273 – 278 .

28.

28 Calvo-Alen J McGwin G Toloza S . LUMINA Study Group.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXIV. Cytotoxic treatment is an additional risk factor for the development of symptomatic osteonecrosis in lupus patients: results of a nested matched case–control study.

Ann Rheum Dis 2006; 65: 785 – 790 .

29.

29 Sotelo J Briceno E Lopez-Gonzalez MA . Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2006; 144: 337 – 343 .

30.

30 Ruiz-Irastorza G Ugarte A Egurbide MV . Antimalarials may influence the risk of malignancy in systemic lupus erythematosus. Ann Rheum Dis 2007; 66: 815 – 817 .

31.

31 Nived O Jonsen A Bengtsson AA Bengtsson C Sturfelt G . High predictive value of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for survival in systemic lupus erythematosus. J Rheumatol 2002; 29: 1398 – 1400 .

32.

32 Alarcón GS McGwin G Bastian HM . Systemic lupus erythematosus in three ethnic group VII: Predictors of early mortality in the LUMINA cohort. Arthritis Rheum 2001; 45: 191 – 202 .

33.

33 Urowitz MB Gladman DD . Contribution of observational cohort studies in systemic lupus erythematosus: the University of Toronto Lupus Clinic experience. Rheum Dis Clin N Am 2005; 31: 211 – 221 .

34.

34 Molad Y Gorshtein A Wysenbeek AJ . Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort. Lupus 2002; 11: 356 – 361 .

35.

35 Roman MJ Shanker BA Davis A . Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349: 2399 – 2406 .