Abstract

Background:In patients with Systemic Lupus Erythematosus (SLE), Hydroxychloroquine (HCQ) treatment has been associated with reduced disease activity, lower rates of certain forms of organ damage, and improved survival1.Objectives:To gain insight into the mechanisms involved, we examined the impact of HCQ treatment on immunologic biomarkers that have been associated with higher rates of organ damage. These include lupus anticoagulant, anti-dsDNA, low complement, and anticardiolipins (aCL).Methods:We analyzed retrospective data on more than 56,000 quarterly clinic visits from more than 1000 patients in a large American clinical cohort of SLE patients. Patients visits were classified as “on HCQ” if they reported taking HCQ at that visit and at the previous visit. Patient visits were classified as “off HCQ” if they reported not taking HCQ at that visit and at the previous visit. For each patient, visits on and off HCQ were compared with respect to the rates of biomarker positivity. These comparisons were summarized across patients using using conditional logistic regression controlling for age.Results:Table 1 shows the results of our analyses. While on HCQ, the odds of being positive was significantly reduced for each biomarker: Lupus Anticoagulant (OR= 0.65), antidsDNA (OR=0.82), Low Complement (OR=.71), aCL IgG (OR=0.26), and aCL IgM (OR=0.45). However, there was a substantial difference between Caucasian Americans (CAs)and African Americans (AAs) with respect to the impact of HCQ. Notably, HCQ was associated with a 62% reduction in the odds of lupus anticoagulant among CAs, but no association was observed among AAs. In addition, HCQ was associated with a 34% reduction in antidsDNA among AAs, but no significant reduction among CAs.Table.Impact of treatment with HCQ on the odds of being positive for immunologic markersClinical markerAll Patients(n=951)Caucasian Americans(n=462)African Americans(n=409)Odds Ratio(95% CI)P-valueOdds Ratio(95% CI)P-valueOdds Ratio(95% CI)P-valueConfirmed Lupus Anticoagulant0.65(0.50, 0.85)0.00190.381(0.24, 0.58)<0.00011.051(0.69, 1.60)0.82antidsDNA (% positive)0.82(0.73, 0.91)0.00050.901(0.76, 1.06)0.190.661(0.56, 0.79)<0.0001Low complement0.71(0.64, 0.79)<0.00010.71(0.61, 0.83)<0.00010.73(0.62 0.86)<0.0001aCL IGG (% pos)30.26(0.17, 0.39)<0.00010.161(0.09, 0.30)<0.00010.531(0.27, 1.05)0.069aCL IGM (% pos)30.45(0.29, 0.68)0.00020.171(0.09, 0.32)<0.00012.451(1.09, 5.55)0.0321P-value for difference between Caucasian and African Americans < 0.0001.Conclusion:HCQ use was associated with a substantial decline in the rates of positive immunologic biomarkers in SLE patients. The different impact of HCQ in different races suggests the existence of racial differences in SLE subtypes and may indicate the need for different treatment strategies.

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