Background/Purpose: Anti-malarial agents (AM) prevent damage in patients with systemic lupus erythematosus (SLE). We aimed to examine whether the duration of AM therapy early in the disease was associated with a reduced disease activity and the development of early damage in SLE.

Methods:   An inception cohort was identified from among SLE patients, followed prospectively in a single Clinic between 1970 and December 2015. We identified the patients who had a minimum of 5 years of follow-up after the diagnosis of SLE. Duration of AM therapy was based on the percentage of the time that the patients took the medication. They were divided into three groups: patients who took AM more than 60% of the time (group A), those who took AM for less than 60% of the time (group B), and those who did not receive AM (group C) during the 5 years of follow-up. We compared the demographic, disease activity, and treatment variables among the three groups. The outcomes were measured between the baseline and the 5-year follow-up. These outcomes included the change of SLICC/ACR damage index (SDI), flare event (defined by any increase of SLE disease activity index-2K (SLEDAI-2K) between 2 consecutive visits), low disease activity at year 5 (defined by a clinical SLEDAI-2K score of 1-2 regardless of serology), adjusted mean SLEDAI-2K over 5 years of follow-up, and AM related retinal toxicity. Regression analysis models were constructed to identify the predictors of the outcomes in multivariate models controlling for gender, age, disease duration, ethnicity, disease activity, and treatment.

Results:   A total of 459 patients were identified, 236 (51.4%) in group A, 88 (19.2%) in group B, and 135 (29.4%) in group C. At enrollment, gender, ethnicity, age, SLE duration, SLEDAI-2K and SDI were comparable in the three groups. The patients in group A had significantly lower cumulative dose of glucocorticoids (GC) compared to the patients in the other groups (P<0.001). Multivariate analysis revealed that the patients in group A had a lower risk of increasing SDI (relative risk = 0.71; 95% confidence interval (CI): 0.52, 0.95; P = 0.02) and were more likely to achieve low disease activity at year 5 (odd ratio = 1.96; 95% CI: 1.18, 3.26; P = 0.01) compared to the patients in group C. The patients taking AM more consistently had a lower cumulative dose of GC over the 5 years of follow-up (P<0.0001). There was only one patient with AM related retinal toxicity in each group.

Conclusion: Longer duration of anti-malarial therapy within the first 5 years of disease is associated with less disease activity and reduced risk of early progressive damage in patients with SLE.