Purpose In this real‐world observational study, we analyzed the effects of different drugs on the quality of life (QoL) of patients with systemic lupus erythematosus (SLE). Method We identified patients in our prospective SLE Registry who received new medications. We measure QoL with MOS 36‐Item Short‐Form Health Survey (SF‐36), a generic health questionnaire, and SLEQOL, a disease‐specific instrument. We compared the patients' scores before and after initiation of treatment. Results We identified 259 episodes of drug initiation in 193 SLE patients. SLEQOL registered statistically significant changes with intravenous cyclophosphamide (total score and the domains of physical functioning, activities, and self‐image), mycophenolate (total score, treatment, mood, and self‐image) and azathioprine (total score, activities, and mood), but not with cyclosporin A and hydroxychloroquine. Two SF‐36 subscales (general health and physical functioning) showed statistically significant improvement in the patients who received intravenous cyclophosphamide. Both instruments have floor effect. There was weak correlation between changes in the QoL instruments and the patient assessment of disease activity or an objective disease activity index. Conclusion SLEQOL distinguishes the differential effects on QoL of the various drugs. Treatment with intravenous cyclophosphamide and mycophenolate impacted the highest numbers of domains of SLEQOL, followed by azathioprine, cyclosporin A, and hydroxychloroquine. SLEQOL may be a useful outcome measure in SLE clinical trials.
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