President YolaRX Consultants Rutgers The State University of New Jersey Montreal, Canada
Background: Patients with systemic lupus erythematosus (SLE) increases the risk of cardiovascular diseases1. While cardioprotective effects of first line SLE therapy have been demonstrated in real-life2,3, the impact of second line therapies on the long-term is very poorly documented.
Objectives: To assess the relative ratio of the occurrence of myocardial infarction (MI), stroke and embolism, as a composite cardiovascular outcome (CVO), in SLE patients, according to the use of individual second-line therapies.
Methods: A cohort of patients with SLE was followed in the French health care database (SNDS) from January 1, 2010, to December 31, 2020, which covers 99% of the population (>66 million persons). New drug users cohorts were identified systematically, including indicated second-line therapies [methotrexate (MTX); belimumab (BLM), azathioprine (AZA), and mycophenolic acid (MA)]. A sub-cohort of patients with a previous episode of SLE-related organ damage was also studied. A new treatment user was defined as no dispensing of the considered drug in the previous 360 days. For each new user, a patient without the considered drug was matched (1:1 ratio) on a high-dimensional propensity score using up-to 300 variables from 8 dimensions, age (±1 year), calendar date (±2 years), and time since SLE diagnosis. Conditional Poisson models were performed and adjusted for comorbidities and history of CVO.
Results: 52,883 patients with SLE were identified and followed on average 8.6 years. New use of AZA was observed in 2,743 patients and was associated with an adjusted rate ratio (aRR) of 0.48 (95% confidence interval (CI): [0.26-0.86] for CVO versus comparable non-users. Figures were respectively 7,819 MTX new-users associated with an aRR of 0.75 [0.55-1.02], 600 BLM new-users associated with an aRR of 0.41 [0.05-3.46] and 7,819 MA new users associated with an aRR of 0.54 [0.28-1.02]. Results were similar among the 17,295 patients with a prior SLE-related organ damage.
Conclusions: Indicated treatments of SLE show a protective effect on cardiovascular disorders with a long term follow up in real-life. The systematic new-users cohort design is an efficient method to assess effects of medications in real-life.
