Pos1498 comorbidities and safety events in patients with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiorgan involvement. High disease activity may drive the development of comorbidities and safety events in SLE. Objectives To assess the prevalence of comorbidities and history of safety events at the time of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) assessment and the incidence of newly diagnosed comorbidities and safety events post-SLEDAI assessment among a prevalent cohort of adult SLE patients ≥18 years old. Methods This was a retrospective observational cohort study using the OM1 SLE Registry data from January 2013 to February 2022 (OM1, Inc., Boston, MA). The index date was defined as the first observed or estimated SLEDAI score with ≥12 months of prior data occurring after the first observed SLE diagnosis. The baseline period included all observed time prior to and including the index date. The follow-up period for identifying incident comorbidities and safety events included all available data after the index date. Incidence rates were stratified by disease activity. Results Among 10,837 patients, mean age was 52 years and 92% were female. The most common existing comorbidities were hypertension (44%), fibromyalgia (32%), anemia (29%), dyslipidemia (29%), thyroid disease (26%), obesity (25%), depression (22%), rheumatoid arthritis (22%), anxiety (19%), and Sjögren’s syndrome (18%). History of safety events at baseline most commonly included any infection (11%), abnormal liver function tests, hepatitis, or acute liver injury (ALI) (8%), elevated creatinine or acute kidney injury (AKI) (6%), and any malignancy (5%). Most patients were treated with first-line therapy for SLE (glucocorticoids and/or antimalarials) during follow-up (89%). Use of second-line (methotrexate, azathioprine, leflunomide) and third-line (belimumab, anifrolumab, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, voclosporin, rituximab) SLE therapies were less common (29% and 30%, respectively). During follow-up, 36% of patients had no disease activity, 28% had mild activity, 22% had moderate activity, and 14% had severe activity. Greater disease activity was associated with higher rates of incident hypertension, dyslipidemia, anxiety, thyroid disease, end-stage renal disease or dialysis, chronic liver disease/cirrhosis, avascular necrosis, seizures or epilepsy, and Sjögren’s syndrome. The most common incident safety events regardless of disease activity were any infection (30.7 per 1000 person-years [PY]), abnormal liver function tests, hepatitis, or ALI (20.3 per 1000 PY), and elevated creatinine or AKI (17.9 per 1000 PY). Correlation between incident safety events and disease activity varied by outcome. Conclusion Many common comorbidities occur more frequently among patients with higher SLE disease activity. The association between disease activity and the incidence of safety events was less clear. SLE-related systemic inflammation, comorbidities, and effects of SLE treatment (both positive and negative) likely contribute to patients’ risk profiles. Table 1. Incidence Rates per 1000 person-years Stratified by Index SLEDAI Score Comorbidity or Safety Event No Activity N=3,919 Mild N=3,022 Moderate N=2,413 Severe N=1,483 Hypertension 38.0 38.7 42.7 43.3 Dyslipidemia 31.8 32.0 34.3 35.7 Anxiety 26.9 30.9 32.3 38.5 Thyroid disease 23.6 24.3 27.2 29.0 End-stage renal disease or dialysis 3.2 3.6 3.6 5.3 Chronic liver disease 3.6 4.0 5.0 5.2 Avascular necrosis 2.5 2.9 3.4 4.4 Seizures or epilepsy 5.3 6.3 7.1 8.4 Sjögren’s syndrome 7.2 7.8 8.2 12.7 Abnormal liver function 16.3 22.4 25.4 19.2 Abnormal kidney function 14.4 20.9 20.3 18.0 Any infection 24.7 23 36.4 30.6 Major adverse cardiovascular events 8.1 9.2 6.3 6.6 Venous thromboembolism 2.3 4.4 4.0 4.6 Any malignancy 7.0 4.6 5.6 5.2 Disease activity cutoffs: No activity (SLEDAI=0), low (SLEDAI=1-5), moderate (SLEDAI=6-10), severe (SLEDAI=11+) Acknowledgements The authors would like to thank OM1, Inc. for providing the data and statistical analysis for this project. Financial support for the study was provided by AbbVie. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Disclosure of Interests Whitney Krueger Shareholder of: AbbVie, Employee of: AbbVie, Danielle Feger Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Thao Doan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D’Silva Shareholder of: AbbVie, Employee of: AbbVie.