To Örebro University

Background: Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding.

Objectives: To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities.

Methods: We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised.

Results: 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).

A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1.

Conclusion: To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity.