These are not easy questions to answer for many reasons, including the lack of clear definitions and surrogate markers for low socioeconomic status, a lack of tools by which to measure such key factors as medication compliance, and the difficulties with performing long-term longitudinal studies in underserved populations. Early attempts to delineate the role of socioeconomic status argued against a significant role for race that was independent of socioeconomic factors, but were hampered by the inherent difficulties of undertaking these types of studies.
Perhaps the clearest picture of the respective roles of race and socioeconomic factors in lupus disease pathogenesis comes from the Lupus in Minorities Nature vs. Nurture (LUMINA) cohort studies. The LUMINA cohort consists of more than 600 patients from mixed ethnic and racial backgrounds who were recruited from sites in the southern United States, as well as Puerto Rico, beginning in the 1990s. These studies had several strengths: the use of robust assessment tools for measuring disease activity and damage accrual and the inclusion of multiple socioeconomic factors, such as income, education, home ownership and insurance status, as markers for poverty. Additionally, the cohort included a diverse patient population that included a sizable contingent of Hispanic patients—a group that was often underrepresented in previous lupus studies. Finally, patients were recruited relatively soon after diagnosis, allowing for a better assessment of the risk factors for worsening disease.
The LUMINA trials had several striking findings. At the time of diagnosis, race, ethnicity and genetic factors were strongly associated with organ involvement, but socioeconomic factors had less of an impact. Over time, however, these same markers for socioeconomic status gained increased significance with regard to disease progression over time, even when the initial disease severity was taken into account.7,8 Together, these findings suggest that there is likely a strong genetic component to the risk of developing lupus, as well as the risk of more severe disease. However, the risk of progression of organ involvement—particularly kidney involvement—over time is complicated by social factors as well. Other studies support this notion as well. Recent genetic studies, for example, point to African, Asian and Hispanic genetic ancestry as independent risk factors for the development of lupus nephritis, and long-term cohort studies have emphasized the role of poverty in disease progression over time.9,10
Reasons for Optimism
Although the gap between white lupus patients and black, Hispanic and Asian lupus patients remains significant, important strides have been made, particularly in treatment regimens for lupus nephritis. The introduction of mycophenolate mofetil (MMF) has proved a game-changer for black and Hispanic patients with severe renal involvement. In the Asperva Lupus Management Study (ALMS), which compared pulse dose cyclophosphamide to daily MMF, black and Hispanic patients had a significantly improved response to MMF compared with pulse dose cyclophosphamide.11 The response rates at six months were similar for both groups, with 54% of black patients achieving remission with MMF compared with 40% with cyclophosphamide, and 61% of Hispanic patients achieving remission with MMF vs. 39% with cyclophosphamide.
Lupus tends to occur at a younger age & tends to be more severe in non-white patients.
Undoubtedly, the ALMS trial was a significant breakthrough for treating black and Hispanic patients—although our optimism must be tempered by the fact that white and Asian patients in this trial were still much more likely to achieve remission overall. Furthermore, the subjects in the ALMS trial had relatively well-preserved renal function, and there remain few options for the treatment of severe lupus nephritis beyond IV cyclophosphamide.
