People with lupus who were treated with hydroxychloroquine (HCQ), an anti-malarial drug, early after a diagnosis of lupus had less cumulative organ damage at three years after diagnosis than those who did not receive HCQ, according to a new analysis.
Dynamics of Lupus within First Five Years of Diagnosis
Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort.
Urowitz MB, Gladman DD, Ibañez D, Fortin PR, Bae SC, Gordon C, Clarke A, Bernatsky S, Hanly JG, Isenberg D, Rahman A, Sanchez-Guerrero J, Wallace DJ, Ginzler E, Alarcón GS, Merrill JT, Bruce IN, Sturfelt G, Nived O, Steinsson K, Khamashta M, Petri M, Manzi S, Ramsey-Goldman R, Dooley MA, van Vollenhoven RF, Ramos M, Stoll T, Zoma A, Kalunian K, and Aranow C. (2012). Arthritis Care & Research (Hoboken) 64:132-7.
What is the topic?
Organ damage can accrue over time in people with lupus and is influenced by lupus disease activity, co-morbid conditions, and/or lupus treatments. The extent to which disease activity, organ damage, and autoantibody levels fluctuate over time early after lupus diagnosis have not been well-studied.
What did the researchers hope to learn?
The researchers hoped to learn about how lupus disease activity, organ damage, and autoantibodies fluctuate during the first five years after lupus diagnosis. In addition, they sought to determine any possible differences in these variables between Caucasians and non-Caucasians.
Who was studied?
A total of 298 people with lupus were included in the study. Patients were recruited to the study via their enrollment in the Systemic Lupus International Collaborating Clinics (SLICC) International Research registry of newly diagnosed lupus patients, which includes patients from 27 centers in 11 countries, including North America, Europe, and Asia.
How was the study conducted?
The patients described here were recruited to the study within 15 months of lupus diagnosis and were followed for at least five years. On an annual basis, these patients were assessed via a physical examination and laboratory tests, and were also assessed for lupus disease activity and organ damage via the SLE Disease Activity Index 2000 (SLEDAI-2k) and SLICC/ACR Damage Index (SDI), respectively. Organ damage was categorized as being either: a) related to use steroids, b) possibly related to use steroids, and c) independent of use of steroids. In addition, levels of each of the following were assessed for each patient during his/her annual visit: antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-cardiolipin antibodies (aCL), and lupus anticoagulant (LAC).
What did the researchers find?
Most of the patients included in the study were Caucasian women (some men were also included), but African-Americans, Asians, and Hispanics were also included. Upon entry to the study, the patients were an average age of 35 years old and had been diagnosed with lupus for about five months. Upon entry to the study, patients had mild-to-moderate lupus disease activity and only about 11% of patients had organ damage. About 44% of the patients who enrolled in the study without organ damage, developed such damage after five years of study follow-up.
For both Caucasians and non-Caucasians, lupus disease activity decreased to lower levels in the first year of diagnosis and remained at low levels for the next four years. However, when comparing this disease activity between Caucasians and non-Caucasians with lupus, the Caucasians had significantly lower levels of disease activity upon entry to the study and this pattern continued for the following five years. This difference was driven primarily by greater disease activity in Asians and Hispanics with lupus (both upon entry to the study and also over the five-year follow-up period).
Organ damage increased progressively over the five-year follow-up period, but did not differ significantly between Caucasians and non-Caucasians. Damage due to use of steroids increased while organ damage independent of steroid use remained constant over the five-year study period. Over that time period, the average steroid dose decreased but the average cumulative dose increased.
In terms of autoantibody levels, ANA positivity was high (94%) at study enrollment and increased by about 4% over the five-year follow-up period. Anti-dsDNA positivity was low (29%) at study enrollment but increased to 55% over the five-year follow-up period. Relatively few patients were evaluated annually for aCL and LAC, but the available data indicate that, over the five-year follow-up period, their positivity ranged from about 27% - 38% for the former and from about 20% - 52% for the latter.
What were the limitations of the study?
Based on the current study, it is unknown at what autoantibody level threshold (or even combinations of thresholds of different kinds of autoantibodies) organ damage begins to occur, and how this threshold might change (or could be modulated) over time (if at all). Also, whether such thresholds and their dynamics may differ according ethnicity could be important to learn about.
What do the results means for you?
The results suggest that organ damage in people with lupus may accumulate even over a time period during which lupus disease activity is well-controlled. It may be that, upon a new diagnosis of lupus, treatment regimens successfully keep disease activity low, but steroid treatments, in particular, may promote other non-lupus complications over time. The results also highlight that lupus patients from minority groups (particularly Asians and Hispanics) may experience greater disease activity, both upon lupus diagnosis and for five years afterward.
The findings highlight specific kinds of changes in lupus biomarkers that are most associated with effective use of belimumab in the treatment of lupus.