Mar. 22, 2012

Long-Term Outcomes of Neuropsychiatric Lupus

Long-term outcome of early neuropsychiatric events due to active disease in systemic lupus erythematosus.
Wang M, Gladman DD, Ibanez D, and Urowitz MB. Arthritis Care & Research. 2012 Jan 30. doi: 10.1002/acr.21624. [Epub ahead of print].

What is the topic?

Neuropsychiatric manifestations in people with lupus, collectively referred to as neuropsychiatric lupus (NPSLE), are known to have a wide variety of short-term and long-term effects on health-related outcomes. Specifically, NPSLE events have been associated with increased organ damage, fatigue, unemployment, and lower health-related quality of life. In spite of this knowledge, the long-term effects of NPSLE events arising from active lupus have not been as thoroughly documented.

What did the researchers hope to learn?

The researchers hoped to learn about the effects of neuropsychiatric events attributable to active lupus, occurring around the time of lupus diagnosis, on long-term outcomes related to disease activity, organ damage, and health-related quality of life.

Who was studied?

Seventy-two people with lupus having at least one NPSLE event around the time of lupus diagnosis, as well as one-hundred forty-four lupus patients not having a NPSLE event around the time of lupus diagnosis, were studied.

How was the study conducted?

People with lupus followed every two to six months at the University of Toronto Lupus Clinic between 1970 and 2005 were included in the study. Lupus disease activity was assessed at each study visit by use of the SELDAI-2K, a validated measure. Organ damage was assessed annually by use of the SLICC/ACR Damage Index (SDI), a validated measure. Health-related quality of life was assessed annually by use of the Short Form-36 (SF-36), a self-reported measure.

NPSLE cases had at least one of the following neuropsychiatric events around the time of lupus diagnosis (hereafter called the “NPSLE group”): lupus headache, cerebrovascular disease-related event, organic brain syndrome, cranial nerve disorder, visual disturbance, seizure, or psychosis. For purposes of comparison, people with lupus not having a NPSLE event around the time of lupus diagnosis (hereafter called the “non-NPSLE group”) were also included. These control cases were matched according to age, sex, disease duration, and decade at first clinic visit.

What did the researchers find?

Most of the people included in the study were women who were an average age of 34 years old and had an average disease duration of about three months. Almost half of them had been diagnosed with lupus since the year 2000, and fewer were diagnosed in the 1970s, 1980s, and 1990s in relatively equal proportions. The NPSLE cases included the following: lupus headache (15%), seizures (15%), visual disturbances (11%), cerebrovascular disease-related event (10%), organic brain syndrome (10%), psychosis (10%), and cranial nerve disorder (4%).

People in the NPSLE group showed significantly greater overall lupus disease activity at the first study visit as compared to those in the non-NPSLE group. However, when NPSLE-related disease activity was excluded from this analysis, there were no significant differences in overall lupus disease activity between groups. At the first study visit, there were no significant differences in organ damage between groups (regardless of whether NPSLE-related events were included or not). At the first study visit, people in the NPSLE group had significant impairments in physical, but not mental, health-related quality of life as compared to people in the non-NPSLE group.

When considering long-term outcomes at years 1, 3, and 5 after the initial study visit, there were no significant differences between groups in terms of overall disease activity or (physical or mental) health-related quality of life (regardless of whether NPSLE events were included or not). The only long-term significant difference that emerged was that people in the NPSLE group had greater organ damage (but only when NPSLE events were included) at the 1-year (but not the 3- or 5-year) follow-up.

What were the limitations of the study?

This study included a relatively low number of NPSLE patients, which may have affected the ability to find statistical differences between groups in some cases (especially for quality of life measurements, which only begun to be implemented at this lupus clinic in the 1990s). In addition, NPSLE events were defined in this study according to the SLEDAI-2k, which does not include all of the NPSLE events described in people with lupus by the American College of Rheumatology. The exclusion of some NPSLE events may also have affected the ability to find statistical differences between groups. Lastly, the time it took for early NPSLE events to resolve or the nature of their outcomes were not compared between the NPSLE and non-NPSLE groups.

What do the results mean for you?

The results suggest that early NPSLE events due to active lupus do not appear to significantly contribute to long-term health-related outcomes, including effects on disease activity, other organ damage, and quality of life. However, for the reasons mentioned above, these findings should be interpreted with caution.

This study found that people in the NPSLE group entered the study with significantly greater disease activity, but this effect was not present 1, 3, or 5 years later. However, additional analyses revealed that despite not having increased disease activity after initial study entry, people in the NPSLE group tended to have recurrences of NSPLE events for up to three years after study entry. In addition, people in the NPSLE group entered the study with organ damage comparable to that found in the non-NPSLE group, but organ damage in the NSPLE group was significantly greater one year later. Furthermore, although health-related quality of life did not significantly differ between the NPSLE and non-NSPLE groups, this may have been due to insufficient data to find such differences. Indeed, previous studies have consistently reported lower quality of life in NPSLE patients.

Overall, the findings suggest that people in the NPSLE group accumulate organ damage more rapidly than those in the non-NPSLE group. This organ damage, however, appears to stabilize over time to comparable levels between NPSLE and non-NPSLE patients. In addition, reduced health-related quality of life tends to be persistent in both NPSLE and non-NPSLE patients. Lastly, this study suggests that NPSLE-related disease activity may occur in greater isolation than other kinds of lupus complications.


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