SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.

In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.

"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.

The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.

The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.

Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.

In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.

On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).

Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.

Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.

Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."

"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.

Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.

"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.

Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.

SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.

bjancin@frontlinemedcom.com

Antimalarials prove protective against long-term lupus damage