Patients who were in the clinical-remission-on-treatment category at any point in time—even for less than 25% of their follow-up—reduced their rates of organ damage by nearly half. Spending at least half of the time in the LLDAS category offered a comparable reduction in overall organ damage. Interestingly, this latter achievement offered protection only against certain kinds of damage, such as osteoporotic fractures, myocardial infarctions and musculoskeletal, central nervous system and renal damage. Strikingly, it did not prevent malignancies, cataracts, pulmonary fibrosis, pulmonary hypertension or cognitive impairment.
“I was surprised that LLDAS does not protect against all kinds of organ damage, such as malignancy and cognitive impairment. There is still so much to learn,” Dr. Petri says. “Pulmonary hypertension might be mediated by antiphospholipid antibodies rather than disease activity or prednisone.” The lack of an effect on pulmonary fibrosis, she adds, remains a puzzle.
“It is likely that different pathophysiological processes are behind the syndrome we call lupus, and these may lead to different long-term consequences,” Dr. van Vollenhoven says. One potential explanation for the findings, he says, is that the processes behind the specific consequences seen among the LLDAS patients hadn’t fully switched off.
Dr. Morand, though, cautioned against overanalyzing the differences in organ damage protection until they’ve been confirmed in other patient cohorts. “The prevalence of various adverse outcomes varies with race, age, gender and treatment, and we don’t know for sure if this finding will be reproduced,” he says. A reduction in cardiovascular damage, in particular, has been highly sought after for SLE patients. “It is likely to result in improved survival, but it is too early to make such a conclusion,” Dr. Morand says.
Like other studies, Dr. Petri’s clinical research found substantially more disease activity in African-American patients, and she stresses the importance of reporting results in different ethnicities because lupus is more severe in both African Americans and Hispanics. Yet her study also suggests that if they can achieve remission or LLDAS, African-American patients have reduced rates of organ damage as well, meaning the outcome category is valid in multiple ethnicities and, thus, generalizable.
Steroids Work—& Hurt
Given the role of corticosteroids in heightening the danger of long-term damage, the study may aid efforts to continue parsing the benefits and risks of low and moderate doses. Clinical remission on treatment, for example, allows up to 5 mg of prednisone per day, whereas LLDAS allows up to 7.5 mg. Dr. Petri says her research group previously found that a 6 mg daily dose of corticosteroids is the upper cutoff for avoiding organ damage: doses above that amount, she says, increase permanent organ damage by 50% or more.
