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Prolonged Remission Now Possible in Lupus

— Less organ damage when remission is complete

Last Updated August 3, 2015
MedpageToday

More than one-third of patients with systemic lupus erythematosus (SLE) treated according to current standards were able to achieve prolonged remission, Italian investigators reported.

During 5 years of follow-up, 7.1% of patients achieved prolonged complete remission, meaning they had no clinical or serologic disease activity and were on no corticosteroids or immunosuppressive agents for the entire follow-up period, according to , and colleagues from the University of Padua.

Action Points

  • Note that this observational cohort study found that many patients with lupus are able to achieve remission, but few can do so without serologic evidence of disease.
  • Be aware that chronic, low-dose steroid use led to remission but was associated with steroid-related complications.

In addition, 14.7% had prolonged clinical remission off corticosteroids, which was defined as "serologically active but clinically quiescent," and 15.6% had prolonged clinical remission on prednisone in doses of 1 to 5 mg/day. In these two subgroups, immunosuppressants were allowed, and in all subgroups antimalarials were permitted for the prevention of relapse, the researchers reported online in

Most date from before 1990, at a time when diagnosis and treatment were very different than today. The lack of a current estimate on remission rates has been accompanied by an uncertainty as to how remission might influence long-term organ damage.

"Current evidence underlines that both persistent high disease activity and medication-related toxicity are associated with increased damage accrual, while the beneficial effect of achieving a disease remission on damage accrual has not been fully elucidated," Doria and colleagues wrote.

To produce a current estimate of remission rates, factors associated with failure to reach remission, and to assess the effects of remission on acquired organ damage, they analyzed data from their lupus cohort, which includes 224 patients who had been diagnosed with SLE after 1990.

The analysis included the years 2009 through 2013.

Participants' mean age was 38, disease duration averaged 11 years, and more than three-quarters were women. All were white.

Medications that had been used prior to remission included hydroxychloroquine, prednisone, azathioprine, mycophenolate mofetil (Cellcept), cyclosporin, methotrexate, and rituximab (Rituxan).

There were no differences in levels of remission reached according to age, sex, or disease duration.

A total of 62.5% of the cohort did not achieve prolonged remission, they noted.

In a univariate analysis, factors that were associated with an inability to reach remission included the presence of vasculitis, serositis, hematologic abnormalities, glomerulonephritis, and positive anti-double stranded DNA antibodies.

Also in the univariate analysis, a history of glomerulonephritis was less common in patients who reached complete remission than in those who were in clinical remission either off or on steroids (6.3% versus 42.4% and 48.6%).

On a multivariate analysis, these factors were associated with a failure to achieve persistent remission:

  • Vasculitis, OR 4.95 (95% CI 1.33-18.37, P=0.017)
  • Glomerulonephritis, OR 2.38 (95% CI 1.32-4.29, P=0.004)
  • Hematologic abnormalities, OR 2.19 (95% CI 1.17-4.12, P=0.014)

Organ damage was assessed at baseline and at the end of follow-up according to the Systemic Lupus International Collaborating Clinics/ACR Damage Index for SLE (SDI), and was categorized as being steroid-related or unrelated.

An increase in SDI occurred in 41.9% of patients, more often among patients who were not in remission.

Among patients who had achieved some level of remission, an increase in damage occurred more often in those having clinical remission but on corticosteroids (37.1%) than in those in clinical remission without steroids or in complete remission (18.4%, P=0.05).

Patients who remained on corticosteroids, even at low doses, also had more corticosteroid-related damage (P=0.039).

In a multivariate analysis, independent risk factors for damage were unremitted disease (OR 2.527, 95% CI 1.27-4.99, P=0.008) and previous use of high-dose intravenous corticosteroids (OR 2.35, 95% CI 1.10-5, P=0.026).

The authors noted that the optimal time of remission required to minimize damage and other adverse outcomes has not been determined.

"In our study, we defined remission as prolonged when lasting at least 5 consecutive years. Although we are aware that any length of 'prolonged' remission is arbitrary, we thought this cutoff was clinically significant, providing a considerable time interval for damage accrual," they wrote.

The observation that patients on low-dose steroids did accrue more damage over the 5-year period than those who were free of steroids highlights the importance of avoiding long-lasting exposure to corticosteroids in SLE. Minimal use of steroids should be considered a component of an overall treat-to-target strategy, they concluded.

A limitation of the study was the exclusion of minority patients, who can be at risk for more severe disease.

Disclosures

The authors reported no financial disclosures.

Primary Source

Annals of the Rheumatic Diseases

Zen M, et al "Prolonged remission in Caucasian patients with SLE: prevalence and outcomes" Ann Rheum Dis 2015; DOI: 10.1136/annrheumdis-2015-207347.