Long-Term Rates of SLE Flares After Clinical Remission

Retrospective data from a single center showed that 22.4% of patients with SLE will have a disease flare even after 3 years of remission. What are the implications for clinical follow-up?

Retrospective analysis of patient data from a single center in the United Kingdom found that 22.4% of patients with systemic lupus erythematosus (SLE) who were in remission for at least 3 years later developed disease flares. This data is significant since prior studies had limited long-term followup, so lupus flare rates occurring years after remission were not well-defined.  

In research published in Arthritis Care & Research, David Isenberg, MD, from the University College London, UK and colleagues retrospectively collected data from patients with SLE from a single center in the UK for a period of up to 32 years, aiming to examine rates of sustained clinical and serologic remission and to identify disease characteristics that were associated with remission.

For the purposes of this study, complete remission was defined as the absence of clinical SLE features for 3 years, as quantified by British Isles Lupus Assessment Group (BILAG) Index scores of C,D, or E.  Patients in remission also were no longer receiving steroids or immunosuppressants, with the exception of antimalarials, and had no serological evidence of double stranded DNA (dsDNA) antibodies, along with normal serum levels of complement C3. 

High Yield Data Summary

  • In a retrospective analysis of patients with SLE in the UK from a single center, lupus disease flares occurred even after 10 years of remission, thus researchers advocate for long-term followup of patients with SLE

Rates of patients who did not have clinical evidence of disease but had persistently positive anti-dsDNA or nucleosome antibodies, otherwise known as having serologically active clinically quiescent (SACQ) disease, were also examined.

Study participants fulfilled the revised American College of Rheumatology criteria for SLE and were primarily treated at University College Hospital in London for at >3 years between January 1978 until December 2010.  

Patients demographics recorded included sex, ethnicity, age at the time of SLE onset, duration of SLE, time to  remission, remission duration (if applicable), prior history of SLE flare, mucocutaneous, musculoskeletal, cardiopulmonary, renal, hematologic, or central nervous system involvement,  serological laboratory tests, and history of SLE pharmacotherapy.

Positivity for anti-dsDNA was defined by enzyme-linked immunosorbent assay results above the upper limit of normal (>50 IU) on 2 separate testing occasions. Serum C3 levels were measured by laser nephelometry.

A total of 532 patients met the study inclusion criteria.  In this group of patients, 344 (64.7%) did not achieve clinical and serologic remission within 3-years of followup. 

Seventy seven patients (14.5%) achieved remission as predefined by researchers. In 15 of these patients (22.4%), at lease one disease flare was noted.  When complete remission did occur, it was noted to occur within a median time of 9 years after first diagnosis. The median time of remission was 7 years. Twenty-three patients (4.3%) achieved complete remission for a minimum period of 10 years. 

Likelihood of achieving remission was decreased by renal (P<.001), neurologic (P=.002), and cardiopulmonary involvement (P<.001). No significant difference was found between likelihood of remission and presence of Sjögren syndrome (P=.230).

After 10 years of remission, 3 patients experience disease relapse. Sixty six patients (12.4%) were noted to achieve serologic remission, while 45 (8.5%) met criteria for SACQ. 

Causes of mortality in the 71 patient deaths identified in this study were infection (28.2%), cancer (23.9%), and atherosclerosis (12.7%), with a median age at death of 45 years. Four patients died in the complete remission group as compared to 61 deaths in patients did not achieve remission (P<.001).

This research further confirmed that patients who had increased probability of complete remission were older at the time of receiving their SLE diagnosis.

Summary and Clinical Applicability

Since lupus disease flares continue to occur after 10 years of remission, long-term followup of patients with SLE may be advised.

“We therefore emphasize the importance of continued close monitoring, because it is almost impossible to predict disease progression,” the authors advised.

Limitations and Disclosures

This study did not assess cumulative doses of corticosteroids and immunosuppressants and how they may possibly be associated with remission rates.  Cumulative SLE disease activity and organ damage were also not assessed.

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Medina-quiñones CV, Ramos-merino L, Ruiz-sada P, Isenberg D. Analysis of Complete Remission in Systemic Lupus Erythematosus Patients Over a 32-Year Period. Arthritis Care Res (Hoboken). 2016;68(7):981-7.