Canadian researchers report.
The findings endorse the endpoint used to define low disease activity in the study – Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 2 or less – as a meaningful treat-to-target outcome in SLE and also help to fill in missing information about the long-term longitudinal status of patients with recent-onset disease who enter either low disease activity or clinical remission status, first author Konstantinos Tselios, MD, PhD, and coauthors at the Centre for Prognosis Studies in the Rheumatic Diseases at the University Health Network’s Toronto Lupus Clinic, wrote in Arthritis Care & Research.
The concept of low disease activity (LDA) has emerged because it is rare for SLE patients to achieve sustained complete remission, the authors said. Existing studies on the outcomes of LDA and clinical remission have demonstrated comparable outcomes between the two in terms of damage accrual after 2 years, but they enrolled patients with prevalent disease, many of whom were in late stages.
“Given that disease duration has a significant impact on disease activity, the prevalence and characteristics of complete remission and LDA might have been affected,” they wrote.
The investigators therefore conducted the current study to assess damage accrual, medications used, flare rate, and mortality in inception patients who sustained complete remission and LDA status for 10 years.
The study involved 267 patients attending the University of Toronto Lupus Clinic who had at least 10 years of follow-up and no time interval between clinic visits exceeding 18 months. All patients fulfilled the revised American College of Rheumatology criteria for SLE classification or had three criteria and a supportive biopsy. The patients all had either LDA or clinical remission (SLEDAI-2K = 0, excluding serology) within the first 5 years since enrollment and maintained that status for 10 consecutive years, regardless of therapy.
A total of 10.1% of patients (n = 27) achieved prolonged clinical remission. Clinical manifestations at baseline included mucocutaneous disease in 70.4%, arthritis in 59.3%, cytopenias in 55.6%, nephritis in 25.9%, and central nervous involvement in 25.9%. Nephritis was class II in three patients, class III in one, and class IV in three.
For the 18% of patients (n = 48) who achieved sustained LDA, clinical manifestations included mucocutaneous disease in 81.3%, cytopenias in 66.7%, arthritis in 60.4%, serositis in 29.2%, nephritis in 22.9%, and central nervous system disease in 8.3%. The nephritis was class II in two patients, class III in four, class IV in two, and class VI in one. Patients in both groups were similar at baseline, but mean prednisone dose was higher in the remission group and more patients in the LDA group were taking antimalarials.
Time to remission and time to LDA were 1.2 years in both groups. After 10 years of follow-up, the mean SLEDAI was 1.2 in the remission group and 1.6 in the LDA group (P = .31) and 3.7 among patients not achieving either goal (n = 192; P less than .001).
Moreover, serology (complement C3/C4 and anti-double stranded DNA positivity) and antiextractable nuclear antigen antibody profile were similar in both groups.
No differences in flare rate or mortality emerged. Disease flares were observed in 25.9% of the remission group and 31.2% of the LDA group (P = .63) and flare rates were 0.038/patient-year and 0.065/patient-year, respectively (P = .23). Mortality after 10 years was 11.1% in the remission group and 10.4% in the LDA group (P = .93).
“Maintenance of this state could be an acceptable target for the long-term management of SLE. The concept of LDA is relatively new in SLE. Since complete remission has not been strictly defined yet and is rare, a more realistic target, such as LDA, may be of value in daily clinical practice as well as in clinical trials,” the investigators wrote.
The authors noted that the study was limited by the relatively low number of patients.
The University of Toronto Lupus Research Program is supported by the University Health Network, Lou & Marissa Rocca, and the Lupus Foundation of Ontario. The authors declared no potential conflicts of interests.
SOURCE: Tselios K et al. Arthritis Care Res. 2018 Jul 28. doi: 10.1002/acr.23720