The effects of treatment-target achievement on rate of subsequent flares in patients with systemic lupus erythematosus (SLE) were assessed in a study published in Lupus Science & Medicine. Overall, patients who achieved low disease activity or remission were much less likely to experience flares during follow-up than patients who did not reach treatment targets.
A single-center prospective study was conducted at Peking University First Hospital in Beijing, China. Adult patients with SLE with at least 2 visits to the hospital between January 2017 and December 2020 were eligible for study inclusion. Baseline and follow-up data were collected from electronic medical records. Low disease activity was defined using the lupus low disease activity status (LLDAS); remission was determined using the Definitions of Remission in SLE (DORIS); and disease flare was assessed using the Safety of Estrogen in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI Flare Index).
The Kaplan-Meier method was used to determine length of flare-free survival in patients with and without low disease activity or remission at baseline. Cox proportional hazard models were used to identify predictors of flare after achievement of LLDAS or clinical remission. The effects of glucocorticoid tapering and withdrawal were also studied.
A total of 185 patients were enrolled in the study, among whom 163 (88.1%) were women. Mean age at SLE onset was 33.5±14.9 years; median follow-up duration was 26.2 months.
Overall, 73 patients (39.5%) experienced a total of 95 flare episodes, of which 70 (73.7%) were of mild to moderate intensity and 25 (26.3%) were severe. Median time to first flare was 9.0 months from study enrollment.
According to Kaplan-Meier analyses, the cumulative flare rates at 6, 12, 24, and 36 months of follow-up were 11%, 23%, 46%, and 53%. Achievement of low disease activity or remission had a significant impact on flare risk. The incidence rates of flare were 0.18, 0.12, and 0.10 per patient-year after achieving LLDAS, LLDAS with a prednisone dose of 5 mg/day or lower, and clinical remission on treatment, respectively. Among patients who did not achieve LLDAS or remission, the flare incidence was much higher, at 0.49 per patient-year during follow-up.
Compared with patients who did not experience flares, patients with flares during follow-up were significantly younger at disease onset (30.7±12.4 vs 37.1±16.4 years; P =.01) and had lower C3 levels (726.7±209.0 vs 844.9±206.6 mg/L; P =.001).
Treatment withdrawal also had a marked effect on flare risk; patients who withdrew from receiving prednisone were much more likely to experience a flare compared with patients who continued to receive a low maintenance dose of prednisone (≤7.5 mg; hazard ratio [HR], 6.94; 95% CI, 1.86-25.86; P =.004). However, flare-free survival rates were comparable between prednisone maintenance regimens of 5 to 7.5 mg/day, 2.5 to 5 mg/day, and 0 to 2.5 mg/day, suggesting that an appropriate tapering plan does not increase risk for flare.
Results from this study identified potential predictors of flare in patients with SLE. Achievement of treatment targets appeared to have a protective effect, while low C3 levels were predictive of flare, regardless of prior remission.
Study limitations included the small cohort size and small number of patients who underwent treatment withdrawal, which limited statistical power.
“Achievement of treatment targets significantly lowered following flare rates and delayed the onset of flare,” the researchers wrote. “Future prospective studies with large sample sizes are expected to validate these findings.”
Hao Y, Ji L, Gao D, et al. Flare rates and factors determining flare occurrence in patients with systemic lupus erythematosus who achieved low disease activity or remission: results from a prospective cohort study. Lupus Sci Med. 2022;9(1):e000553. doi:10.1136/lupus-2021-000553