Higher Flare Risk Among Patients With SLE Receiving Maintenance Therapy

Among patients with systemic lupus erythematosus (SLE) attaining lupus low disease activity state (LLDAS), use of maintenance therapy is associated with increased risk for flares, according to results of a study published in Rheumatology.

Researchers from Centro Hospitalar Universitário de Coimbra (CHUC) Lupus Clinic in Portugal conducted a retrospective cohort study to evaluate risk factors for flares in patients with SLE fulfilling LLDAS.

Patients with SLE who had 2 or more visits between 2017 and 2020 were included in the study. Flares were defined using the Revised Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) Flare Index (r-SFI), SLE Disease Activity Score (SLE-DAS), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K).

A total of 292 patients with SLE, with a mean age of 46.2±14.5 years were included in the study; 87.3% were women and 96.9% were White. The mean SLE-DAS was 1.27±1.0 points.

The most common organ involvement was hematologic (79.8%), mucocutaneous (57.2%), arthritis (48.5%), and renal (36.0%), and the most common immunologic features were antinuclear antibodies (ANA; 100%), antidouble stranded DNA (90.4%), low complement (C)3/C4 (77.9%), and antiphospholipids (30.7%).

Overall, 28.4%, 24.7%, and 13.4% had at least 1 r-SFI, SLE-DAS, and SLEDAI-2K flares, respectively. The main manifestations of flares were arthritis (33.3%), rash (28.6%), lupus nephritis (27.0%), and cytopenia (12.7%). Flares led to treatment adjustment among 57.8% to 76.9%, according to flare definition.

In the multivariate analysis, predictors for r-SFI flares included hematologic cytopenia (hazard ratio [HR], 2.27; P =.022), use of immunosuppressants (HR, 1.97; P =.006), anti-U1-ribonucleoprotein antibodies (RNP; HR, 1.82; P =.017), use of prednisone (HR, 1.76; P =.025), and baseline SLE-DAS (HR, 1.40; P <.001).

Predictors for SLE-DAS flares were use of immunosuppressants (HR, 2.43; P <.001), anti-U1-RNP antibodies (HR, 2.16; P =.003), and baseline SLE-DAS (HR, 1.27; P =.017).

Flares according to SLEDAI-2K were associated with arthritis (HR, 2.43; P =.014), use of immunosuppressants (HR, 2.34; P =.0018), prednisone (HR, 2.04; P =.043), anti-U1-RNP antibodies (HR, 2.01; P =.048), and baseline SLE-DAS (HR, 1.48; P =.008).

However, patients with SLE in remission who did not receive glucocorticoids had a lower risk for SLE-DAS flares (HR, 0.60; 95% CI, 0.37-0.98).

A major limitation of the study that the widely used British Isles Lupus Assessment Group 2004 index (BILAG-2004) instrument was not used.

These data indicated that patients with SLE who required maintenance therapy were at higher risk for disease flare.

Study authors concluded, “[T]his study supports the view that SLE-DAS is a reliable and practical instrument to assess flares in clinical practice although further studies are needed to fully assess its validity as a flare tool.”