Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus

Abstract

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.

Adverse Health-Related Quality of Life Outcome Despite Adequate Clinical Response to Treatment in Systemic Lupus Erythematosus

“…Interestingly, anti-dsDNA positivity at baseline was negatively associated with adverse outcome in physical HRQoL aspects and fatigue, as was anti-Sm positivity in mental HRQoL aspects and fatigue. Given the fact that more patients among responders had received belimumab rather than placebo (14,15), this finding is in line with what is known about serological activity at baseline portending favourable response to belimumab therapy in clinical (38)(39)(40) and HRQoL (41) facets.…”

EQ-5D-3L full health state discriminates between drug and placebo in clinical trials of systemic lupus erythematosus

“…Interestingly, higher proportions of FHS at week 52 were seen in anti-dsDNA-positive vs -negative patients who received belimumab 10 mg/kg plus ST, but no such difference was observed in patients who received ST alone, in conformity with the previously reported clinical and HRQoL benefit of belimumab in anti-dsDNA-positive individuals [ 44 ]. The same pattern was seen for anti-Sm-positive vs -negative patients, which aligns with previous reports of anti-Sm positivity predicting clinical benefit from B cell therapy with belimumab [ 45 ] or rituximab [ 46 ]. The apparent resemblance between the clinical benefit and the increased probability of experiencing FHS exerted by belimumab in anti-dsDNA- and anti-Sm- positive individuals consolidates the known-group validity of EQ-5D-3L FHS and further supports the notion that clinically relevant properties are incorporated in this PROM.…”

De novo lupus nephritis during treatment with belimumab

“…Accumulating evidence indicates that B cells exert regulatory properties through production of IL-10 [ 24 ]. Hence, our recent observation of decreasing serum IL-10 levels during BLM treatment [ 25 ] may be suggestive of a regulatory B cell downregulation, collectively warranting granular survey of BLM-mediated effects on the B cell repertoire.…”