Background: Belimumab is approved since 2011 for the treatment of systemic lupus erythematosus (SLE), a highly heterogeneous autoimmune disease. To aid personalised treatment approaches, it is important to quantify drug efficacy in specific disease manifestations.

Objectives: To determine the efficacy of belimumab in improving mucocutaneous (mc) manifestations of SLE and preventing mc flares in the five randomised controlled trials (RCTs) of belimumab which originally assessed belimumab efficacy in global SLE.

Methods: We designed a post-hoc analysis of 52-week data from five phase III RCTs of belimumab in adult SLE: four with intravenous (IV) belimumab (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-Northeast Asia (NEA), NCT01345253; and EMBRACE, NCT01632241), and one with subcutaneous belimumab (BLISS-SC, NCT01484496). We evaluated the efficacy of the approved dose of belimumab (10 mg/kg/month IV or 200 mg/week SC) vs placebo, both on top of non-biological standard therapy, in improving mc British Isles Lupus Assessment Group (BILAG) (considering patients with mcBILAG A or B at baseline; N=1839) and mc SLE Disease Activity Index 2000 (SLEDAI-2K) (considering all patients with baseline mcSLEDAI ≥2; N=2624) over time on intervention and in preventing BILAG-based mc flares (considering patients with mcBILAG B, C, D, or E at baseline; N=2954). We also observed the efficacy of belimumab in inducing sustained mcBILAG or mcSLEDAI-2K response, defined as improvement from baseline persisting for at least two consecutive visits 4 weeks apart and maintained through week 52. mcBILAG response was defined as a change in mcBILAG from A to B–D, or from B to C–D, whereas mcSLEDAI-2K response was defined as a ≥2-point reduction, both compared with baseline. Results are based on logistic (yielding ORs) or Cox (yielding HRs) regression analysis adjusting for trial variance.

Results: Patient characteristics did not differ between the treatment groups, including sex, age, ancestry, disease duration, SLEDAI-2K, PGA, anti-dsDNA antibody positivity, low C3 and/or C4, concomitant SLE medications, or glucocorticoid dose.

Regarding mcBILAG-based improvement, patients treated with belimumab benefited more than those on placebo, with significant separations from week 12 (week-52 OR: 1.29; 95% CI: 1.07–1.57; P=0.008). Notably, separations were more prominent in patients with positive levels of anti-dsDNA antibodies at baseline (week-52 OR: 1.44; 95% CI: 1.14–1.82; P=0.002) and patients with baseline SLEDAI-2K scores ≥10 (week-52 OR: 1.49; 95% CI: 1.18–1.89; P=0.001), but non-significant in the counter groups. Moreover, belimumab induced sustained mcBILAG-based improvement to a greater extent than placebo (HR: 1.23; 95% CI: 1.07–1.41; P=0.003), holding true for patients with positive levels of anti-dsDNA antibodies and SLEDAI-2K scores ≥10 at baseline, but not the counter groups. Regarding mcSLEDAI-2K-based improvement, patients treated with belimumab benefited more than those on placebo, with significant separations from week 16 (week-52 OR: 1.37; 95% CI: 1.16–1.62; P<0.001), holding true for patients with positive anti-dsDNA levels and patients with SLEDAI-2K ≥10 at baseline, but not the counter groups. Belimumab induced sustained mcSLEDAI-2K-based improvement to a greater extent than placebo (HR: 1.24; 95% CI: 1.17–1.31; P<0.001). Furthermore, belimumab prevented mcBILAG flares to a greater extent than placebo in patients with positive levels of anti-dsDNA antibodies at baseline (HR: 0.70; 95% CI: 0.50–0.98; P=0.035), as well as with a near-significant separation in patients with baseline SLEDAI-2K ≥10 (HR: 0.71; 95% CI: 0.51–1.00; P=0.05), but no separation was seen in the counter groups.

Conclusion: In this post-hoc analysis of five RCTs, belimumab is superior to placebo in inducing response and preventing flares in the mucocutaneous domain of SLE, especially in patients with high disease activity and serologically active disease at baseline.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Giorgia Grosso: None declared, Nefeli Giannopoulou: None declared, Alexander Tsoi: None declared, Nursen Çetrez: None declared, Dionysis Nikolopoulos: None declared, Julius Lindblom: None declared, Ioannis Parodis I have received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb, Elli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Otsuka, and Roche.