Background/Purpose: To determine whether degree of response among responders to subcutaneous (SC) belimumab (BEL) + standard of care (SoC) is greater than that for responders to placebo (PBO) + SoC.

Methods: Patients with SELENA-SLEDAI (SS) ≥8 on stable SoC ≥30 days were randomized (2:1) to weekly SC BEL 200 mg + SoC or PBO + SoC in BLISS-SC (NCT01484496). Primary endpoint was SLE Responder Index 4 (SRI4) at week (Wk) 52 (≥4-point SS reduction, <0.3 increase in Physician’s Global Assessment [PGA], and 0 new BILAG A or ≤1 new BILAG B organ domain scores, all vs baseline [BL]). SRI4 responders were compared based on treatment (BEL vs PBO) for changes in clinical and laboratory parameters. SRI4 non-responders were also evaluated.

Results: 61.4% of BEL + SoC and 48.4% of PBO + SoC were SRI4 responders¹. BEL + SoC responders had better outcomes than PBO + SoC responders at Wk 52 (Table 1) and during the trial: greater % reductions in SS (Wk 20-52, p≤0.0199) and PGA scores (Wk 20-52, p≤0.0304); organ system improvement (SS Wk 52 immunologic [p=0.0064] and vascular [p=0.0199] and BILAG vasculitis [Wk 16-52, p≤0.0301]); 65% reduced risk of severe flare (HR=0.35 [95% CI: 0.13, 0.94], p=0.0367); normalized complement levels (Wk 16-20,28-36, 44, 52: C3 p≤0.0232 and Wk 16-24, 36-52: C4 p≤0.0303). Percent of patients with ≥ 5, 6, 7, or 8 point reductions in SS excluding serology (anti-dsDNA, complement) were numerically greater for BEL + SoC responders from Wk 8-52, with significant differences at earlier timepoints (Table 2). Among patients receiving BL prednisone >7.5 mg/day, more BEL + SoC responders reduced their CS dose ≥25% to ≤7.5 mg/day during Wks 40-52 vs PBO + SoC responders but did not reach statistical significance (23.8% vs 14.6%, OR 1.79 [95% CI: 0.89, 3.59], p=0.1008). Anti-dsDNA shifts and FACIT-fatigue score improvements were similar between groups. Non-responders had no significant differences, irrespective of treatment, in changes in SS (± serology) or PGA, organ system involvement, flares, steroid use, complement, anti-dsDNA, or FACIT-fatigue scores. BL BAFF levels (range 1.574-1.769 ng/mL) and SoC medications were similar across treatment groups regardless of SRI4 response. No gender differences were noted.

Conclusion: SRI4 responders with BEL + SoC had greater degree of response compared to PBO + SoC based on clinical and serological measures. Earlier SS reductions (± serology) for BEL + SoC responders points to more rapid clinical improvement. These observations add robustness to existing knowledge that treatment with BEL could add therapeutic benefit to SoC alone.

Reference – 1. Arth Rheum 2017;69:1016-27.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/not-all-clinical-responders-in-sle-are-equal-comparison-of-subcutaneous-belimumab-standard-of-care-responders-to-placebo-standard-of-care-responders/