Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty‐Two–Week Randomized, Double‐Blind, Placebo‐Controlled Study

Abstract

ObjectiveTo assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).MethodsPatients with moderate‐to‐severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Secondary end points were reduction in the corticosteroid dosage and time to severe flare. Safety was assessed according to the adverse events (AEs) reported and the laboratory test results.ResultsOf 839 patients randomized, 836 (556 in the belimumab group and 280 in the placebo group) received treatment. A total of 159 patients withdrew before the end of the study. At entry, mean SELENA–SLEDAI scores were 10.5 in the belimumab group and 10.3 in the placebo group. More patients who received belimumab were SRI4 responders than those who received placebo (61.4% versus 48.4%; odds ratio [OR] 1.68 [95% confidence interval (95% CI) 1.25–2.25]; P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171.0 days versus 118.0 days; hazard ratio 0.51 [95% CI 0.35–0.74]; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40–52 (18.2% versus 11.9%; OR 1.65 [95% CI 0.95–2.84]; P = 0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported by 10.8% of patients taking belimumab and 15.7% of those taking placebo. A worsening of IgG hypoglobulinemia by ≥2 grades occurred in 0.9% of patients taking belimumab and 1.4% of those taking placebo.ConclusionIn patients with moderate‐to‐severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.

Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial

“…The SRI-6 response rate in the control subjects in this study (42.3%) was very high compared with prior SLE trials conducted in subjects with baseline SELENA-SLEDAI scores of ≥6 (20.4%,1 29.2%,3 27.0%4) or ≥8 (33.7%16). Analysis of SRI-6 was based on a logistic regression model with the following covariates fitted as explanatory variables: region, SELENA-SLEDAI at baseline (<=12, >12), UPCR at screening (<226, ≥226 mg/mmol), prednisone dose at baseline (<median dose, ≥median dose) and immunosuppressant use at baseline (yes, no).…”

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

“…Since its approval by the FDA, "real-world" clinical experience with belimumab has largely been positive [61][62][63]. Also since approval of belimumab as an IV drug, a randomized, double-blind, placebo-controlled trial of belimumab (200 mg fixed dose SC weekly through week 52) plus SOC in SLE demonstrated a statistically significantly greater response rate among belimumab-treated subjects than among placebo-treated subjects [64]. It is anticipated that the FDA will soon approve the SC formulation, thereby giving SLE patients the option of receiving their medication away from an infusion center or a medical clinic.…”

“…Of the eight late-stage clinical trials of BAFF antagonists in SLE reported to date in complete manuscript form, only four met their respective primary endpoints: each of the three phase-III trials of belimumab [57,58,64], and one of the two phase-III trials of tabalumab [69]. The phase-II belimumab trial, the phase-IIb blisibimod trial, the phase-II/III atacicept trial, and one of the two phase-III tabalumab trials all failed [67,70,72,73].…”

“…Moving forward (Table 1) 1) Unresolved issues (1) Responses in Black SLE patients Although the three phase-III belimumab trials in SLE met their primary endpoints, sub-group analyses failed to document a positive effect for belimumab among Black SLE patients [64,74]. (Clinical responses among in- dividual racial/ethnic sub-groups were not reported in the successful ILLUMINATE-2 trial [69]).…”

SAT0230 New oral anicoagulants in patients with antiphospholipid syndrome

“…OLE AEs were those occurring on or after the first OL dose. Efficacy evaluations were conducted, at reduced frequency, as per the DB phase1 . Results: Overall, 677 patients completed the DB phase, 662 entered the OLE; 625 completed.…”