Background/Purpose: To update belimumab safety and efficacy data over 7 y in patients with active SLE. 

Methods: 449 SLE patients with SELENA-SLEDAI scores ≥4 were enrolled in a phase 2 study of belimumab 1, 4, or 10 mg/kg vs placebo, plus standard therapy, for 52 wk (NCT00071487). At wk 56, placebo patients switched to belimumab 10 mg/kg and belimumab-treated patients maintained their dose or switched to 10 mg/kg. From wk 80, all patients entering a continuation study received belimumab 10 mg/kg (NCT00583362). AEs were assessed at each study visit. Analyses of disease activity included SLE Responder Index (SRI; post-hoc analysis), British Isles Lupus Assessment Group (BILAG) A/B flares, SELENA-SLEDAI Flare Index (SFI), and biomarker changes. Efficacy assessments were limited to patients who were autoantibody positive (antinuclear antibody titer ≥1:80 or anti-double−stranded DNA ≥30 IU/mL) at baseline.

Results: Of the original 449 patients, 296 (66%) entered the continuation trial. At the end of 7 y, 190 patients remained. Total belimumab exposure was >1745 patient-y. Belimumab was well tolerated, with AEs/100 patient-y stable or decreasing over 7 y (see table). Seven patients died over 7 y; no cause predominated. Etiologies included aspiration pneumonia, infection, cardiovascular disease, suicide, osteomyelitis, and B-cell lymphoma. The SRI rate with belimumab was 46% at wk 52 (vs 29% with placebo; p <0.05), increasing to 55%–65.2% through the 7-y open-label treatment. The frequency of 1 new BILAG A or 2 new B flares with belimumab (all treatment arms combined) was 38% at 1 y (vs 44% with placebo), decreasing to 7.7% at 7 y. The frequency of all SFI flares was 84% (severe 17%) at 1 y (vs 85% [19%] with placebo), decreasing to 40.4% (2.1%) at 7 y. During the study, many patients with anti-double−stranded DNA at baseline became negative (45.8% at 7 y) and normalized complement (C3 66.0%; C4 71.4%). Of the 118 remaining patients on corticosteroids at baseline, corticosteroid use decreased (median reduction 55%; absolute reduction 3.7 mg/d at 7 y).

Conclusion: Belimumab plus standard SLE therapy was well tolerated in SLE patients for 7 y in an open-label study. Seven patients died; no cause predominated. Autoantibody-positive patients treated with belimumab had sustained improvement in disease activity and decreased flares over 7 y, accompanied by reductions in autoantibody levels and corticosteroid requirements.

 

AE Incidence (rate per 100 patient-y) in Patients Treated With Belimumaba
	Intervalb
	1 (0‒1 y)	2 (1‒2 y)	3 (2‒3 y)	4 (3‒4 y)	5 (4‒5 y)	6 (5‒6 y)	7(6-7y)
Patients, n (patient-y)	336 (320.1)	339 (299.1)	274 (258.1)	248 (234.2)	223 (215.8)	208 (197.6)	190 (167.0)
Overall AEs	326 (101.8)	322 (107.7)	260 (100.8)	237 (101.2)	211 (97.8)	191 (96.7)	172 (103.0)
Serious AEs	55 (17.2)	52 (17.4)	49 (19.0)	31 (13.2)	41 (19.0)	32 (16.2)	30 (18.0)
Overall infections	254     (79.4)	237 (79.2)	192 (74.4)	181 (77.3)	145 (67.2)	126 (63.8)	128 (76.6)
Serious infections	17 (5.3)	14 (4.7)	8 (3.1)	8 (3.4)	6 (2.8)	8 (4.0)	5 (3.0)
Malignanciesc	0	3 (1.0)	2 (0.8)	1 (0.4)	3 (1.4)	2 (1.0)	1 (0.6)
Mortality	3 (0.8)	0	1 (0.4)	1 (0.4)	0	0	2 (1.2)
aData presented as no. of patients with AE (no./100 patient-y) unless specified; binterval 1 includes only patients treated with belimumab (and not placebo) during the 52-wk, double-blind study (except mortality data includes 2 deaths during the 52-wk, double-blind period and 1 during the extension period); intervals 2–7 (and interval-1 mortality data; n = 424; 374.0 patient-y) include all belimumab-treated patients, including those originally randomized to placebo who subsequently switched to belimumab; cexcluding nonmelanoma skin cancer and including unspecified malignancy of lungs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sustained-disease-improvement-and-safety-profile-over-1745-patient-year-experience-7-years-with-belimumab-in-systemic-lupus-erythematosus-patients/