Background/Purpose

B cells have a central role in Systemic Lupus Erythematosus (SLE) and autoantibody production. B-Lymphocyte Stimulator (BLyS) is important for the activation and maintenance of B cells. Belimumab is a recombinant monoclonal antibody that specifically binds to soluble BLyS, and the only biologic agent approved for treatment of SLE. Its effects in patients with lupus nephritis (LN) are poorly known.

The aim of this study was to investigate the effects of belimumab given as an add-on to patients with active SLE despite standard-of-care therapy, with focus on patients with renal involvement.

Methods

Twenty-three patients (mean age 39.5 years) have been treated with belimumab at Karolinska University Hospital and have been included in this prospective observational study. Clinical data were acquired at baseline and at week 12, 26, 52 and 104. Disease activity was assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM). C3 and C4 levels were determined by nephelometry. The predominant organ manifestations to motivate treatment with belimumab were mucocutaneous (n=14) and muskuloskeletal (n=14). Thirteen patients with history of LN, five of them having signs for nephritis and low-grade proteinuria, were included.

Results

At baseline, all but 2 patients received oral prednisolone (mean dose 9.1 mg/d, range 0–20 mg/d), 17 patients received antimalarials, 6 received azathioprine, 4 mycophenolate mofetil, 1 methotrexate, and 1 cyclosporine. The median SLEDAI and SLAM scores were 9 (range 2–24) and 12 (range 5–26), respectively.

Significant decreases of both SLEDAI-2K and SLAM were seen at week 12 (p=0.018 and p=0.003, respectively; n=18), 26 (p=0.008 and p=0.002, respectively; n=15), 52 (p=0.003 and p=0.044, respectively; n=12) and 104 (p=0.042 and p=0.042, respectively; n=5), as compared to baseline. Prednisolone dosages were significantly decreased compared to baseline at week 12 (p=0.012, n=18), 26 (p=0.002, n=16), 52 (p=0.005, n=12) and 104 (p=0.043, n=5). Eighteen patients had low complement at baseline. We observed no significant increases in C3 or C4 levels, with the exception of a significant increase of C4 levels at week 12 (p=0.047, n=18).

The patients with history of nephritis had at baseline a mean 24-h albuminuria of 0.25 g/d (range 0.01–1.16 g/d). No renal flare was observed during the study. The grade of proteinuria remained unchanged compared to baseline at all follow-up occasions.

One patient withdrew due to an allergic reaction. The treatment with belimumab was discontinued in 4 patients after 12 months follow-up due to inadequate or uncertain effect, and in 1 patient after 6 months follow-up due to plans for pregnancy. No severe adverse events were noted during the observation period. One male patient was diagnosed with prostate cancer (age at diagnosis 55 years) 15 months after discontinuation of belimumab. 

Conclusion

Belimumab treatment decreased SLE disease activity and reduced corticosteroid usage. Despite the limited number of patients, our observations indicate that belimumab may prevent renal flares and may be used in patients with renal involvement and persistent low-grade proteinuria.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-disease-activity-and-corticosteroid-usage-and-no-renal-flares-during-belimumab-treatment-in-patients-with-systemic-lupus-erythematosus/