Background/Purpose

 To investigate the efficacy and safety of belimumab in patients affected with active systemic lupus erythematosus (SLE) refractory to standard therapy in the clinical practice setting.

Methods

 Forty-one patients affected with active SLE (1997 ACR criteria), with low complement and high anti-double stranded DNA (dsDNA) antibody levels, unresponsive to corticosteroids, antimalarials and/or immunosuppressant were treated with belimumab (10 mg/kg at day 0, 14 and 28 and then every 28 days) for a median follow-up of 8.9 months (range 13.1-2.0). A total of 426 infusions of belimumab were performed. The median age of patients was 38.9 years (range 21-62) and mean disease duration 12.2 years (range 1-32). SLE Disease Activity Index 2000 (SLEDAI-2K), anti-dsDNA (tested by ELISA or Farr method), C3 and C4 serum levels, and corticosteroid daily dose were recorded at baseline and every 3 months thereafter. Disease flare was defined according to SLE flare index. Disease flare rate was evaluated in 23 patients prior and during treatment. Adverse events were carefully recorded at each clinical evaluation and were defined severe when hospitalization was required and/or death and/or life-threatening manifestations occurred.

Results

Refractory manifestations requiring belimumab were renal (41.4%), musculoskeletal (36.5%), mucocutaneous (36.5%), hematologic (21.9%), and serositic (4,8%). In the efficacy analysis we considered 34 patients followed for at least 6 months. Decrease in median SLEDAI-2K, anti-dsDNA, and corticosteroid daily dose and increase in C3 and C4 serum levels at baseline, 3, and 6 months of follow-up are reported in Table 1. Notably, a reduction in the frequency of flares was observed: 70 flare/100 patients in the 6 months before the start of belimumab and 18 flares/100 patients during the 6-month belimumab treatment (p=0.02).

Adverse events were analyzed in 23 patients. A total of 70 adverse events were obseved. Most frequent non infectious adverse events were fatigue (15%), hypertension (7%), and mild hair loss (5%). Infectious adverse events were 38 (54.2%), 34 were mild and 4 were moderate. Mild infusion reactions was observed in 2 patients (8.7%). No severe adverse events were observed.

Conclusion

 These preliminary data confirm the efficacy and tolerability of belimumab in the treatment of patients with active SLE refractory to standard treatment in the clinical practice setting. Belimumab seem to reduce the number of disease flares and this suggest that it might be useful especially in those patients with relapsing remitting pattern of disease.

Table 1. SLEDAI-2K, anti-dsDNA antibody, C3, C4 and corticosteroid daily dose at baseline, 3, and 6 months of follow-up