Adjunctive subcutaneous (SC) belimumab plus standard care improves systemic lupus erythematosus (SLE) Responder Index (SRI4) response and decreases disease flares, according to results recently published in Arthritis and Rheumatology.
An intravenous (IV) formulation of belimumab, a recombinant human monoclonal antibody that inhibits B lymphocyte stimulator, was approved by the US Food and Drug Administration (FDA) for the adjunctive treatment of SLE; however, it is understood that IV administration poses financial and logistical challenges for patients.
In this study, a team of investigators led by William Stohl, MD, of the University of Southern California, Los Angeles, sought to evaluate the safety, efficacy, and tolerability of SC belimumab in patients with active SLE.
The investigators conducted a 52-week, randomized, double-blind, placebo-controlled study in 839 patients with moderate to severe SLE. Ultimately, 836 patients received treatment: weekly subcutaneous belimumab 200 mg or placebo plus standard SLE therapy for 52 weeks. The primary end point was SRI4 response at week 52.
Prior to the end of the study, 159 patients withdrew (citing adverse events, patient request, and/or disease progression/lack of efficacy). Of the remaining patients, SLE severity as measured by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 10.5 in the belimumab group and 10.3 in the placebo group.
More than 61% of patients in the belimumab group were deemed SRI4 responders compared with 48.4% of patients who received placebo. The statistically significant difference was apparent as early as week 16 and was sustained through week 52 (odds ratio [OR] 1.68; 95% CI, 1.25-2.25; P =.0006). Compared with placebo, patients treated with belimumab were nearly 50% less likely to experience a severe disease flare (hazard ratio [HR] 0.51; 95% CI, 0.35-0.74; P =.0004) and saw improvements in time to severe disease flare (median 171 days vs 118 days). In addition, 18.2% of patients in the treatment group (n=335) were able to reduce their corticosteroid use by ≥25% (≤7.5 mg/d) in weeks 40 to 52 compared with 11.9% in the placebo group (n=168) (OR 1.65; 95% CI, 0.95-2.84; P =.0732), and fewer patients in the treatment group had to increase their corticosteroid use, with significant differences observed between the groups during weeks 20 to 52 (excluding week 32) (8.1% vs 13.2%; OR 0.55; 95% CI, 0.34-0.87; P =.0117).
In subgroup analyses, scores on the FACIT-Fatigue scale significantly improved from baseline in the treatment group compared with placebo at weeks 8, 36, and 52 (P =.0130).
Overall, 80.8% of patients in the belimumab group and 84.3% in the placebo group experienced at least 1 adverse event, with the most common being infections and infestations. Serious adverse events, which were reported in 10.8% of the belimumab group and 15.7% of the placebo group, included infections and infestations, renal and urinary disorders, and disorders of the nervous system. Treatment-related adverse events included injection site reactions, all of which were mild or moderate in severity. In the treatment group, 3 deaths were reported, all due to infection. Other reported events included herpes zoster, depression, and suicidal ideation. Worsening of immunoglobulin G (IgG) hypoglobulinemia from grade 0 to 2 and grade 0 to 4 was reported in 9 patients, 5 of whom were in the treatment group.
Notably, adverse events were more common in patients with the highest body weight (≥78.25 kg) compared with patients with the lowest (˂55.05 kg).
The investigators concluded that SC belimumab 200 mg reduced SLE disease activity and had a treatment effect similar to that seen with IV belimumab. While the current study was not intended to establish equivalence between the 2 formulations, “the 2 previous belimumab IV trials and the present belimumab SC trial each met their respective primary end points and demonstrated consistent and significant clinical benefits of belimumab plus standard SLE therapy in patients with SLE.”
Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in system lupus erythematosus: a fifty-two-week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016-1027. doi:10.1002/art.40049