In a subset of patients with systemic lupus erythematosus (SLE) demonstrating hypocomplementemia and anti-double stranded DNA (anti-dsDNA) positivity, weekly belimumab treatment was safe and effective and superior to placebo for reducing disease activity over 52 weeks, according to findings published in Arthritis & Rheumatology.
The availability of subcutaneous belimumab has made self-administration, compared with intravenous infusions, the preferred therapeutic modality for most patients with SLE. This analysis examined participants from a larger phase 3, double-blind, placebo-controlled trial (Clinicaltrials.gov identifier: NCT01484496) who were anti-dsDNA positive (≥30 IU/mL) and hypocomplementemic (C3 <90 mg/dL and/or C4 <10 mg/dL) at baseline, to determine efficacy and tolerability in this subgroup.
There were 356 patients (96.1% women; mean age, 34.6 years) in this subset with moderate to severe SLE according to Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI; ≥8) criteria. Participants were randomly assigned to receive belimumab 200 mg weekly (n=248) or placebo (n=108), in addition to standard therapy, for 52 weeks. A total of 77 (71.3%) patients receiving placebo and 207 (83.5%) receiving belimumab completed the trial.
The primary outcome was SLE Responder Index (SRI4) ratings at 52 weeks. Secondary outcomes included severe flare incidence, corticosteroid reduction, and change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline.
At 52 weeks, individuals who received belimumab demonstrated better SRI4 responses compared with those receiving placebo (64.6% vs 47.2%; odds ratio [OR], 2.23; 95% CI, 1.36-3.64; P =.0014). Post hoc analysis that excluded SELENA-SLEDAI anti-dsDNA and complement components of SRI4 resulted in 60.6% vs 44.4% (OR, 2.13; 95% CI, 1.30-3.51; P =.0027) SRI4 response achievement for belimumab and placebo, respectively.
The belimumab group had fewer severe flares compared with those taking placebo (14.1% vs 31.5%; hazard ratio, 0.38; 95% CI, 0.24-0.61; P <.0001). More patients in the belimumab group were able to reduce steroid dosage by ≥25% compared with those in the placebo group (20.7% vs 11.4%; OR, 2.08; 95% CI, 0.91-4.77; P =.0844). Improvement of ≥4 on FACIT-Fatigue scores was also significantly improved in the belimumab group vs the placebo group (44.8% vs 33.3%; OR, 1.82; 95% CI, 1.10-3.01; P =.0199).
The safety profile of belimumab was acceptable and adverse events between the groups were similar. There were 194 (78.2%) and 88 (81.5%) treatment-emergent adverse events in the belimumab and placebo groups, respectively, of which 79 (31.9%) and 29 (26.9%), respectively, were considered treatment related. Serious adverse events occurred in 33 (13.3%) and 25 (23.1%) patients taking belimumab and placebo, respectively. Infections and infestations were most common. There were 3 deaths in the belimumab group and 2 in the placebo group.
Study limitations included a lack of statistical power for the corticosteroid end point and the exclusion of certain patients (SELENA-SLEDAI <8, active nephritis, active central nervous system disease), which may affect the applicability of belimumab in a wider population.
Belimumab benefited this subset of patients with SLE by lowering disease activity, improving fatigue, and reducing flare incidence and steroid use compared with placebo. Subcutaneous administration was well tolerated and efficacious for the treatment of SLE in individuals with hypocomplementemia and anti-dsDNA positivity and is recommended for therapeutic use.
Please see original article for a full list of disclosures.
Doria A, Stohl W, Schwarting A, et al. Efficacy and safety of subcutaneous belimumab in anti-dsDNA-positive, hypocomplementemic patients with systemic lupus erythematosus [published online April 18, 2018]. Arthritis Rheumatol. doi:10.1002/art.40511