Blisibimod, a B-cell activating factor inhibitor, was well-tolerated and efficacious in patients with systemic lupus erythematosus (SLE) in terms of steroid reduction, decreased proteinuria, and improvement in serological markers, according to the results of the phase 3 Clinical and Health Assessments with Blisibimod SC, Study 1 (CHABLIS-SC1) trial (ClinicalTrials.gov identifier, NCT01395745) published in the Annals of the Rheumatic Diseases. However, the trial did not meet the primary end point of significant improvement in the SLE Responder Index-6 (SRI-6).
B-cell activating factor inhibitors offer patients an alternative to more toxic conventional lupus therapies and have achieved adequate treatment effect and tolerability in other phase 3 trials, particularly in patients with severe active disease who present with higher corticosteroid doses, lower complement levels, and anti-double-stranded DNA (anti-dsDNA) positivity. The investigators sought to corroborate prior evidence in support of blisibimod and other B-cell activating factor inhibitors.
The CHABLIS-SC1 study was a prospective, randomized, double-blind, placebo-controlled trial that included 442 patients with SLE (mean age, 36.2 years; 93.7% women). Participants demonstrated seropositivity for anti-nuclear antigen or anti-dsDNA, at least 4 American College of Rheumatology SLE criteria, and a score of ≥10 on the Safety of Estrogen in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scale.
Participants were stratified by race, proteinuria, and SELENA-SLEDAI baseline score and were randomly assigned to receive subcutaneous blisibimod 200 mg or placebo every week for 52 weeks. Participants continued corticosteroids as usual and were encouraged to taper their steroid dosage beginning at 8 weeks. The primary outcome was the percentage of individuals achieving the SLE Responder Index-6 (SRI-6) by 52 weeks.
Although blisibimod outperformed placebo (46.9% vs 42.3%) on the SRI-6, the difference between the two groups was not statistically significant (P =.352). However, a significant percentage of the blisibimod treatment group achieved corticosteroid taper between 40 and 52 weeks compared with the control group (17.2% vs 8.9%; P =.019). In addition, the overall mean steroid dosage decreased in the blisibimod group but increased in the placebo group. Upon secondary analysis accounting for steroid taper imbalances, the SRI-6 score was 23.3% in the blisibimod treatment group vs 14.3% in the placebo group (P = .056).
Patients who received blisibimod who had a baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol were significantly more likely to reach either >50% UPCR reduction or UPCR below 56.5 mg/mmol compared with patients receiving placebo. Participants taking blisibimod also demonstrated greater but nonsignificant reductions in B cells and anti-dsDNA autoantibodies, along with significantly higher complement levels compared with placebo.
The treatment and control groups had similar percentages of patients reporting treatment-emergent adverse events and serious adverse events (69.8% vs 64.8% and 13.1% vs 17.3%, respectively). The most common adverse events were urinary tract infections, upper respiratory tract infections, injection site reactions, and diarrhea. Erythema at the site was more common in the blisibimod cohort, but no serious reactions were reported.
The CHABLIS-SC1 trial showed that blisibimod therapy resulted in substantial pharmacological B-cell activating factor inhibition, with excellent effects on proteinuria and serological biomarkers. Although the primary end point was not met, the authors noted that their findings may have relevant clinical implications. They suggested that future studies try to account for potential confounding corticosteroid usage and tapering, as this appeared to substantially affect the secondary analysis.
Disclosures: This clinical trial received funding from Anthera Pharmaceuticals. JTM, MS, KCK, DW are current or prior consultants for the sponsor, Anthera Pharmaceuticals. MS was a clinical investigator in this trial. RSM and WRS are employees and shareholders of Anthera Pharmaceuticals.
Merrill JT, Shanahan WR, Scheinberg M, et al. Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial [published online March 21, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-213032