Background Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4.
Objectives To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity.
Methods 442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6).
Results The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved >50% reduction in UPCR and/or UPCR <56.5 mg/mmol. Reductions in SLE autoantibodies and B cells, and increases in complement C3 and C4 were observed with blisibimod.
Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection, urinary tract infection, injection site erythema/reaction and diarrhoea.
Conclusions Although the SRI-6 end point was not met, blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses.
Trial registration number NCT01395745.
- B cells
- systemic lupus erythematosus
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Handling editor Josef S Smolen
Contributors All authors provided substantial input to the design, conduct and/or analysis of this trial. In addition, all authors participated in the drafting of this manuscript and the responses to reviewers and approve this version for publication.
Funding This sponsorship of this clinical trial by Anthera Pharmaceuticals included all funding and oversight of all clinical operations, laboratory analyses, data collection, statistical analyses, drug manufacturing and distribution to conduct and complete the trials as described.
Competing interests 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.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Multiple EC/IRB bodies reviewed and approved this trial (in Belarus, Brazil, Colombia, Georgia, Guatemala, Hong Kong, Korea, Singapore, Malaysia, Mexico, Russia, Sri Lanka, Taiwan, Thailand and the Philippines).
Provenance and peer review Not commissioned; externally peer reviewed.
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