Biologics in the management of systemic lupus erythematosus: pooled efficacy and safety

Multiple biological agents have emerged as potential new therapies for systemic lupus erythematosus (SLE). Below, we summarize a systematic literature review and meta-analysis of studies evaluating the efficacy and safety of biologics for treating patients with SLE, published by Chan et al. in BMC Rheumatology.¹

Methods

A systematic literature search was performed to identify phase II, III, or quasi-randomized control trials (RCTs) evaluating biologics for SLE. The biologics were assessed based on composite outcomes, renal outcomes, glucocorticoid dose reduction, and safety.

Key findings

Of 1,087 studies found, 44 (comprising 15 drug categories, 25 biological agents, and 16,889 patients with SLE) were included in the analysis. The pooled efficacy and safety results are presented in Figure 1.

AE, adverse event; BICLA, British Isles Lupus Assessment Group-Based Composite Lupus Assessment; GC, glucocorticoid; N, number of patients; NR, not reported; RCT, randomized controlled trial; SAE, serious AE; SLE, systemic lupus erythematosus; SRI, SLE Responder Index.
*Data from Chan J, et al.¹

 The improvement in outcomes was primarily observed in the following groups of biologics, compared with controls:

Anti‑interferon monoclonal antibody

• Anifrolumab significantly increased British Isles Lupus Assessment Group-Based Composite Lupus Assessment response and Systemic Lupus Erythematosus Responder Index (SRI) 5, 7, and 8 at Week 52, and reduced prednisone dose to ≤10 mg/day. Adverse events (AEs) were increased, with a higher incidence of herpes zoster infections, but fewer serious AEs.
• Rontalizumab significantly tapered prednisolone to ≤10 mg/day; other outcomes did not achieve significance.
• Sifalimumab significantly improved SRI 4 and 6 at 52 weeks, but also increased herpes zoster infections.

Anti BAFF/BLyS and APRIL monoclonal antibody

• Belimumab treatment significantly improved SRI 4 to 8 at 52 weeks, tapered prednisone dose to ≤7.5 mg/day, increased combined partial and/or complete renal response at 2 years; there was no differences in SAEs.
• Blisibimod significantly reduced prednisone dose to <10 mg/day, but also increased infusion-related AEs.
• Tabalumab significantly increased SRI 5 at 52 weeks, but had no steroid-sparing effect and was associated with increased infusion-related AEs.
• Telitacicept significantly improved SRI 4 at 52 weeks, with no differences in safety findings.

Anti‑CD20 monoclonal antibody

• Obinutuzumab significantly increased combined partial and/or complete renal response at 1 and 2 years. There were fewer infection-related ≥Grade 3 AEs, with no difference in other safety outcomes.
• Ustekinumab significantly increased SRI 4 to 6 at 24 weeks, with no safety concerns.

 

Key learnings

In patients with non-renal SLE, anifrolumab, belimumab, sifalimumab, tabalumab, and teliacicept are effective; with the first two offering the added advantages of tapering steroids.  In patients with lupus nephritis, belimumab and oblinutuzumab are effective Before initiating anifrolumab or sifalimumab, patients should consider herpes zoster vaccination