Belimumab addition to standard therapy improves results in lupus Nephritis: NEJM

Despite aggressive treatment, approximately 60% of patients with lupus nephritis do not have complete remission, and these patients have poor long-term outcomes. This risk has remained unchanged during the past three decades.

Belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, is approved for patients with active autoantibody-positive SLE who are 5 years of age or older. To date, data on the efficacy and safety of belimumab in patients with active lupus nephritis are lacking due to limitations in sample size and sample selection.

In a recent trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy (mycophenolate mofetil or cyclophosphamide–azathioprine) had a primary efficacy renal response than those who received standard therapy alone.

The findings have been published in The New England Journal Of Medicine.

This phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial under Richard Furie and team, was performed following the principles of the Declaration of Helsinki. The trial was conducted at 107 sites in 21 countries. The sponsor (GlaxoSmithKline) supported the authors in the development of the manuscript.

The inclusion criteria were patients of 18 years of age and had autoantibody-positive SLE (antinuclear antibody titers ≥1:80, anti-double-stranded DNA antibodies, or both) that fulfilled the 1982 American College of Rheumatology classification criteria for SLE. At the screening, the patients had a ratio of urinary protein to creatinine of 1 or more and biopsy-proven lupus nephritis of International Society of Nephrology and Renal Pathology Society class III (focal lupus nephritis) or IV (diffuse lupus nephritis) with or without coexisting class V (membranous lupus nephritis), or pure class V lupus nephritis within 6 months before, or during, screening.

Random allocation of patients in 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy was done. The primary endpoint at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy). Further, the time to a renal-related event or death was assessed.

The following key facts emerged on analysis.

• A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group).
• At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P=0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P=0.02).
• The risk of a renal-related event or death was lower among patients who received belimumab than among those who received a placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P=0.001).
• The safety profile of belimumab was consistent with that in previous trials.

"The current international trial showed that belimumab plus standard therapies for lupus nephritis enhanced renal responses; furthermore, the risk of a renal-related event during the trial was almost 50% lower among patients who received belimumab than among those who received standard therapy alone." concluded the authors.

For full article follow the link: DOI: 10.1056/NEJMoa2001180

Source: The New England Journal O F Medicine