New onset of lupus nephritis in two patients with SLE shortly after initiation of treatment with belimumab

Abstract

Purpose: Belimumab is currently approved for the treatment of patients with active SLE despite standard treatment. However, it has not been formally tested for patients with lupus nephritis because such patients had been excluded from the clinical trials. In this report, we present two patients with SLE who developed lupus nephritis de novo shortly after belimumab treatment initiation; both patients improved rapidly upon belimumab discontinuation.

Results: The first patient (a 30-year-old female, with a 15-year disease duration, receiving prednisolone, hydroxychloroquine, and azathioprine, with no previous history of nephritis that was repeatedly anti-dsDNA negative) had exacerbation of a facial butterfly-like rash developed after 3 months of belimumab treatment initiation. Concomitantly, her urinalysis became abnormal for the first time during her long follow-up (15-20 red blood cells per hpf, and a 24-h urine protein of 1600mg), and a renal biopsy documented the diagnosis of a Class III (WHO classification). Her anti-dsDNA titers became highly positive for the first time. Belimumab was discontinued and her proteinuria and abnormal urinalysis reverted to normal rapidly, and before MMF administration was approved by local regulatory authorities. Our second patient (a 38-year-old female with a 19-year disease duration) was being treated with prednisone and azathioprine. Two months following belimumab treatment initiation, she became edematous and had an active urine sediment (50-60 rbc per hpf, dysmorphic, and a 24-h urine protein levelabove 6000mg) for the first time during her disease course. Her renal biopsy was compatible with a Class V membranous nephritis. Belimumab was discontinued and MMF (2g/d) was substituted for azathioprine with her urinary protein declining to 2.7g/d just 10 days afterwards.

Conclusions: In this report, apart from our two patients, we discuss the relevant literature consisting of a handful of studies and case reports. The studies analyze patients with renal involvement treated with belimumab and are inconclusive. There are only a few case reports in which belimumab along with other agents had a potential benefit, although not straightforward. There is only one case report with striking similarities to the two patients with SLE we report herein. It could be claimed that belimumab was unable to prevent the appearance of lupus nephritis during a potentially serious disease exacerbation. Certainly, a causative association between belimumab treatment and the de novo appearance of lupus nephritis cannot be claimed because of our report. However, a potential association between belimumab treatment and the development of such a serious manifestation cannot be entirely excluded. In support of the latter hypothesis is the quick resolution/significant reduction of proteinuria shortly after belimumab discontinuation and before other treatment measures had any reasonable effect. Studies evaluating the potential usefulness of belimumab in patients with lupus nephritis are currently ongoing; until then, one should keep in mind unanswered questions as far as renal safety is concerned.

Keywords: Belimumab; Lupus nephritis; Systemic lupus erythematosus.