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

• Published in: Seminars in arthritis and rheumatism Vol. 46; no. 6; pp. 788 - 790
• Main Authors: Staveri, Chrysanthi, MD, Karokis, Dimitrios, MD, Liossis, Stamatis-Nick C., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: Adult; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Azathioprine - therapeutic use; Belimumab; Disease Progression; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine - therapeutic use; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Lupus Erythematosus, Systemic - drug therapy; Lupus nephritis; Lupus Nephritis - chemically induced; Prednisone - therapeutic use; Rheumatology; Systemic lupus erythematosus; lupus nephritis; Systemic lupus erythematosus; belimumab; Belimumab; Lupus nephritis
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2016.09.006

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 that developed lupus nephritis de novo shortly after belimumab treatment initiation; both patients improved rapidly upon belimumab discontinuation. Results The first patient (a 30 yr-old female, with a 15 yr disease duration, receiving prednisolone, hydroxychloroquine and azathioprine, with no previous history of nephritis that was repeatedly anti-dsDNA negative) 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-hr urine protein of 1600 mg) 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 yr old female with a 19 yr 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-hr urine protein above 6000 mg) for the first time during her disease course. Her renal biopsy was compatible with a Class V membranous nephritis. Belimumab was discontinued and MMF (2 g/d) was substituted for azathioprine with her urinary protein declining to 2.7 g/d just ten 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 a few only 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.