SIR, Belimumab has been approved for autoantibodypositive SLE with persistent disease activity despite standard treatment [1]. With respect to LN, European League Against Rheumatism (EULAR) guidelines state that the position of belimumab needs further definition [2]. Previously another biologic, rituximab, failed to be superior over placebo when added to MMF and corticosteroids in LN [3]. However, retrospective cohort data suggest a role for rituximab in refractory LN [4]. Here we report our experience with rituximab followed by belimumab as maintenance treatment in two refractory LN patients.

Patient 1, a 32-year-old female, was diagnosed with SLE 3 years earlier based on a butterfly exanthema, discoid lupus, photosensibility, lymphadenopathy, GN and positive ANA (3+) and anti-dsDNA (3+). A kidney biopsy revealed diffuse and global proliferative GN class IV-S (A). Since her diagnosis she had received two induction regimens (MMF and Eurolupus CYC), despite which her disease flared. The latter manifested with discoid lupus, arthralgias, diffuse alopecia and persisting GN with urinary red blood cell (RBC) casts and proteinuria (SLEDAI score 22). She was re-treated with MMF induction and corticosteroids during which progressive proteinuria (8 g/day) developed (Fig. 1). Concomitant angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) induced symptomatic hypotension. At this time, pulse steroids and rituximab followed by MMF and prednisolone maintenance was initiated. This led to a partial response with a reduction of proteinuria to 3.5 g/day. Disease amelioration was hampered because MMF caused intractable nausea and weight loss that challenged her treatment adherence. Seven months after rituximab she was started on belimumab. The initiation coincided with the time B cells started to fully repopulate. In the following months her skin lesions, alopecia and arthralgia resolved. Moreover, she independently tapered her prednisolone to zero because of tremors that interfered with her daily work requiring highly developed fine motor skills. Currently, after 18 months, she remains in remission on belimumab monotherapy with proteinuria of 0.9 g/day, a reduction in ANA (1+) and anti-dsDNA (1+), C3 normalization (from a nadir of 0.7 to 1.0; normal range> 0.9 g/l) and increasing C4 levels (from a nadir of 103 to 194; normal range> 95mg/l) and a reduced number of circulating B cells (SLEDAI score 6). Patient 2, a 42-year-old male, was diagnosed with SLE 7 years earlier, presenting with nephrotic syndrome, urinary RBC casts, class IV-G (A) LN, positive autoantibodies (ENA 2+), complement usage, alopecia, anorexia and auditory hallucinations with psychosis, including cerebral white matter lesions confirming neuropsychiatric involvement. He was referred to our hospital 2 years ago with a therapy-refractory nephrotic syndrome (proteinuria 9.8 g/day, creatinine 150 μmol/l) while taking a combination of ACE inhibitors and ARBs. He was already treated with two previous induction treatments (CYC and MMF), each followed by MMF maintenance with concomitant prednisolone and HCQ. Another kidney biopsy confirmed the LN class IV-G (A) diagnosis with full-house immunofluorescence and additional focal global sclerosis and