Case-1 is a 42-year-old East Timorese man who was diagnosed with SLE/mixed connective tissue disease overlap at age 27-years-old, with serositis and positive serology (ANA 1:1280, anti-dsDNA 550 IU/ml, extractable nuclear antigens positive for anti-RNP, anti-SSA, anti-SSB and anti-Smith). He was initially lost to follow-up but represented 6-years-later with renal impairment (sCr 111umol/L), haematoproteinuria (uPCR 0.7g/mmol, > 1000x10^6/L erythrocytes in urine microscopy) and hypoalbuminemia (13g/L). His kidney biopsy showed Class IV/V LN and he was commenced MMF 3g/day and prednisolone 60mg daily. He achieved PRR 7 months later (uPCR 0.17g/mmol, sCr 90umo/L) but subsequently had further renal and extra-renal relapses over the next 6 years, managed with high dose glucocorticoids, tacrolimus, rituximab (to which he developed an infusion reaction with rash and diarrhoea) and three courses of CYC. A repeat biopsy showed ongoing active Class IV/V LN with focal crescent formation and segmental sclerosis, therefore belimumab was introduced to the patient’s treatment in combination with steroids and MMF. He achieved PRR 18 months later with a renal biopsy showing improvement, but not complete resolution of renal activity. Since starting belimumab, there has been improvement in serum albumin (> 30g/L), lupus serology and SLEDAI-2K scores, with remission of digital chilblains, another SLE manifestation refractory to previous immunosuppressive agents. Maintenance prednisolone dose has been reduced to 4mg daily. Since commencing belimumab, he has not experienced clinically significant infections or hypogammaglobinaemia.
Case-2 is a Caucasian woman who was diagnosed with SLE with symptoms of arthralgia, lethargy, leukopenia (neutrophils 1.9 x 109/L, lymphocytes 0.9 x 109/L) and positive serology (ANA 1:1280, anti-dsDNA 149 IU/L, C3 0.7g/L and C4 0.1g/L). Treatment with prednisolone (5-8mg daily), hydroxychloroquine 200mg daily and azathioprine 75mg daily was initiated. Three years later, she had rising anti-dsDNA antibody levels (1083 IU/L) and proteinuria (uPCR 0.25g/mmol) with preserved renal function (sCr 66umol/L). A renal biopsy showed class IV LN with necrotising lesions and crescent formation. Therapy was changed to MMF 3g/day and prednisolone 20mg daily (dose unable to be escalated due to its effects on mood and sleep). She achieved CRR at 12 months (sCr 62umol/L, uPCR 0.03g/mmol), with normalisation of complement levels and improvement in dsDNA (83IU/L) and SLEDAI-2K scores (12 to 6). However, despite receiving tacrolimus, ciclosporin, rituximab and CYC over the next 4 years for disease flares, she continued to have significant proteinuria (uPCR 1.9g/mmol) and impaired renal function (sCr 200-400umol/L). A repeat renal biopsy showed diffuse sclerotic and proliferative class IV LN with moderate to severe glomerulosclerosis and interstitial fibrosis. Although belimumab was introduced, after 4 months, further deterioration in her renal function occurred and peritoneal dialysis was commenced. Belimumab was ceased and she remained on prednisolone and MMF until she received a renal transplant 14 months later. She is now treated with prednisolone, MMF and tacrolimus with stable graft function (sCr 60‐70 umol/L) without evidence of proteinuria (uPCR < 0.01g/mmol) or LN recurrence on the 12-month graft protocol biopsy. Since commencing belimumab, she did not experience any clinically significant infections or hypogammaglobinaemia.