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Objectives SLE treatment has evolved with targeted therapies. Belimumab is approved for active, autoantibody-positive non-renal SLE in the UK. Obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, has shown potential in lupus nephritis (LN) in the REGENCY trial. Voclosporin, a calcineurin inhibitor, was recently approved for LN. As clinical trials often exclude complex cases, real-world data is vital. This study evaluated outcomes with belimumab, obinutuzumab, and voclosporin in a single UK tertiary centre (UCLH).Methods A retrospective analysis included SLE patients treated with belimumab (n=25), obinutuzumab (n=8), and voclosporin (n=3) for >=6 months. Clinical response was assessed using the BILAG-2004 index at baseline, 6, and 12 months. Serological response was evaluated by anti-dsDNA and C3 changes. Renal response was analysed in 11 LN patients (obinutuzumab and voclosporin cohorts) using serum creatinine and urine protein: creatinine ratio (UPCR). Complete renal remission (CRR) was defined as UPCR <50 mg/mmol with stable creatinine (<=15% change); partial renal remission (PRR) as >=50% UPCR reduction and <300 mg/mmol with stable creatinine. Paired t-tests and Wilcoxon tests were applied.Results In the belimumab cohort, 14 patients (56%) received >6 months of therapy. Mean BILAG score decreased significantly (-6.96; p=0.0001), sustained at 12 months (p=0.0213). Anti-dsDNA fell 51% (p<0.0001) and 64% at 12 months (p=0.0025) with C3 rising (p=0.0003).In the obinutuzumab cohort, mean BILAG score reduced 17->7.1 (p=0.0003); dsDNA -94IU/mL (p=0.037); C3 +0.23g/L (p=0.066). Prednisolone fell to 7mg/day (p=0.085). Median UPCR improved from 372 (IQR 280-619) to 93.5mg/mmol (IQR 69-136; p=0.018); mean creatinine 113->105µmol/L. One (12.5%) achieved CRR and four (50%) PRR.In the voclosporin cohort, mean BILAG score improved 11->2.3 (p=0.22); dsDNA reduced (p=0.02); prednisolone fell 15->5mg/day. Median UPCR 297 (IQR 238-300)-> 44mg/mmol (IQR 38-67; p=0.25). One (33%) achieved CRR; none PRR. Two of three patients discontinued due to rising creatinine (at 7 and 12 months).Conclusions This real-world analysis, though small, demonstrates encouraging outcomes with belimumab and obinutuzumab in SLE. Belimumab group achieved significant clinical and serological improvement. Obinutuzumab showed meaningful gains, particularly renal. Voclosporin improved proteinuria and serology but limited by rising creatinine. Continued follow-up will determine durability of response and long-term safety of these agents.