P159 New kids on the block - real-world experience of using belimumab, obinutuzumab and voclosporin in systemic lupus erythematosus. A retrospective cohort study in University College London Hospital

Background/Aims The treatment landscape for systemic lupus erythematosus (SLE) is evolving with targeted biologics. Belimumab is approved for active, autoantibody-positive non-renal SLE; after efficacy in BLISS-52, BLISS-76, BLISS-NEA trials but not in EMBRACE. Obinutuzumab, a humanized type II anti-CD20 monoclonal antibody has shown potential in lupus nephritis (LN) in the REGENCY trial. Voclosporin, a calcineurin inhibitor was recently approved in LN. Clinical trial patients are selected carefully minimising those with more complex disease. Real-world data is vital to assess outcomes in clinical practice. This study evaluated the real-world use of belimumab, obinutuzumab and voclosporin in a single UK tertiary centre (UCLH) Methods We conducted a retrospective analysis of SLE patients treated with belimumab (n = 25), obinutuzumab (n = 8) and voclosporin (n = 3) for at least six months in our SLE clinic. Clinical response was assessed using the BILAG-2004 disease activity index at baseline, 6 months and 12 months, if continued use. Serological response was evaluated by changes in anti-dsDNA antibody titres and C3 levels. Renal response was assessed by serum creatinine and urine protein: creatinine ratio (PCR). Statistical analysis included paired t-tests and Wilcoxon test Results In the belimumab cohort, 14 patients (56%) had treatment >6 months: At 6 months compared to baseline, BILAG scores (calculated numerically) showed a significant reduction (mean difference -6.96, p = 0.0001), sustained at 12 months (p = 0.0213). Anti-dsDNA antibody titres decreased by 51% (p < 0.0001) and 64% at 12 months (p = 0.0025), with a concurrent significant rise in C3 (p = 0.0003). In the obinutuzumab cohort, the BILAG score decreased 17→7.1 (p = 0.0003), anti dsDNA −94 IU/mL (p = 0.037), and C3 (+0.23 g/L, p = 0.066). Prednisolone decreased by 7 mg/day (p = 0.085). Median urine PCR decreased from 372 mg/mmol, IQR 280-619 to 93.5 mg/mmol, IQR 69-136 (p = 0.018). Mean serum creatinine improved (113 → 105 µmol/L). In the voclosporin cohort, BILAG score improved 11→2.3 (p = 0.22) and dsDNA reduction (p = 0.02). Prednisolone dose fell from 15 → 5 mg/day. Median urine PCR dropped from 297 mg/mmol, IQR 238-300 to 44 mg/mmol, IQR 38-67; but not statistically significant (p = 0.25) due to small sample size. Two of the three voclosporin-treated patients experienced rising creatinine levels, leading to drug discontinuation (at 7 months and 1 year of therapy). Conclusion This real-world analysis, albeit in a small patient population, demonstrates the effective use of belimumab and obinutuzumab in managing SLE; with more data needed on voclosporin. Belimumab provided significant clinical and serological improvement in this heterogenous patient population, aligning with most of trial data. Obinutuzumab demonstrated meaningful gains in multiple domains, especially in renal parameters. Voclosporin showed urine PCR and serological improvement but a rising creatinine trend. Continued follow-up will determine durability of response and long-term safety of these agents.