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Background and Aims

We aimed to assess the early risk of infection following rituximab in a large national biologics register.

Methods

Patients initiating rituximab or standard-of-care (SoC) in the UK-national SLE biologics registry (2010-21) were included. Infection and mortality data were collected from study centres and the Office for National Statistics in the first 12-months. Serious infections included those requiring intravenous antibiotics, hospital admission, or resulting in death. A logistic regression model adjusted for age and sex tested the association of baseline variables with serious infection within the first year.

Results

We included 931 patients; 764 rituximab and 167 SoC (mycophenolate=126, azathioprine=46 and/or cyclophosphamide=38).

At baseline, rituximab patients had a longer disease duration (4 vs 2 years, p=0.04), increased previous immunosuppressant-use (2 vs 1, p<0.0001), more obstructive airways disease (14% vs 7%,p=0.02) and lower maintenance steroid (10mg vs 12.5mg, p<0.0001) and baseline serum IgG (12 vs 15g/L, p=0.024).

In the first year following treatment initiation, there was no difference in the number of serious infections between rituximab and SoC (8% vs 6%,p=0.471), or number of recurrent serious infections (2.5% Vs 1.2%,p=0.309). One rituximab-treated individual died of infection. Commonest infection sites were respiratory (23%), bone/skin (13%) and ENT (10%).

In rituximab-treated patients, cumulative comorbidities (OR 1.34, 95%CI 1.08-1.65), maintenance steroid dose (OR 1.05, 95%CI 1.01-1.08) and hypogammaglobulinaemia (OR 2.3, 95%CI 1.06-5.18) were associated with increased risk of serious infection.

Conclusions

Rituximab-treated SLE patients do not demonstrate an increased risk of serious infections. Baseline hypogammaglobulinaemia, multimorbidity and higher usual oral steroid correlate with infection risk in rituximab-treated patients.

Background and Aims

Autoantibodies are produced by over-active immune cells in systemic lupus erythematosus (SLE).¹ Dapirolizumab pegol (DZP) is a polyethylene glycol (PEG)-conjugated antigen-binding (Fab’) fragment that inhibits CD40L.² Immunoglobulin (Ig) protein and gene expression changes in DZP-treated SLE patients from the SL0023 phase 2b study (NCT02804763) were analysed.

Methods

The study design has been reported previously.² Serum Ig levels and anti-double stranded DNA (a-dsDNA) titres were quantified from patients receiving standard of care (SOC) with 24mg/kg or 45mg/kg DZP every four weeks (Q4W). Additionally, gene expression in peripheral blood was analysed by Affymetrix GeneChip microarrays and quantitative (q)PCR. We present the change from baseline in serum Ig levels and Ig-related gene expression at Week (Wk)12 of SOC+DZP treatment in SLE patients. Data are reported for patients with gene expression observations at baseline or Wk12.

Results

Baseline demographics were similar between treatment groups. Reductions from baseline in median serum IgG, IgA and a-dsDNA Ig levels were observed at Wk12 in patients treated with SOC+DZP 24mg/kg Q4W (n=37) or SOC+DZP 45mg/kg Q4W (n=38) (Table). Affymetrix microarray data showed a reduction from baseline at Wk12 in Ig gene expression, including Ig heavy and lambda light chains. Longitudinal qPCR gene expression data supported these reductions.

Conclusions

SOC+DZP (24 or 45mg/kg Q4W) reduced serum Ig levels and downregulated Ig gene expression in SLE patients. This supports previous findings.³

Acknowledgements: Funded by UCB Pharma and Biogen.

References: 1.Kyttaris V. Methods Mol Biol. 2010;662:265–83; 2.Furie R. ACR. 2019; 0944; 3.Chamberlain C. ARD. 2017;76(11):1837–44.

Background and Aims

The EULAR recommendations underline the use of MMF for Lupus Nephritis (LN) but also for the treatment of moderate/severe non-renal manifestations (NLN). This study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a SLE cohort in a real-life scenario. Secondly, we investigated the MMF influence to control chronic damage progression.

Methods

We performed a longitudinal study including all the SLE patients starting MMF in our LupusClinic (from 2008 to 2020). The DRR was estimated using the Kaplan-Meier method.

Results

We evaluated 162 SLE patients (M/F 22/140). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%) followed by NPSLE (10, 6.2%) and others manifestations (12, 7.4%). We registered a median treatment duration of 30 months (IQR 55). At 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (60.5%); Figure 1. The DRR was higher in the subgroup of patients with joint involvement (75.4%, p=ns). During the overall observation period, 92 patients (59.2%) discontinued MMF. The main cause of withdrawal was the achievement of remission, observed in 20 patients (21.7%). Moreover, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last: 0.93, IQR 1, p=ns).

Conclusions

Our finding suggested that MMF is a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it was able to reduce the chronic damage progression.