Real-world study finds rates of serious infection are similar whether taking rituximab, belimumab or standard-of-care therapy for SLE.
A large prospective real-world study in British SLE patients has found that rates of serious infection are similar whether taking rituximab, belimumab or standard-of-care therapy.
Multimorbidity (diabetes and hypertension), hypogammaglobulinaemia and oral glucocorticoids ≥10mg per day increased the risk of serious infections, while concomitant use of immunosuppressants was associated with a decreased risk.
“This study provides reassurance that there is not a significantly increased infection risk with rituximab or belimumab treatment compared with the standard of care in patients with moderate-to-severe SLE,” wrote the authors, led by doctors Mia Rodziewicz and Sarah Dyball of the University of Manchester.
“Assessments of the individual infection risk in patients with SLE should consider and address the glucocorticoid burden, multimorbidity and hypogammaglobulinaemia.”
Patients with moderate-to-severe SLE were recruited to the British Isles Lupus Assessment Group Biologics Register (BILAG-BR) if they had started a new biologic within the last 12 months or standard of care drug (mycophenolate mofetil, cyclophosphamide, azathioprine or a calcineurin inhibitor) within the last month. People taking biologics other than rituximab or belimumab were excluded from the analysis due to small numbers.
There were 1048 patients from 64 centres included in the study, with most (71%) taking rituximab, 11% taking belimumab and 17% standard of care.
The primary outcome was rate of serious infections – defined as those requiring intravenous antibiotics, hospital admission, or resulting in morbidity or death – within the first 12 months of therapy.
Of the total cohort, 7% had serious infections, with 118 serious infections occurring in 76 patients. Compared with standard of care, the hazard ratio for patients on rituximab was 1.68 (95% CI 0.60-4.68) and for belimumab was 1.01 (0.21-4.80). The main infections were respiratory, skin and soft tissue, and gastrointestinal.
Risk of serious infection increased as oral glucocorticoid dose increased, with 10mg or more per day doubling the risk (HR 2.38 [1.47-3.84]). Hypogammaglobulinaemia and multimorbidity were also associated with increased risk while additional concomitant immunosuppressive drugs appeared to reduce the risk (HR 0.60 [0.41-0.90] per additional drug).
“We propose that, when considering serious infection risk, immunosuppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use in patients with moderate-to-severe SLE,” concluded the authors.
Strengths of the study included the ability to collect accurate information from study centres relating to serious infections and mortality, and the inclusion of patients often excluded from clinical trials due to comorbidities or underrepresented in clinical trials (Black and Asian patients).
There were several limitations of the study, including the relatively small number of belimumab and standard of care patients, resulting in wide confidence intervals. Being a non-randomised observational cohort study, inherent differences between groups may have led to confounding. The authors pointed out that serious infections may have been missed if they were recorded outside of the patient’s study centre.
The study didn’t have much data on covid infections – with risk of severe outcomes known to be increased in rituximab patients – partly due to the cut-off of February 2021 and also the impact of the pandemic on recruitment and data collection.
In an accompanying comment, doctors Yann Nguyen and Nathalie Costedoat-Chalumeau pointed to the heterogeneity of the standard of care group, the short time frame of 12 months after initiation and the small number of infections as limitations.
However, they said, findings of the study may help physicians reduce the risk of infections.
Measures could include avoiding high doses of glucocorticoids (in keeping with international guidelines) with the help of conventional synthetic or biologic DMARDs; improving vaccination rates in SLE patients; avoiding rituximab in patients with low IgG concentrations where possible; and “systematically treating patients with SLE with hydroxychloroquine, unless contraindicated”, shown to reduce risk of serious infections.
Excellent work @sarahdyball1 @MiaRodziewicz! This is really impressive stuff and so important! Your findings look very reassuring to me. I think this definitely helps give clinicians more confidence when risk stratifying therapy! 👏🏻 Hope to discuss with you at #EULAR2023
— Chris Wincup (@chriswincup) April 25, 2023
