Systematic Review: Anifrolumab and Belimumab Improve Disease Control in Systemic Lupus Erythematosus; Voclosporin and Belimumab Effective in Lupus Nephritis
20 Oct, 2024 | 14:26h | UTCBackground: Systemic lupus erythematosus (SLE) management remains challenging due to disease heterogeneity and varying severity. New studies since the 2019 EULAR recommendations necessitate an update to inform clinical practice.
Objective: To analyze new evidence (2018–2022) for SLE management to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.
Methods: Systematic literature reviews (SLRs) were conducted in Medline and Cochrane Library databases, covering publications from January 2018 to December 2022. Research focused on five domains: (1) efficacy and safety of SLE treatments, (2) benefits of remission/low disease activity, (3) risks of treatment tapering/withdrawal, (4) management of SLE with antiphospholipid syndrome, and (5) safety of varicella zoster virus (VZV) and SARS-CoV2 immunizations.
Results: A total of 439 relevant articles were identified, predominantly observational studies of low or moderate quality. High-quality randomized controlled trials (RCTs) documented the efficacy of anifrolumab, a type 1 interferon receptor inhibitor, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN) when compared with standard care. For specific organ manifestations outside LN, high-quality data were lacking. Multiple observational studies confirmed the benefits of attaining clinical remission or low disease activity, reducing the risk of adverse outcomes. Two RCTs with some concerns found higher relapse rates in patients who discontinued glucocorticoids or immunosuppressants in SLE and LN, respectively; however, observational studies suggest that treatment withdrawal may be feasible in a subset of patients.
Conclusions: Anifrolumab and belimumab achieve better disease control than standard care in extrarenal SLE, while combination therapies with belimumab and voclosporin showed higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favorable long-term outcomes. In patients achieving these targets, glucocorticoids and immunosuppressive therapy may be gradually tapered.
Implications for Practice: Clinicians should consider anifrolumab and belimumab for extrarenal SLE, and belimumab and voclosporin for LN. Monitoring and aiming for remission or low disease activity can reduce adverse outcomes. Gradual tapering of glucocorticoids and immunosuppressants may be considered in patients achieving these targets, with careful monitoring for relapse.
Study Strengths and Limitations: Strengths include comprehensive SLRs and inclusion of recent high-quality RCTs. Limitations involve the predominance of low-quality observational studies, lack of high-quality data for specific organ manifestations, and potential bias in treatment withdrawal studies.
Future Research: Further high-quality RCTs are needed to assess treatments for specific organ manifestations outside LN. Long-term studies on tapering and withdrawal strategies of immunosuppressive therapies are necessary to guide safe practice.