Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren’s syndrome: evidence- and practice-based guidance

Abstract

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren’s syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts’ input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus

“…Flare occurrence, target organ involvement, the inadequate response of some SLE patients to conventional immunosuppressive treatment and the side effects of broad immunosuppressives have led to the application of biologic agents in SLE treatment (Table 1) [9]. The increasing and deeper study of disease pathogenesis has contributed to the introduction of biologic agents to the treatment of lupus [75].…”

“…In 2014, the principle "treat to target" was introduced into the treatment strategy of SLE [8]. Flares, target organ involvement, refractory disease, adverse effects of conventional immunosuppressive agents and a better understanding of molecular pathogenesis of SLE as well as the availability of biologic agents led to the application of biologic agents and small molecules in SLE treatment [9,10]. New biologic agents are in development for the management of SLE with various molecular therapeutic targets.…”

ARID5B‐mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in β2GPI/anti‐β2GPI‐treated monocytes

“…To date, the mechanisms underlying APS have not been completely elucidated. APS is heterogeneous based on molecular aberrations and clinical features, thus, the investigation of the aetiology and the treatment methods is complicated 46 . Additionally, the APS's course is rather long and difficult to cure, resulting in accumulative alterations in molecular function and cell structure.…”

Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy

“…Depletion of CD20 positive B cells with rituximab is a common treatment in autoimmunity and presumed autoantibody mediated diseases 37–39 . To determine the extent to which rituximab treatment alters the autoreactome, we examined our cohort of 189 samples from patients with myasthenia gravis to identify pairs of pre- and post-rituximab treatment samples.…”