Abstract
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune diseases of the connective tissues, characteristic of the presentation of keratoconjunctivitis sicca and xerostomia. A cardinal pathogenetic feature of SS is B-cell hyperactivity, which has invited efforts on optimal B-cell targeted therapy, whereas conventional corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are restricted to symptomatic relief. As per the first EULAR recommendation for pSS patients published in 2020, regimens with monoclonal antibodies targeting B cells may be initiated in patients with severe, refractory systemic disease, notably rituximab (RTX), a mouse-derived monoclonal antibody that targets CD20 antigen and contributes to B-cell depletion. Nonetheless, the data available from clinical trials with RTX are often controversial. Despite the lack of promising results from two large RCTs, several positive clinical efficacies were demonstrated. This current review addressed the efficacy and safety of clinical trials available and elucidated the potential of RTX on the immune system, especially B and T cells. Furthermore, plausible explanations for the discrepancy in clinical data were also presented.
Highlights
Primary Sjögren’s syndrome is quite common, with a prevalence of 0.1–0.6% in adult population, wherein the ratio of females to males is at least 9:1, with age average of 50 years on diagnosis (Mariette and Criswell, 2018)
This review addressed the current literature available on RTX treatment in Primary Sjögren’s syndrome (pSS) patients, considering the effectiveness and safety of the clinical and biological environment
The option of therapeutic agents for autoimmune diseases should be centered around the need for explicit solutions to scientific fact-based, predictive indicators of progression, prognosis, promise of long-lasting clinical remission free from further treatment as well as safety, paucity of immediate and long-term adverse events, facility in access, simplicity in management and guaranty of a good quality of life
Summary
Primary Sjögren’s syndrome (pSS) is quite common, with a prevalence of 0.1–0.6% in adult population, wherein the ratio of females to males is at least 9:1, with age average of 50 years on diagnosis (Mariette and Criswell, 2018). The B cells in the salivary glands, or rather, the target organ of pSS, may occasionally constitute ectopic germinal centers (GCs). This review addressed the current literature available on RTX treatment in pSS patients, considering the effectiveness and safety of the clinical and biological environment. In 1997, RTX became the first approved mAb by the US FDA in regimens for relapsed/refractory non-Hodgkin’s lymphoma (NHL), and has thereon significantly benefited numerous patients with various autoimmune disorders, B-cell malignancies, including pSS (Gürcan et al, 2009). Honetheless, RTX may bind to its target CD20, rendering spatial reorganization of CD20 molecules in lipid rafts Depletion mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cytotoxicity (ADCC) and phagocytosis of the reticuloendothelial system are activated, resulting in B-cell apoptosis via cross-linking CD20 molecules (Maloney et al, 2002) (Figure 1)
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