Rituximab Therapy for Primary Sjögren’s Syndrome

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.

The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology

“…CD20 expressed during the transition from pre-B cells to mature B cells and is lost during the development of plasma cells [58].Rituximab, a monoclonal antibody against CD20, is a widely used in many autoimmune conditions with different effect, making its use in pSS a controversial one. One clinical trial of 133 patients conveyed the statistically significant (p<0.05) finding of improved unstimulated salivary flow rates at week 36 and 48 in the rituximab (anti-CD20) group (n = 67) compared with placebo group (n = 66) [59].This was validated by Meijer et al, finding statistically increasets in salivary flow rates in the group given rituximab at days 1 and 15 versus the placebo after 48 weeks [60].However, its safety and long-term efficacy in pSS has yet to be shown, which may be attributed to the persistence of pathogenic autoantibodies secreted by plasma cells [61]. Anti-CD20 and anti-CatS/MHCII therapies may be viable for options in the treatment of pSS symptoms.…”

Correlations between the histopathological alterations in minor salivary glands and the clinically suspected Sjögren’s syndrome

“…The interferon-γ, IL-17, IL-21, or the overstimulated B-cell products (excessive amounts of various antibodies) play multifaceted roles [ 24 ], and these findings have initiated therapeutic attempts at B-cell depletion. Although these strategies are logical and encouraging, the results are still indecisive [ 18 , 25 , 26 ]. Moreover, some innovative and promising novel trials are also under investigation [ 27 ].…”

Building a Better Silver Bullet: Current Status and Perspectives of Non‐Viral Vectors for mRNA Vaccines

“…[ 108 ] In addition, the intrinsic shortcomings of PEI, such as poor biodegradability and toxicity of polycations, also limit its wide applications. Specifically, PEI will interact with negatively charged serum proteins [ 109 ] and rupture the blood cells during blood circulations, [ 110 ] resulting in polymer aggregations. Reducing the molecular weight of PEI has been confirmed as an efficient approach to address the above‐mentioned problems.…”