scholarly journals Rituximab and other anti-B-cell agents in immune-mediated inflammatory rheumatic diseases

2019 ◽  
Vol 27 (1) ◽  
pp. 7-17 ◽  
Author(s):  
Е.Л. Насонов ◽  
А.М. Лила
RMD Open ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. e001898
Author(s):  
Cristiana Sieiro Santos ◽  
Sara Calleja Antolin ◽  
Clara Moriano Morales ◽  
Juan Garcia Herrero ◽  
Elvira Diez Alvarez ◽  
...  

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines.AimsTo fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine’s immunogenicity.MethodsHumoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls.ResultsPatients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines.ConclusionsPatients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.


2020 ◽  
Vol 58 (3) ◽  
pp. 304-316
Author(s):  
E. L. Nasonov ◽  
A. M. Lila

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.


2020 ◽  
Vol 58 (4) ◽  
pp. 353-367
Author(s):  
E. L. Nasonov ◽  
T. V. Beketova ◽  
T. M. Reshetnyak ◽  
A. M. Lila ◽  
L. P. Ananieva ◽  
...  

Inflammation and coagulation are key basic mechanism of protection against all potentially pathogenic mechanical and biological factors targeting human organism from inner and outer environment. On the other hand, uncontrolled inflammation results in hypercoagulation, inhibition of anticoagulation and alteration of mechanisms responsible for resolution of inflammation, while production of “procoagulant” mediators (thrombin, tissue factor and others), activation of platelets and of vascular endothelial cells maintains inflammation. All factors taken together serve as the basis for a pathological process called thromboinflammation or immunothrombosis. Currently thromboinflammation is considered in the broad sense as a universal pathogenetic mechanism of numerous widespread acute and chronic conditions, including immune-mediated (autoimmune) inflammatory rheumatic diseases, oftentimes complicated by severe irreversible damage to vital organs. Thromboinflammation gained specific attention during СОVID-19 (coronavirus disease 2019) pandemic, caused by SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). COVID-19 is considered currently as systemic thromboinflammation syndrome, manifesting via generalized thrombosis of arterial and venous macro- and microvasculature, termed as COVID-19-coagulopathy. The paper discusses common pathogenetic coagulopathy mechanisms in COVID-19 and immune-mediated (autoimmune) inflammatory rheumatic diseases (IMRDs), associated with overproduction of antiphospholipid antibodies, activation of the complement system, and dis-regulated synthesis of proinflammatory cytokines, etc. Delineating the autoimmune subtype of thromboinflammation, identification of genetic (i.e., genes encoding the complement system and others) and molecular-biologic biomarkers associated with higher occurrence of COVID-19-coagulopathy are the most relevant undertakings for the current practice. Gaining insights into mechanisms of thromboinflammation and converting them into potential pharmacotherapies of IMDs would facilitate and accelerate the drafting of effective therapeutic strategies for COVID-19. 


2019 ◽  
Vol 10_2019 ◽  
pp. 51-59
Author(s):  
Vlasova G.A. Vlasova ◽  
Perminova S.G. Perminova ◽  
Kosheleva N.M. Kosheleva ◽  
Nazarenko T.A. Nazarenko ◽  
◽  
...  

2021 ◽  
Vol 72 (1) ◽  
pp. 1-5
Author(s):  
Božidar Pocevski ◽  
Slavica Pavlov-Dolijanović

Introduction: Silicone breast implants (SBI) have been used since 1962 in the reconstruction of post-mastectomy cases, in augmentation of the breast, or for cosmetic purposes, while fillers with biopolymer (FB) have been used since the 1990s. Today, they are considered adjuvants of the immune system. Most complications of SBI and FB are local in nature, but some patients experience systemic symptoms, which are defined as adjuvant-induced autoimmune inflammatory syndrome (ASIA). Aim: The aim of this study is to demonstrate the possible association of silicone breast implants and FB with the development of immune-mediated inflammatory rheumatic diseases (IMIRD). Material and methods: The research represents retrospective study which involved 15 female patients with immune-mediated inflammatory rheumatic diseases, 6 of whom were patients with implanted silicone breast implants for cosmetic reasons, and 9 patients with placement of fillers with biopolymer on the lips. Results: The average time from silicone implantation to the onset of the first symptoms was 6.10 ± 5.3 (range 6 months to 24 years). The following immune-mediated inflammatory rheumatic diseases were recorded: 3 patients with systemic sclerosis (SSc), 3 patients with undifferentiated arthritis, 3 patients with seropositive rheumatoid arthritis, 1 patient with systemic lupus erythematosus, 2 patients with undifferentiated SCTD, 2 patients with mixed connective tissue disease, and one patient with unexplained systemic disease. Seven patients had the Raynaud phenomenon. Spontaneous abortions were reported in 2 patients. Conclusion: Earlier reports that silicone breast implants and biopolymer fillers are safe, today are changing with the description of ASIA syndrome.


2021 ◽  
Vol 59 (4) ◽  
pp. 384-393
Author(s):  
E. L. Nasonov ◽  
A. S. Avdeeva

In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.


2018 ◽  
Vol 8 (1) ◽  
pp. 21 ◽  
Author(s):  
Roberta Gualtierotti ◽  
Angelo Marzano ◽  
Francesco Spadari ◽  
Massimo Cugno

Oral manifestations are frequent in patients with rheumatic diseases. The aim of this review is to offer readers practical advice concerning the onset, diagnosis and treatment of the main oral manifestations encountered in rheumatological and dental clinics. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, periodontal disease, and dysphagia may be the first expression of a number of rheumatic diseases. Some of these manifestations are aspecific and very frequent, such as oral aphthosis, which can be the first manifestation in patients with systemic lupus erythematosus; some are potentially dangerous, such as jaw claudication during the course of giant cell arteritis; and some are very rare but peculiar, such as strawberry-like gingivitis in patients with granulomatosis with polyangiitis. Other oral manifestations are due to adverse reactions to disease-modifying anti-rheumatic drugs. Oral alterations in rheumatic diseases are frequently overlooked in clinical practice, but their prompt recognition not only allows the local lesions to be appropriately treated, but also makes it possible to identify an underlying systemic disease.


2020 ◽  
Vol 65 (1-2) ◽  
pp. 61-67
Author(s):  
B. S. Belov ◽  
G. M. Tarasova ◽  
N. V. Muravyova

Comorbid infections have a significant effect on morbidity and mortality in modern rheumatology, especially in immune-mediated inflammatory rheumatic diseases (IMIRD). In this regard, vaccination is becoming increasingly important in the prevention of infections in IMIRD. The article analyzes an updated version of the recommendations for vaccination of adult patients with IMIRD, proposed by experts of the European League Against Rheumatism at the end of 2019. The safety and immunogenicity of vaccination associated with the prevention of various infections in patients with IMIRD are discussed. The main directions of future research on this issue are outlined.


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