Use of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases: safety issues

There has been clear progress in rheumatology in recent decades with the introduction of genetically engineered biological drugs (GEBDs) as well as targeted baseline anti-inflammatory drugs, which include Janus kinase inhibitors (i-JAKs). To date, i-JAKs have been actively used and studied in various immunoinflammatory rheumatic diseases (IIRDs) – rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), as well as psoriasis, atopic dermatitis and inflammatory bowel disease. In order to summarize the accumulated experience, the experts of the European League Against Rheumatism developed a consensus, which outlined the main principles and provisions concerning the rational use of i-JAKS in patients with IIRDs. At the same time, much attention is paid to the problem of the safety of these drugs. In the present article, issues related to various aspects of the safety of the use of i-JAKs in patients with IIRDs are discussed in detail, namely: dose adjustments due to drug interactions, contraindications, pre-screening, and risk assessment. Possible adverse events related to infectious complications, malignancies, thromboembolic phenomena, and gastrointestinal perforation were analyzed. The significance of clinical and laboratory monitoring in catamnestic follow-up of patients receiving i-JAKs is emphasized. A program for further research on the mentioned problem is presented. It includes studies of the efficacy and safety of «switching» between i-JAKs in patients with poor tolerance of a particular drug or who do not respond to treatment, evaluation of the effect of i-JAKs on comorbidities including cardiovascular disease and osteoporosis, studies of the long-term safety of i-JAKs based on actual practice data, and of the effectiveness and safety of i-JAKs and GEBDs combination therapy in patients with severe RA or other conditions, etc. This consensus is designed to inform and target physicians seeking to achieve optimal use of these drugs in patients with IIRDs, as well as patients themselves and other interested parties, including facility administrators. The recommendations will undoubtedly be expanded and supplemented as new data accumulate.

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Anti-inflammatory drugs and immunogenicity of vaccines in patients with rheumatic diseases

Medical Council ◽

10.21518/2079-701x-2021-19-177-187 ◽

2021 ◽

pp. 177-187

Author(s):

B. S. Belov ◽

N. V. Muravyeva ◽

M. M. Baranova

Keyword(s):

Clinical Practice ◽

Rheumatic Diseases ◽

Kinase Inhibitors ◽

Genetically Engineered ◽

Janus Kinase ◽

Inflammatory Rheumatic Diseases ◽

Virus Infections ◽

Vaccine Response ◽

Biological Drugs ◽

Negative Effect

The problem of comorbid infections in rheumatology seems to be very relevant in connection with the active introduction into clinical practice of innovative disease-modifying anti-rheumatic drugs (DMARDs), the so-called targeted DMARDs (tDMARDs), as well as genetically engineered biological drugs (biologics), the action of which is directed at specific links in the pathogenesis of immuno-inflammatory rheumatic diseases. With the accumulation of global clinical experience, the association of the use of these drugs with an increasing risk of developing comorbid infections of various nature and localization has become clearly traced. The real way out of this situation seems to be the creation, improvement and introduction into clinical practice of various vaccines. At the same time, a number of anti-rheumatic drugs may have a certain negative effect on the immunogenicity of some vaccines, which may lead to a decrease in the preventive effectiveness of the latter. This review presents the latest data on the effect of various anti-rheumatic drugs on the immunogenicity of vaccines against influenza, pneumococcal and herpes virus infections, viral hepatitis B, yellow fever and COVID-19 used in rheumatological patients. It has been shown that the anti-B-cell drug ritux imab has a significant negative effect on the immunogenicity of vaccines, which increases with a shortening of the time between immunization and the use of the drug. Methotrexate also negatively affects the immunogenicity of most vaccines, but to a lesser extent. Abatacept probably reduces the immunogenicity of vaccines, although studies were performed in the absence of adequate control groups. Tumor necrosis factor inhibitors-α and tDMARDs (janus kinase inhibitors) reduce the absolute values of antibody concentrations for many vaccines, but apparently do not have a significant effect on the frequency of patients who have achieved seroprotection. Inhibitors of interleukin (IL) -6, IL-12 / IL-23 and IL-17 practically do not affect the immunogenicity of vaccines. The accumulated data on the effect of the above drugs on the immunogenicity of the vaccine against SARS-CoV-2, apparently, are similar to those obtained in studies on vaccination against other infections in patients with immuno-inflammatory rheu matic diseases. Further clinical studies are needed to assess the effect of immunosuppressive therapy on the vaccine response and to develop methods for its optimization.

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New directions of pharmacotherapy of immune - inflammatory rheumatic diseases

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.08.000406 ◽

2019 ◽

Vol 91 (8) ◽

pp. 98-107 ◽

Cited By ~ 1

Author(s):

E L Nasonov

Keyword(s):

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Kinase Inhibitors ◽

Systemic Vasculitis ◽

Janus Kinase ◽

Inflammatory Rheumatic Diseases ◽

Dramatic Improvement ◽

Janus Kinase Inhibitors ◽

Autoimmune Pathology ◽

Factor Α

Deciphering immunopathogenesis, expanding the scope of diagnostics and developing new methods for treating human autoimmune diseases are among the priority areas of XXI century medicine. Particularly widely autoimmune pathology is presented in immunoinflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, systemic vasculitis associated with the synthesis of antineutrophilic cytoplasmic antibodies, Sjogren's syndrome, idiopathic inflammatory myopathies and other other types of others. Deciphering the pathogenesis mechanisms of IIRD created the prerequisites for improving pharmacotherapy, which in the future should lead to a dramatic improvement in the prognosis for these diseases. The review discusses new approaches to IIRD pharmacotherapy associated with the inhibition of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, IL-17, IL-23, and the prospects for using Janus kinase inhibitors, depending on the prevailing pathogenesis mechanisms - autoimmunity or autoinflammation.

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