New directions of pharmacotherapy of immune - inflammatory rheumatic diseases

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

Medical Council ◽

10.21518/2079-701x-2021-2-76-84 ◽

2021 ◽

pp. 76-84

Author(s):

B. S. Belov ◽

N. V. Muravyeva ◽

G. M. Tarasova ◽

M. M. Baranova

Keyword(s):

Rheumatic Diseases ◽

Kinase Inhibitors ◽

Infectious Complications ◽

Genetically Engineered ◽

Janus Kinase ◽

Biological Drugs ◽

Janus Kinase Inhibitors ◽

Safety Issues ◽

European League Against Rheumatism ◽

Poor Tolerance

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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Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects

Rheumatology Science and Practice ◽

10.14412/1995-4484-2019-8-16 ◽

2019 ◽

Vol 57 (1) ◽

pp. 8-16 ◽

Cited By ~ 20

Author(s):

E. L. Nasonov ◽

A. M. Lila

Keyword(s):

Rheumatic Diseases ◽

Kinase Inhibitors ◽

Population Level ◽

Janus Kinase ◽

Signal Molecules ◽

Inflammatory Rheumatic Diseases ◽

Great Success ◽

Medical Problems ◽

Synthetic Drugs ◽

Reduction Of Mortality

Despite the great success in the diagnosis and treatment of immuno-inflammatory rheumatic diseases (IIRD), which led to a significant improvement in the prognosis in many patients, the fundamental medical problems of this pathology – the restoration of quality of life and reduction of mortality to the population level – are far from solution. This served as a powerful impetus to the study of new approaches to pharmacotherapy of IIRD, one of which is associated with the use of low-molecular synthetic drugs that inhibit intracellular "signal" molecules-Janus kinase (JAK), the socalled Jakinibs. The current achievements and trends concerning the use of JAK inhibitors in the treatment of IIRD are considered.

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Pulmonary arterial hypertension in interferonophaties: a case report and a review of the literature

Pulmonary Circulation ◽

10.1177/2045894019869837 ◽

2019 ◽

Vol 9 (3) ◽

pp. 204589401986983 ◽

Cited By ~ 3

Author(s):

A. Trombetta ◽

S. Ghirardo ◽

S. Pastore ◽

A. Tesser ◽

E. Piscianz ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Lupus Erythematosus ◽

Kinase Inhibitors ◽

Janus Kinase ◽

Type I ◽

Systemic Lupus ◽

Janus Kinase Inhibitors ◽

Pulmonary Arterial

Background Pulmonary arterial hypertension consists in an increase of mean pulmonary arterial pressure (PAPm ≥ 25 mmHg), and may lead to right ventricular failure. Pulmonary arterial hypertension can arise in several disorders, encompassing inflammatory conditions and connective tissue diseases. The occurrence of pulmonary arterial hypertension has recently been reported in monogenic interferonopathies and in systemic lupus erythematosus, highlighting the pathogenic role of type I interferons and paving the way to therapies aimed at inhibiting interferon signaling. Case We describe a 17-year-old boy with DNase II deficiency, presenting a clinical picture with significant overlap with systemic lupus erythematosus. During treatment with the Janus kinase inhibitor ruxolitinib, he developed pulmonary arterial hypertension, raising the question whether it could represent a sign of insufficient disease control or a drug-related adverse event. The disease even worsened after drug withdrawal, but rapidly improved after starting the drug again at higher dosage. Summary and conclusion Pulmonary arterial hypertension can complicate type I interferonopathies. We propose that ruxolitinib was beneficial in this case, but the wider role of Janus kinase inhibitors for the treatment of pulmonary arterial hypertension is not clear. For this reason, a strict cardiologic evaluation must be part of the standard care of subjects with interferonopathies, especially when Janus kinase inhibitors are prescribed.

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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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Biologic therapies for the treatment of psoriatic arthritis

Journal of Korean Medical Association ◽

10.5124/jkma.2021.64.2.124 ◽

2021 ◽

Vol 64 (2) ◽

pp. 124-129

Author(s):

Tae-Jong Kim

Keyword(s):

Psoriatic Arthritis ◽

Kinase Inhibitors ◽

Phosphodiesterase Inhibitors ◽

Janus Kinase ◽

Interleukin 12 ◽

Interleukin 17 ◽

Dramatic Improvement ◽

Functional Impairments ◽

Biological Products ◽

Factor Α

Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease commonly associated with plaque psoriasis that, manifests with peripheral arthritis, dactylitis, enthesitis, and axial involvement. PsA can be progressive and harmful, resulting in joint deformities, functional impairments, low quality of life, and increased mortality. It was found that both non-pharmacologic and pharmacologic treatment could improve conditions of PsA. Recently launched biological products have become the main therapeutic agents used for treating PsA unresponsive to conventional disease modifying anti-rheumatic drugs. This paper aims at introducing available biologics for PsA management in Korea. The tumor necrosis factor-α inhibitor was the first approved biological product to show outstanding efficacy for treating PsA. Ustekinumab, designed for blocking interleukin-12/23, has been approved and widely used. Interleukin-17 inhibitors such as secukinumab and ixekizumab have also been introduced to improve the symptoms of PsA. It was found that many patients with PsA experienced a dramatic improvement in their condition after using these biological products. Additionally, new immunological modulators such as phosphodiesterase inhibitors and Janus kinase inhibitors were approved for the treatment of PsA.

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‘Should we stop or continue conventional synthetic (including glucocorticoids) and targeted DMARDs before surgery in patients with inflammatory rheumatic diseases?’

RMD Open ◽

10.1136/rmdopen-2020-001214 ◽

2020 ◽

Vol 6 (2) ◽

pp. e001214 ◽

Cited By ~ 1

Author(s):

Susan M Goodman ◽

Michael D George

Keyword(s):

Perioperative Management ◽

Kinase Inhibitors ◽

Controlled Trial ◽

Perioperative Period ◽

Janus Kinase ◽

Inflammatory Rheumatic Diseases ◽

Janus Kinase Inhibitors ◽

Symptomatic Knee ◽

Total Knee ◽

Randomised Controlled

Total hip and total knee arthroplasty) remain important interventions to treat symptomatic knee and hip damage in patients with rheumatoid arthritis, with little change in utilisation rates despite the increasingly widespread use of potent conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and targeted DMARDs including Janus kinase inhibitors and biologics. The majority of patients are receiving these immunosuppressing medications and glucocorticoids at the time they present for arthroplasty. There is minimal randomised controlled trial data addressing the use of DMARDs in the perioperative period, yet patients and their physicians face these decisions daily. This paper reviews what is known regarding perioperative management of targeted and csDMARDs and glucocorticoids.

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