Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).
The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).
In recent decades, industrialized countries have recorded a steady increase in the incidence of atopic dermatitis (AD). The pathogenesis of AD is complex and diverse and includes hereditary determinism leading to a disruption of the skin barrier, as well as the Th2 immune response, which is supported by a wide range of pro-inflammatory mediators released by immunocompetent and epithelial cells, which play a key role in the activation and maintenance of inflammation in the skin. Progress in the treatment of immunoinflammatory diseases, including in the skin, has been achieved with the advent of a new class of targeted synthetic oral immunomodulatory drugs, Janus kinase inhibitors. Janus kinases are part of the JAK – STAT intracellular signaling system; STAT proteins are responsible for signaling more than 60 cytokines, hormones and growth factors that regulate key cellular processes. Currently, second generation JAK inhibitors have been developed, such as upadacitinib (trade name Rinvoq), which distinguish them from non-selective JAK inhibitors by their selectivity for certain JAK isoforms. In June 2021, the Ministry of Health of the Russian Federation approved the use of upadacitinib (UPA) for the indication “treatment of moderate to severe atopic dermatitis in adults and children aged 12 years and older who are indicated for treatment with systemic drugs”; the drug can be used in monotherapy or in combination with topical therapy in adults at a dose of 15 or 30 mg per day depending on the individual characteristics of the course, in adolescents weighing at least 40 kg – at a dose of 15 mg per day. Results from a Phase 3 clinical trial program involving more than 2500 patients worldwide in three global key studies: Measure Up 1, Measure Up 2 (UPA monotherapy at a dose of 15 mg or 30 mg per day) and AD Up (UPA in the same doses in combination with topical glucocorticosteroids (TGCS) demonstrated high efficacy and favorable benefit/risk profile of UPA both in monotherapy and in combination with TGCS in patients with moderate to severe AD.
Two clinical cases of tofacitinib use in the management of rheumatoid arthritis (RA) patients by a rheumatologist at the outpatient stage within the framework of the “Treatment to Target” strategy are presented. The first clinical case describes the case history of a female patient (age 48 years, RA duration 20 years), which demonstrates the difficulties in selecting pathogenetic therapy for late-stage RA. Consecutively prescribed four synthetic baseline anti-inflammatory drugs (methotrexate, sulfasalazine, cyclophosphamide, leflunomide) and two genetically engineered biological drugs (infliximab, rituximab) failed to achieve remission of the disease in the patient. Decrease in disease activity was noted after connection of the third biological drug – etanercept, treatment with which had to be interrupted due to pregnancy planning. The return to the combined treatment after childbirth did not lead to repeated “success”. A positive result was achieved 12 weeks after tofacitinib at a dose of 10 mg/day, which provided a decrease in RA activity to moderate and complete withdrawal of glucocorticoids. Given the incomplete clinical effect, tofacitinib dose was increased to 20 mg/day by the outpatient rheumatologist, which resulted in achieving low RA activity persisting for 5 years. The second case demonstrates the effectiveness of tofacitinib inclusion in the RA treatment regimen as a “second-line” drug. A patient (age 46 years, RA duration 10 years) with long-term drug (methotrexate 25 mg/week) clinical and laboratory remission of RA after an upper respiratory tract infection developed an exacerbation of the disease. Despite three-component therapy with baseline anti-inflammatory drugs, the patient had persistence of high RA activity, which led to the revision of pathogenetic therapy – tofacitinib at a dose of 10 mg/day with clinical effect of the drug after 4 weeks. The achieved clinical and laboratory remission of the disease has been maintained for two years. In outpatient practice tofacitinib can be an effective tool for optimizing RA treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.