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Introduction. The use of tofacitinib as a pharmacological treatment for rheumatoid arthritis remains relevant in the light of the predicted increase in prevalence of the disease. At the same time, due to the withdrawal of several foreign pharmaceutical companies from the Russian pharmaceutical market, there has been a heightened demand for domestically produced medications, including generic formulations of tofacitinib. Registration of generic drugs necessitates the conduct of bioanalytical studies. Development and validation of a method for quantifying the analyte in biosamples remains to be a crucial part of the bioequivalence studies.Aim. The aim of this research is to develop and validate a method for the quantitative determination of tofacitinib in human plasma using high-performance liquid chromatography as the separation system coupled with a tandem mass spectrometer for detection purposes.Materials and methods. Biosample preparation was based on plasma proteins precipitation using acetonitrile. Baricitinib was selected as an internal standard. The analytical range of the method was 1.00 to 200.00 ng/mL and was further expanded to 0.30 to 200.00 ng/mL during the analytical phase of the study. The mobile phase consisted of water and acetonitrile, both acidified with formic acid (0.1 % v/v). The stationary phase was a Phenomenex Kinetex C18 column [100 × 3.0 mm, with a particle size of 5 µm (Phenomenex, USA)]. Sample separation and detection were carried out using high-performance liquid chromatography coupled with a tandem mass spectrometry (HPLC-MS/MS), operating in positive ion mode. The multiple reaction monitoring (MRM) transitions selected for the analyte and the internal standard were 313.30 to 173.00 m/z and 371.90 to 186.00 m/z, respectively.Results and discussion. The developed assay was validated in accordance with the current requirements of regulatory documentation from the EAEU (Eurasian Economic Union), FDA (US Food and Drug Administration), and EMA (European Medicines Agency) with the following parameters being evaluated: selectivity, specificity, carry-over, matrix effect, recovery, calibration curve, lower limit of quantitation, accuracy, precision, stability. The validated method was applied in the analytical part of a bioequivalence study of domestically produced generic tofacitinib.Conclusion. A method for the quantitative determination of tofacitinib in human blood plasma with an analytical range of 0.30–200.00 ng/mL was developed and validated. Application of the assay during the analytical phase of bioequivalence study of generic tofacitinib confirms the possibility of using the method in similar bioanalytical investigations.

Introduction: JAK inhibitors are used in the treatment of psoriatic arthritis when there is a lack of effective response or intolerance to first-line drugs or their use must be discontinued due to the presence of side effects. JAK inhibitors inhibit the JAK-STAT signaling pathway which plays a significant role in the pathogenesis of many inflammatory and autoimmune diseases. This mechanism leads to a reduction in the level of pro-inflammatory cytokines which causes rapid improvement in the patient's clinical condition. Tofacitinib is the best-known drug in this group; its use carries an increased risk of cardiovascular events and reactivation of the varicella-zoster virus. Regular monitoring of patients results in faster detection of the first signs of undesirable effects and the cessation of their progression. The drug's safety profile is acceptable and the benefits outweigh possible complications. Aim of the study: The aim of the study is to summarize the available knowledge about tofacitinib treatment in psoriatic arthritis. The way of work, effectiveness of treatment and potential side effects were summarized and described. Materials and methods: The literature available in PubMed database was reviewed using the following keywords: “Psoriatic arthritis”, “Tofacitinib”, “JAK inhibitors”, “JAK-STAT” Conclusion: Tofacitinib treatment in rheumatology is used in psoriatic arthritis. The rapid improvement in the clinical condition of patients treated with JAK inhibitors is due to their direct impact on the modulation of the pathogenesis of the disease. The predictable benefits of therapy outweigh the side effects which can be detected at an early stage with regular monitoring of the patient.

Evaluation of the reasons for discontinuation of therapy with Janus kinase inhibitors (JAKi) may provide a clue to their more effective use.Objective : to analyze the survival of tofacitinib (TOFA) therapy and the reasons for its discontinuation in rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The study included 30 adult patients with RA hospitalized to the V.A. Nasonova Research Institute of Rheumatology from 2018 to 2020 for the biologic disease modifying antirheumatic drugs (bDMARDs) or JAKi treatment. Patients were followed up for 3 years or until treatment with TOFA was discontinued, whichever occurred first.Results and discussion. TOFA was prescribed as the first line therapy in 3 patients. In all these patients, the drug was discontinued for the following reasons: insufficient efficacy (IE) after 2 full years of treatment; adverse reaction (AR); administrative reasons (AdR), i.e. the inability to continue therapy due to the lack of drug supply at the place of residence. 11 patients received TOFA as the second line therapy, in 8 of them the treatment was interrupted: in 4 due to IE, in 3 due to AR (skin allergy) and in 1 due to AdR one year after its initiation. TOFA was prescribed as a third line therapy in 9 patients, in 2 of them the drug was discontinued due to IE and in 3 due to AR (allergic dermatitis in 2, dyspepsia in 1). Another 1 patient refused treatment due to a planned pregnancy. 6 patients received TOFA as the fourth line therapy, 5 of them (83.3%) continued to receive it for more than 3 years. In 1 patient, TOFA was discontinued after 1 month due to the dry cough and shortness of breath onset. In another 1 patient who was prescribed TOFA as the fifth line therapy, treatment was discontinued due to AR (recurrent Herpes zoster).Conclusion. As the results of the study show, no relationship was found between the incidence of AR or IE and clinical and demographic indicators, as well as the frequency of TOFA withdrawal and the line of therapy. At the same time, the shortest duration of retention on TOFA therapy was noted when it was prescribed as a first-line drug.

The effectiveness of personalized therapy for rheumatoid arthritis (RA) is associated with the correct choice of the drug and the ability to predict its effect before starting the treatment.Objective: to study in patients with RA the relationship between results of therapy and initial expression of genes responsible for bone and articular cartilage resorption (matrix metalloproteinase 9 – MMP9, – cathepsin K) and inflammation (tumor necrosis factor α – TNFα – and interleukin 1β – IL1β) in mononuclear cells of peripheral blood (PBMC), cultured with tofacitinib (TOFA).Patients and methods. We examined 12 patients with RA who had not previously received TOFA. The average age of the patients was 51 years, the average duration of the disease was 37.6 months. After 3 months of TOFA therapy, 6 patients achieved remission, while the rest had high and moderate disease activity. PBMC were isolated before therapy using a Ficoll density gradient and cultured in the presence of 100 nM TOFA for 48 h. Total RNA obtained from these cells was used to analyze the expression of MMP9, cathepsin K, IL1β, and TNFα genes using a real-time quantitative reverse transcription polymerase chain reaction.Results and discussion. TOFA is able to modify gene expression in cultured PBMC from RA patients compared to control cells. The initial expression of all the studied genes was significantly increased in cultured with TOFA cells of patients with persistent high and moderate disease activity during therapy, while TNFα gene expression was significantly reduced in patients who achieved remission.Conclusion. In patients with RA who have not previously received TOFA, a decrease in TNFα gene expression in blood cells cultured with this drug before the start of therapy may be a prognostic biomarker for achieving remission during TOFA therapy.

Objective – to study the effect of tofacitinib (TOFA) on Patient-Reported Outcomes (PROs) in psoriatic arthritis (PsA) patients (pts) activity in real clinical practice.Material and methods. Included 41 patients, predominantly men (58.9%), with a reliable diagnosis of psoriatic arthritis (PsA) according to the CASPAR criteria (2006), and signed informed consent to participate in the study. Mean age – 43.0±10.1 years, PsA duration – 18.6±10.4 years, psoriasis duration – 7.7±7.1 years, disease activity according to DAPSA (Disease Activity in Psoriatic Arthritis) – 44.2±17. At the initial visit, after 3 and 6 months, all patients underwent a standard rheumatological examination. The tender joint number (TJN) out of 68, the swollen joints number (SJN) out of 66 were evaluated, the DAPSA index was calculated, C-reactive protein (CRP, mg/dL), ESR (mm/h), patients with enthesitis and dactylitis in %. The prevalence and severity of psoriasis was determined by BSA (Body Surface Area). Among PROs, the severity of joint pain and disease activity were assessed according to the patient’s opinion of patient global assessment (PtGA) and pain using the visual analogue scale VAS (0–100 mm, respectively), HAQ, RAPID-3, DLQI, PsAID-12. All patients included in the study were prescribed TOFA 5 mg twice a day, followed by a possible increase in the dose to 10 mg twice a day. Also, after 3 and 6 months from the start of therapy, the PASS index (Patient-Acceptable Symptom State) was evaluated, i. e. symptom score below which the patient considers himself healthy, which corresponds to a total PsAID-12 score˂ 4 points and minimal clinically significant improvement (MCID, Minimal Clinical Improvement Disease – change in total PsAID-12 by 3 points).Results. In the whole group, DAPSA was 44.2±17.1, most patients (87.8%) had high PsA activity. By month 3/6 of follow-up, DAPSA significantly decreased to 15.2±12.4/11.8±9.4 (for all p

Despite great advances in the diagnosis and treatment of Immune-mediated inflammatory diseases (IMIDs), which have led to a significant improvement in the prognosis in many patients, the central medical problems of this pathology – restoring the quality of life and reducing mortality to the population level – are far from being resolved. This served as a powerful stimulus for the study of new approaches to the pharmacotherapy of IMIDs, one of which is associated with the discovery of targets for small-molecule therapeutics that inhibit intracellular “signaling” molecules JAKs (Janus kinases). The current achievements, trends and recommendations regarding the use of JAK inhibitors in the treatment of IMIDs and also in the hyper-response phase of COVID-19 are reviewed.

The article presents an analysis of literature data on the use of a new group of targeted synthetic disease-modifying antirheumatic drugs (DMARDs) Janus kinase (JAK) inhibitors – tofacitinib (TOFA) and upadacitinib (UPA) – in psoriatic arthritis (PsA). The results of randomized placebocontrolled clinical trials and long-term observational studies indicate the high efficacy and safety of using TOFA and UPA in the treatment of patients with PsA who are resistant to synthetic DMARDs and tumor necrosis factor-α inhibitors. The information obtained so far allows us to recommend JAK inhibitors as a new pathogenetic approach to the treatment of PsA.

A fundamentally important task of modern pharmacotherapy of immunoinflammatory diseases (IID) is a significant improvement in the quality of life (QOL) of patients, the fastest and most complete elimination of the most unpleasant manifestations of the disease, restoration of function and working capacity. Specialists in the therapy of various IID took part in panel dedicated to the discussion of this problem: Professor E.L. Nasonov, PhD., member of the Academy of Science; Professor A.M. Lila, PhD; V.N. Amirjanova, PhD; A.E. Karateev, PhD; T.V. Korotaeva, PhD; O.V. Knyazev, PhD; T.A. Lisitsyna, PhD; M.M Hobeish, PhD; E.S. Filatova. PhD.One of the central issues was the discussion of the need to use the patient's reported outcomes (PROs) indicator in analyzing the results of IID therapy (rheumatoid arthritis, psoriatic arthritis, psoriasis and inflammatory bowel disease). The need for its use is due to the fact that the principal goal of treatment with modern disease modifying antirheumatic drugs (DMARDs) is not only to achieve low activity or remission of IID, but also to maximize the general condition and QOL of patients. Therefore, such manifestations of IID as pain, fatigue, dysfunction, depression and anxiety, etc., must be analyzed in the course of treatment. The development of these symptoms is determined by the main immunopathological process and is associated, among others, with systemic overproduction of a number of pro-inflammatory cytokines. Modern DMARDs: Janus kinase (JAK) inhibitors, in particular tofacitinib, are capable of directly blocking the effect of cytokines on cells (suppressing the intracellular JAK / STAT signaling pathway), quickly and effectively eliminating pain, fatigue and dysfunction. The use of JAK inhibitors seems to be especially appropriate in patients with IID with high inflammatory activity and severe clinical manifestations.

Introduction. Tofacitinib is the first member of a new class of targeted synthetic anti-inflammatory drugs for the treatment of ulcerative colitis (UC). The article presents a three-year Russian experience of tofacitinib use for the treatment of moderate and severe UC.Aim of the study. To evaluate the efficacy and safety of tofacitinib therapy in real clinical practice in moderate to severe UC patients during three years of follow-up. Methods. The study included 56 patients with UC who had moderate (60.7%) and severe (35.8%) states of disease, the total lesion was diagnosed in 67.8%, and extraintestinal manifestations in 57.1% of patients. Early achievement of clinical response, clinical and endoscopic, corticosteroid-free remission, and safety were evaluated.Results. Early response to tofacitinib therapy was obtained in 47 (83.9%) patients. Clinical remission was achieved in 36 (64.3%) at week 8 of therapy and clinical response was achieved in 13 (23.2%) patients. The majority of patients who achieved clinical remission at weeks 8 and 12 achieved healing of colon mucosa at week 24. Clinical and endoscopic remission rates after 24 weeks – 44 (78.6%) patients, clinical response in 7 (12.5%) patients, 5 (8.9%) did not respond to TFCB therapy. Corticosteroidfree remission was 77.6%. After 2 years of tofacitinib therapy, remission of UC was maintained in 46 (82.1%). After 36 months, remission of UC was maintained in 45 (80.3%) of the 56 patients who had been started on tofacitinib therapy. The cumulative effect of survival in the treatment of tofacitinib in UC was 87.5% after 6 months and persisted for one year, 82.1% after 2 years, and 80.3% after 3 years.Conclusions. The administration of tofacitinib in UC is effective in achieving rapid clinical response, clinical remission, and mucosal healing in patients who do not respond well to biological therapy.

Axial involvement in psoriatic arthritis is quite common. There is no data on the use of tofacitinib, an oral Janus kinase inhibitor, in psoriatic arthritis patients with axial involvement, nor is there any data on its effect on active MRI sacroiliitis.The aim of the study was to assess the effect of tofacitinib therapy on the dynamics of active MRI sacroiliitis in psoriatic arthritis patients.Materials and methods. 41 patients with active psoriatic arthritis fulfilling the CASPAR criteria were included. Median age was 41.0 [34; 50] years old, median disease duration was 6.0 [3; 10] years. Apart from a standard clinical examination, 40 patients underwent sacroiliac joint MRI on scanner Siemens General Electric 1.5 TESLA. Bone marrow edema on MRI (STIR) with one lesion on two consecutive slices or at least two lesions on a single slice, was considered active MRI sacroiliitis. Tofacitinib was given in 5 mg tablets twice a day with a possible dose increase up to 10 mg twice a day after 12 weeks of therapy. At the end of study, over a period of 24 weeks, sacroiliac joint MRI examination was repeated in 35 patients.Results. Prior to tofacitinib therapy, active MRI sacroiliitis was detected in 14 of 40 (35%) patients: bilateral – in 9 patients, unilateral – in 5 patients. At the end of 24 weeks therapy, active MRI sacroiliitis was detected in 4 of 35 (11.4%) patients observed: in 1 patient with baseline bilateral MRI sacroiliitis and in 2 patients with unilateral MRI sacroiliitis. 1 patient showed negative dynamics, that is, development of active MRI sacroiliitis (absent at baseline). The decrease in number of active MRI sacroiliitis patients is statistically significant (p=0.017). At baseline, inflammatory changes were detected in 23 of 80 (28.8%) sacroiliac joints, after 24 weeks of therapy they were found in 5 of 70 (7.1%; p=0.001) sacroiliac joints observed. During the treatment period, there was a significant decrease in the initially high activity of spondylitis. After 24 weeks of treatment, median BASDAI decreased from 6.0 [4.2; 7.0] to 1.4 [0.6; 3.2], median ASDAS-CRP from 3.8 [2.8; 4.4] to 1.5 [1.0; 2.1] (p=0.001 for both comparisons). Prior to tofacitinib therapy, high activity according to BASDAI was observed in 90.2% of patients, low activity – in 9.8%; at the end of study – in 13.5% and 86.5% of patients, respectively (p=0.001). At baseline, very high activity by ASDAS-CRP was detected in 61% of patients, high activity – in 29.2%, low activity – in 9.8% of patients. At the end of study there weren’t any patients with very high activity by ASDAS-CRP (p=0.001), high activity remained in 23.1%, moderate and low activity – in 30.7% and 46.2% of patients, respectively (p=0.001 for both comparisons). Significant differences between baseline symptoms in patients with MRI sacroiliitis and without it were defined by number of digits with dactylitis – 2 [0; 4] and 0 [0; 2] (p=0.04) and by ESR values – 47 [26; 76] and 20 [6; 37] mm/h (p=0.02). These parameters were higher in MRI sacroiliitis subgroup. By the end of study, these differences leveled out: the number of digits with dactylitis decreased to 0 [0; 0] and 0 [0; 0] (р=0.48), ESR – to 12 [6; 16] and 8 [6; 16] mm/h, respectively (p=0.78).Conclusion. Tofacitinib therapy shows high efficacy in reducing active MRI sacroiliitis and decreasing activity of axial involvement in psoriatic arthritis patients. The use of tofacitinib in patients with active MRI sacroiliitis as well as dactylitis and increased ESR levels demonstrated its high efficacy.

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.

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL). Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA. Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated. Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not.

Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of >18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p

The design of targeted oral anti-inflammatory drugs, such as Janus kinase (JAK) inhibitors, the first representative of which is tofacitinib (TOFA), is considered a major achievement in biology and medicine early in the 21st century. Part I of the review considers the materials of studies evaluating the efficacy and safety of TOFA in rheumatoid arthritis (RA). The expansion of ideas about the mechanisms of development and chronicity of inflammation and the antiinflammatory and immunomodulatory effects of TOFA using a RA model has created theoretical and clinical prerequisites for studying the efficacy of TOFA in other immune-mediated inflammatory rheumatic diseases (IMIRDs) and chronic inflammatory non-rheumatic diseases. Part II of the review summarizes new data that allow one to formulate main areas of further clinical and fundamental studies, the objective of which is to expand indications for and to personalize therapy with JAK inhibitors in patients with IMIRDs.

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IIRDs) and designing a wide range of biological agents (BAs) are the major achievements of 21st century medicine. A new promising area of pharmacotherapy for IIRDs is associated with the design of so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors, called jakinibs. The first representative of the class of JAK inhibitors is tofacitinib (TOFA), which has been registered for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis. The review (Part I) presents new data on the efficacy and safety of TOFA in RA and discusses the role of TOFA in the treatment of RA as part of the treat-to-target strategy and new EULAR recommendations. Part II of the review will provide data on the use of TOFA in other IIRDs.

The JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the study was to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods. The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results. The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI>40), 15.9% had NCP (PainDETECT>18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p

Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight

Blockade of interleukin-6 (IL-6) is one of the most promising areas in the treatment of a number of immunoinflammatory diseases. Tocilizumab (TCZ), the first registered anti-IL-6 receptor monoclonal antibody, has been used effectively by rheumatologists since 2010. During this period, the spectrum of adverse reactions (ARs) of TCZ has been clearly defined. However, the multifaceted biological effects of IL-6 determine the probability of unexpected ARs. The article describes a clinical case of drug-induced encephalopathy with cognitive dysfunction during TCZ therapy.

Objective: to analyze the efficacy of tofacitinib (TOFA) in patients with an advanced stage of rheumatoid arthritis (RA) and previous methotrexate (MTX) failure according to comprehensive clinical and laboratory examination.Patients and methods. Nineteen patients (11 women and 8 men aged 29 to 71 years (mean age 53.47±10.53 years)) with a reliable diagnosis of RA according to the 2012 American College of Rheumatology (ACR) criteria were followed up. Due to a high disease activity (DAS28 averaged 5.84±0.89), the patients were prescribed TOFA 10 mg/day taken for 12 months. The disease activity indicators were assessed at baseline, 3, 6, and 12 months after the start of the study.Results and discussion. The effect of TOFA developed quite quickly: at 3 months of therapy, there were positive clinical, laboratory, and instrumental changes in most patients; 5 (26.3%) patients achieved the goal of treatment. At 12 months of therapy, 8 patients achieved DAS28 remission and 3 patients had a low disease activity; moderate RA activity persisted in 7 patients; and a high disease activity was seen in 1 patient; these SDAI activity indicators were observed in 2, 8, 7, and 2 patients, respectively. According to the ACR criteria, 20, 50, and 70% improvements were achieved by 8, 6, and 3 patients, respectively. No serious adverse reactions were recorded. The findings confirm the good efficacy and safety of TOFA in the treatment of patients with an advanced stage of RA.Conclusion. The innovative mechanism of TOFA allows a significant number of patients, in whom MTX therapy was not effective enough, to achieve the goal of treatment.

Chronic pain is one of the main manifestations of immuno-inflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which determines the severity of suffering, reduced quality of life and disability of patients. Unfortunately, the use of synthetic and biological disease modifying antirheumatic drugs, as well as non-steroidal anti-inflammatory drugs does not always provide sufficient control of pain in IIRD, even when it is possible to achieve a significant reduction in inflammatory activity. The reason for this is the complex mechanism of chronic pain. It includes not onlystimulation of pain receptors caused by damage of the elements of the musculoskeletal system, but also a change in the perception of pain associated with the phenomenon of central sensitization (CS). CS is characterized by a significant and persistent increase in the sensitivity of nociceptive neurons to pain and nonpain stimuli. One of the main theories of the CS development consider this phenomenon as an inflammatory reaction of the neuronenvironmentthe activation of astrocytes and microglial cells, local hyperproduction of cytokines, inflammatory mediators and neurotrophic factors. Factors contributing to the development of CS in IIRD are obesity, depression and anxiety, damage of the somatosensory system, insufficient relief of pain in the onset of the disease. Clinical manifestations of CS in IIRD is hyperalgesia, allodinia, «expanded pain» and secondary fibromyalgia. An important role in the development of chronic pain and CS plays the intracellular inflammatory pathway JAK-STAT. Therefore, JAK inhibitors, such as tofacitinib, used in RA and PsA, can also be considered as an effective means of controlling chronic pain in these diseases.

The article presents the data of international and domestic controlled studies, in which the effectiveness of topacitinib in the period of 6-24 months is evaluated in respect of clinical and laboratory manifestations of RA activity, progression of destructive arthritis and functional ability of rheumatoid arthritis patients. Also the data of efficiency and safety of tofacitinib in long terms - up to 96 months - are given. According to the results of short- and long-term studies, tofacitinib is a highly effective drug for the treatment of patients with active RA who have not responded to standard therapy with UCVD and GIBP. Tofacitinib is also highly effective in monotherapy. Tolerability of the drug is comparable with other variants of RA treatment.

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.

Major advances in pharmacology of the 21st century include the development of a new class of drugs, which are low-molecular, chemically synthesized molecules (the so-called "small molecules"), the point of application of which is Janus kinase (Janus kinase, JAK) involved in intracellular cytokine signaling. The review examines the molecular aspects of the JAK-STAT signaling pathway, justifying the use of the JAK-kinase inhibitor (tofacitinib) in the treatment of inflammatory bowel disease.

Objective: to compare the clinical efficacy in real clinical practice of the targeted synthetic disease-modifying antirheumatic drug (sDMARD) tofacitinib (TOFA) and the biologic DMARD (bDMARD), an inhibitor of tumor necrosis factor alpha (TNFα), adalimumab (ADA) in patients with psoriatic arthritis (PsA), included in the Russian nationwide register of patients with PsA.Patients and methods. The study included 77 patients with PsA (43 men and 34 women) who met the CASPAR criteria and were observed in the Russian nationwide register. Patients were divided into two groups depending on the treatment. Group 1, in which oral TOFA was prescribed, 5 mg 2 times a day, included 41 patients: 24 (58.5%) men and 17 (41.5%) women, the median age was 41 [34; 50] years, the median duration of PsA was 72 [35; 120] months. Group 2, in which subcutaneous ADA was used, 40 mg every 2 weeks, included 36 patients: 19 (52.8%) men and 17 (47.2%) women, the median age was 44 [34; 51] years, the median duration of PsA was 59 [22; 102] months. Combination therapy, including methotrexate (MT), received 80.5% of patients in the TOFA group and 52.8% of patients in the ADA group. At the beginning of the study and every 6 months further, the activity and efficacy of PsA therapy were assessed in all patients according to DAPSA and criteria for minimal disease activity – MDA (number of painful joints ≤1, number of swollen joints ≤1, PASI ≤1 or BSA ≤3 , pain score ≤15, patient's general assessment of disease activity ≤20 mm on a visual analogue scale, HAQ ≤0.5, enthesitis ≤1), dynamics of BASDAI and BSA were also assessed. The number of patients who achieved remission (DAPSA ≤4) or MDA (5 criteria out of 7) during therapy with TOFA and ADA was determined.Results and discussion. Before the start of the therapy in the 1st group, the median DAPSA was 44.2 [37.8; 55.3]: moderate PsA activity was in 5 (12.2%) patients, high in 36 (87.8%) patients. In group 2, the median DAPSA was 35.8 [21.1; 52]: low activity was detected in 3 (8.6%), moderate – in 11 (31.4%), high – in 21 (60%) patients (data from 35 patients was available). 6 months after the start of treatment in patients of the 1st and the 2nd group, there was a significant decrease in all indicators of PsA activity compared to the baseline. The median DAPSA was 11 [4.3; 17.3] and 9.1 [6; 19.6]; remissions according to DAPSA reached 11 (26.8%) and 6 (20.8%) patients, respectively, low activity – 15 (36.6%) and 13 (44.8%), MDA – 16 (40%) and 9 (30%). The number of patients with dactylitis in the 1st and in the 2nd group significantly decreased: from 22 (53.7%) to 5 (13.2%) and from 13 (36.1%) to 6 (20%), respectively. Median HAQ decreased from 1 [0.625; 1.5] to 0.5 [0; 0.875] and from 0.875 [0.5; 1.38] to 0.5 [0; 0.875]; median BASDAI – from 6 [4.2; 7] to 1.4 [0.6; 3.2] and from 4.4 [1.9; 5.8] to 3 [0.8; 4.5], respectively. In group 1, the number of patients with BSA> 3% decreased from 16 (39%) to 8 (26.7%; p

Objective: to determine the efficiency and safety of therapy with tofacitinib (TOFA) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) after insufficient previous therapy in real clinical practice.Subjects and methods. The investigation enrolled a total of 33 patients with RA who met the 1987 American College of Rheumatology (ACR) and/or the 2010 ACR/European League Against Rheumatism (EULAR) criteria. All the patients received TOFA 5–10 mg administered orally twice daily in combination with MTX; 30 patients took TOFA 10 mg/day and 3 patients had TOFA 20 mg/day. Every 6 weeks, the patients were examined by a rheumatologist and laboratory-instrumental tests. RA activity changes were assessed with DAS28-CRP, SDAI, and CDAI.Results and discussion. Results were assessed at weeks 12, 54, and 114. A significant decrease in DAS28-CRP, SDAI, and CDAI values was noted just at 12-week follow-up; at week 54, the mean values of these indices were 3.7±1.0, 14.9±8.8, and 13.4±9.0, respectively. There was a substantial decline in the levels of rheumatoid factor in 27% of the patients; while one third of them had a 60% decrease in its level and four patients achieved a negative seroconversion. Neither serious adverse events (AEs) no AEs that had not previously been described in the literature were observed during the follow-up study. Nine non-serious AEs were recorded in 8 (25.0%) patients.Conclusion. The investigation shows that TOFA makes it possible to control the activity of the inflammatory process and, with its sufficient safety and generally good tolerance, to achieve low RA activity in 49% of cases, including patients with multidrug resistance. The high efficacy of TOFA and, in particular, its combination with MTX used in patients with refractory RA give grounds for wider use of this drug, as confirmed by our investigation.

Objective: to evaluate the efficacy of tocilizumab (TCZ) versus tofacitinib (TOFA) in patients with severe and moderate rheumatoid arthritis (RA) who have not previously received methotrexate (MTX). Material and methods. A systematic search for studies dealing with the evaluation of the efficacy of TCZ and TOFA was made in accordance with the provisions of the instruction «Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)». Indirect comparison of two Function and ORAL Start randomized clinical trials was done, as described by Н.C. Buchera. The trials were comparable in their design and in the baseline characteristics of patients. The efficiency of pharmacotherapy for early RA was evaluated based on the ACR20/50/70 response rates in MTX-naive patients from three endpoints. Results. The indirect comparison of TOFA and TCZ (A MTX general control) after 52 weeks of treatment in MT-naive patients with severe and moderate RA indicated that the use of TOFA 5 mg twice daily and TCZ 8 mg/kg showed no difference in ACR20, ACR50, and ACR70 response rates. Nevertheless, there was a tendency to the greater efficiency of TOFA (5 mg twice daily) than that of TCZ (8 mg/kg). The indirect comparison of TOFA (10 mg twice daily) and TCZ (8 mg/kg) established that TCZ therapy was associated with the lower response rate for ACR50 (by 37%): the relative risk (RR) was 0.63; 95% confidence interval (CI), 0.44–0.90 and for ACR70 (by 51%): RR, 0.49; 95% CI, 0.29–0.83 as compared with TOFA therapy. Conclusion. The indirect comparisons confirmed that monotherapy with TOFA (10 mg twice daily) produced a more pronounced antiinflammatory effect than that with TCZ in MTX-naive patients with early severe and moderate RA of less than one year's duration. There were no statistically significant differences in ACR response rates between the TOFA (5 mg twice daily) and TCZ (8 mg/kg) groups.

The article tells about the results of an open 6-month clinical trial of the innovative drug tofacitinib (trade name Jakvinus), the first oral janus kinase inhibitor, in the treatment of 15 patients with rheumatoid arthritis who failed previous therapy. The study found that a daily dose of 10 mg of tofacitinib (TOFA) has high therapeutic efficacy and good tolerability. TOFA monotherapy (7 patients) and combination treatment with standard baseline medicines such as methotrexate or leflunomide (8 patients) was associated with a significant decrease in mean values of all the analyzed indices of RA activity (DAS28, CDAI, SDAI, RAPID), and a significant clinical improvement of ACR 20/50/70 criteria. The positive dynamics of the basic clinical parameters defining the severity of articular syndrome was combined with decreased levels of immune-inflammatory markers: C-reactive protein and rheumatoid factor in blood, and even resulted in seroconversion in two patients. No critical side effects requiring withdrawal or administration of complementary therapy for managing adverse events were observed in the studied group. The findings allowed to conclude that tofacitinib monotherapy and its combination with traditional disease-modifying drugs enhances RA therapy and thus can be recommended for the treatment of RA after failure of standard baseline therapies or contraindications to their use.

Objective. To perform health economic evaluation of several antirheumatic drugs in patients with rheumatoid arthritis (RA) progressed after DMARDs.Materials and methods. Three consequent line of rheumatoid arthritis therapy in patients progressed after methotrexate were modeled in Russian economic conditions. Markov modelling and CEA accounting for direct medical costs were used. The effectiveness criteria of RA treatment were: patient-years in remission and patient-years in low disease activity. We compared 12 different treatment regimens of second, third and fourth therapy line in patients progressed after methotrexate.Results. The health economic analysis of different RA treatment regimen after progression on methotrexate showed that evaluated regimens do not differs in terms of effectiveness and safety. At the mean time the model account for the patients compliance and showed that the maximum number of patient-years in remission can be reached with etanercept and tofacitinib treatment. Moreover, above mentioned combination in comparison to adalimumab and infliximab showed the positive budget impact.Conclusion. The choice of etanercept and tofacitinib in case of similar economics should be done accounting for individual patient features.

Tofacitinib (TOFA), a member of a new class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), is a promising medication for the treatment of rheumatoid arthritis (RA) and other immunoinflammatory diseases. The paper describes the Russian experi-ence with TOFA used to treat severe RA.Patients and methods. 101 RA patients (18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months) who were positive for rheumatoid factor (89.1%) and anti-cyclic citrullinated peptide antibodies (74.7%) and resistant to therapy with synthetic DMARDs (sDMARDs) (80.2%) and biological agents (19.8%) were given TOFA at a dose of 5 mg twice daily, which could be doubled if necessary. TOFA was used alone (n=9) or in combination with methotrexate (MT) (n=75) or other sDMARDs (n=17). The achievement of low disease activity (LDA) and clinical remission at 3 and 6 months of treatment by DAS28-ESR SDAI, and CDAI scores, and the indices of safety and tolerability were assessed.Results. A total of 93 (92.1%) of the 101 patients completed a 24-week period of the investigation. 8 (7.9%) patients prematurely discontinued TOFA after an average of 2.75±0.71 months. At the end of the study, the patients achieved the primary endpoint (LDA including remission) in terms of DAS28-ESR ≤3.2 (34.7%), SDAI ≤11 (47.5%), and CDAI ≤10 (48.5%) and the secondary endpoints (clinical remission) in terms of DAS28-ESR ≤2.6 (17.8%), SDAI ≤3.3 (8.9%), and CDAI ≤2.8 (6.9%). When TOFA was combined with MT, the discontinuation rate for the former was significantly lower (2.7%) than when TOFA was used in combination with other sDMARDs (29.4%) or alone (11.1%; p

Despite the advances in the therapy of rheumatoid arthritis (RA), which are associated with the use of biological anti-rheumatic drugs, the problemof effective treatment of RA is not still solved. Inclusion of new methods in treatment strategies, in particular the so-called «small molecules», i.e. synthetic compounds acting on intracellular signaling pathways, such as Tofacitinib (TOFA) approved for use in rheumatologic practice, is very important.Objective: to evaluate the efficacy and safety of therapy with TOFA in combination with synthetic disease-modifying anti-rheumatic drugs (s-DMARDs), primarily methotrexate (MTX) in in patients with active RA in real clinical practice.Subjects and methods. This ongoing open-label trial is a part of the scientific program «Russian Investigation of Methotrexate and Biologics in Early Active Inflammatory Arthritis» (REMARCA) that explores the possibility of adapting the «treat-to-target» strategy in real prac-tice in Russia. The study included RA patients with moderate to high disease activity despite treatment with MTX or other DMARDs. A total of 41 patients with RA were included (8 males, 33 females; mean age 52.6±14.2 years, disease duration 47.2±49.7 months, 82.9% RF+ and 80.5% anti-CCP+,DAS28-ESR 5.45±0.95, SDAI 30.2±12.2). All the patients had previously received s-DMARDs; 12 (29.3%) patients also had biological DMARDs (1 to 4 biologics). Oral TOFA 5 mg in combination with MTX or leflunomide was administered twice daily to 40 and 1 patients, respectively, with the possibility of increasing the dose up to 10 mg BID. To date, 37 and 12 patients received TOFA for 3 and 6 months, respectively.Results. TOFA was used as a second-line drug (after s-DMARDs failure) in 29 (70.7%), as a third line drug (after s-DMARDs and biologics failure) in 12 (29.3%) patients. The dose was escalated to 10 mg BID in 13 (31.2%) patients, on the average, 11.2±1.7 weeks after treatment initiation. TOFA was not discontinued in the reporting period. There was a significant reduction in disease activity following just 4 weeks of TOFA therapy. At 3 months, 27% of patients achieved low disease activity (LDA) by the SDAI; 29.7% had SDAI remission; 35% had HAQ ≤0.5; at 6 months, LDA, SDAI remission, had HAQ ≤0.5 were seen in 41.7, 41.7, and 67%, respectively. There were no significant differences in the suppression of RA activity depending on whether second- or third-line TOFA therapy was performed. There were no serious adverse events (SAEs) or serious infections.Conclusions. Second- and third-line TOFA therapy allows the majority of patients to quickly achieve the T2T goals (56.7 and 83.4% of patients at 3 and 6 months, respectively), so the drug can be quite successfully «integrated» into the T2T strategy along with biologics. The drug effectively inhibits granulomatous inflammation (by the example of rheumatoid nodules) and shows a sufficient safety (no SAEs).

Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA) or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab), and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA), a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

The paper describes the occurrence of polyarteritis nodosa in a patient with rheumatoid arthritis during treatment with tofacitinib. It considers the reasons why this condition should be regarded as an unforeseen borderline paradoxical adverse reaction.

Tofacitinib (TOFA) was the first synthetic small molecule drug which was comparable with genetically engineered biological agents (GIBA) in terms of its therapeutic effect in rheumatoid arthritis (RA). Results of treatment of over 4 thousand RA patients showed that the most common adverse events were nasopharyngitis, upper respiratory infections and urinary tract infections, herpes, diarrhea, nausea, gastritis. Serious side effects were registered in 15.4% of patients, and serious infections in 4.5%. Opportunistic infections occurred in 0.6% of patients, half of which were cases of tuberculosis. Anemia, hemocytopenia, increased lipidemia, a mild temporary decrease in glomerular filtration rate and increased creatinemia were also recorded. There were no anaphylactic or other immediate reactions. TOFA administration results were not different from those after treatment with GIBA in terms of mortality, incidence of infections and cancer.

The Meeting of the Expert Council considered in detail the key aspects associated with the possible development of adverse reactions during therapy with tofacitinib (TOFA). Active discussion gave rise to a resolution that summarized the main facts concerning the safety of TOFA and gave practical recommendations for the screening and monitoring of infections, cardiovascular diseases and other key areas requiring that exclusive control should be exercised during this therapy. TOFA is the first drug from a new group of immunomodifying and anti-inflammatory drugs, intracellular kinase inhibitors. As of now, it is the only drug that belongs to a class of the so-called small molecules, which is approved for the treatment of rheumatoid arthritis in the Russian Federation and a number of other countries. TOFA is a low molecular weight drug for oral administration; however, its unique mechanism of action brings it close to that of biological agents. A broad spectrum of biological effects of TOFA and its potential effect on a number of important physiological processes demand for special attention to the safety of its therapy.

The Russian Federation has not got sufficient experience with tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) so far; in this connection, all follow-ups using this drug in real clinical practice are of particular interest.Objective: to evaluate the efficancy and safety of TOFA in an open-label noncomparative trial of RA patients who have failed to achieve low disease activity or remission in compliance with the EULAR criteria after standard disease-modifying therapy and who have been previously untreated with drugs from a group of biological agents.Subjects and methods. Five patients (4 women and 1 men, whose age was 45 to 58 years (mean age 53 years)) with a valid diagnosis of RA were followed up. All the patients had an advanced clinical stage of RA with erosive arthritis (X-ray Stage III), predominantly involving the minor hand joints. Seropositive and seronegative (for rheumatoid factor (RF)) RA was diagnosed in 4 and 1 patients, respectively. At the inclusion into the study, the patients received disease-modifying antirheumatic drugs. Due to the remaining disease activity, all the patients were given TOFA in a dose of 5 mg twice daily (10 mg/day); moreover, 4 patients received its monotherapy (1 because of intolerability and 3 because of noncompliance); 1 female patient took a combination of TOFA and methotrexate (MT) in a dose of 10 mg/week. Two patients continued to use methylprednisolone 4 mg/day (that had been long taken) in combination with TOFA. The duration of TOFA therapy was 3 months.Results. TOFA 10 mg/day showed high therapeutic efficacy and good tolerability. Three-month disease-modifying therapy with TOFA(4 patients) and its combination with MT (1 patient) resulted in a considerable reduction in DAS28 scores and a significant clinical improvement in ACR 20/50/70 responses. Positive clinical changes were associated with a reduction in the blood level of immune markers (C-reactive protein and RF) up to the seroconversion phenomenon in one female patient.Conclusion. The findings allow TOFA to be recommended for the treatment of RA in case of the inefficiency of standard disease-modifying agents or contraindications to their use.

One of the breakthroughs in pharmacology of the XXI century is the development of a new class of drugs, which are low molecular weight (

The article tells about the applicability of tyrosine kinase inhibitors in the treatment of rheumatoid arthritis (RA). The first drug from the new subgroup of targeted disease-modifying synthetic anti-inflammatory drugs is in focus - the oral inhibitor of Janus kinase Tofacitinib. There are results of ORAL START, ORAL SOLO and ORAL STEP studies which evaluated tofacitinib in three categories of patients: those who didn't undergo methotrexate (MTX) treatment in the past; patients without response to MT and other disease modifying anti-rheumatic drugs (DMARDs); patients with insufficient response to TNF-alpha inhibitors. The results show that Tofacitinib can be indicated either after failure of DMARD therapy and genetically engineered biologic drugs, or can be used as first-line therapy in RA. According to the author, Tofacitinib is a very promising medication which can become an essential element of the active treatment strategy for RA patients to achieve clinical remission. Nevertheless, further research is needed, as well as records of practical outcomes of the drug use.