Pharmacotherapy For Rheumatoid Arthritis Research Articles

A review on potential adverse effects associated with Janus-kinase inhibitors

Rheumatoid arthritis (RA) is a chronic, symmetrical, inflammatory autoimmune disease that affects small joints. RA has a population prevalence of 0.5% to 1% in the U.S. The annual cost of care for chronic treatment of RA in the United States is estimated at $12,509. Pharmaceutical companies have developed drugs to treat RA using Janus kinase (JAK) inhibitors. These drugs can have potential adverse effects. Forecasting a better output to JAK inhibitors (JAKI’s). Therapy duration of JAKI’s and Problems regarding to strategies of dose reduction or if the discontinuation of therapy takes place in case of low disease activity. The accurate pharmacological profile and interactions of other drugs with JAKI’s have to establish. Proper safety, efficacy profile of JAKI’s and when administered in combination with DMARD’s. The safety, efficacy data of JAKI’s when compared to non-anti-TNF biologics. Obtaining of experience on JAKI’s that were already existed in the market and further experimental findings on newer compounds and which may clarify many of the aspects which are to be solved in nearer future as these JAKI will have greater application in treatment of RA. Regardless of significant developments in latest years in the pharmacotherapy of RA in the use of JAK inhibitors, yet the adverse effects of JAK inhibitors are unanswered. Therefore, one of the main concerns associated with JAK inhibitor is the potential adverse effects. The challenges can be addressed by clinical pharmacist mediated interventions related to dosing of JAK inhibitors and proper management of adverse drug reactions (ADRs).

Disease-Modifying Medications in Patients with Rheumatoid Arthritis in the USA: Trends from 2016 to 2021.

Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from <25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~1%) compared to biologics only (~17%) or biologics+MTX (~10%). About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low.

Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration-once again, in the summer population (the whole group-r = -0.64; treatment subgroups-r = -0.82 for LEF and -0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20-30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA.

The use of methotrexate in rheumatoid arthritis. Recommendations of the All-Russian public organization “Association of Rheumatologists of Russia”

Rheumatoid arthritis (RA) is the most frequent immunoinflammatory (autoimmune) rheumatic disease characterized by chronic erosive arthritis and systemic damage to internal organs. The data obtained in the course of basic research on deciphering the mechanisms of action of methotrexate (MT) and the materials of numerous randomized placebocontrolled trials, observational studies and national registries have strengthened the position of MT as the “gold standard” of RA pharmacotherapy and a key component of the “Treatment to Target” strategy. This was the basis for the development of new recommendations of the Association of Rheumatologists of Russia (ARR) concerning the use of MT in RA, according to which MT is considered as the drug of “choice” for induction and maintenance of remission in patients with early and advanced RA, including those who need combination therapy of MT with glucocorticoids, standard Disease-Modifying Antirheumatic Drugs (DMARDs), biologics and targeted synthetic DMARDs. Special attention is paid to the safety of MT therapy and the impact of MT on comorbid pathology associated with cardiovascular complications and interstitial lung disease. Implementation of the ARR recommendations into clinical practice will reduce the risk of disability and improve life prognosis in patients with RA.

Simulation-Based Research on Phytoconstituents of Embelia ribes Targeting Proteins with Pathophysiological Implications in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a heterogeneous inflammatory disease with an autoimmune origin and an incompletely elucidated pathophysiological mechanism. RA pharmacotherapy is based on chemically or biologically active substances that provide clinical alleviation and remission, but the disease is still incurable. As a result, there remains a need for significant therapeutic development, and adjuvant therapies may play an essential role in the search for novel RA treatment strategies. The aim of the present study was to investigate potential phytocompounds and phytocompound derivates as RA treatment agents, using in silico methodologies. In this regard, five phytoconstituents identified in different structures of Embelia ribes were evaluated by in silico methods for their potential action on target proteins of therapeutic interest in RA. The methodology involved identifying the phytocompound with the highest binding toward the target protein via molecular docking using AutoDock Vina 1.5.7, followed by a ligand-based virtual screening based on the structure of the most promising phytocompound using SwissSimilarity. This process led to the identification of ligands that are not currently utilized in medical practice, but that might have the potential to be used in the management of RA after further extensive experimental endorsements. ZINC000004024651 showed the highest binding affinity for the Bruton's tyrosine kinase protein, followed by ZINC000000434197 for p38 mitogen-activated protein kinases, ZINC000087606977 for interleukin-1 receptor-associated kinase 4, and ZINC000014728393 for matrix metallopeptidase 9, the latter two showing higher affinity than the co-crystallized compound. The relatively high affinities to target proteins and the pharmacokinetic data obtained by in silico studies using SwisADME suggest a first step for the inclusion of promising new compounds in various more advanced studies, leading to the evaluation of efficacy and safety profiles.

The role of interleukin 17 in the pathogenesis of rheumatoid arthritis. Are there any prospects for the use of IL-17 inhibitors?

Rheumatoid arthritis (RA) is an immunoinflammatory rheumatic disease (IMRI) characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy in patients. Thanks to the progress in the study of the mechanisms of the development of the IVRI and industrial biotechnology, new anti-inflammatory drugs have been created, the use of which has significantly increased the effectiveness of the pharmacotherapy of RA. However, the possibilities of pharmacotherapy for RA are limited, since all genetically engineered biological drugs (GEBDs), regardless of the mechanism of action, have approximately the same effectiveness in achieving remission. It is believed that the relatively unsatisfactory results of RA therapy are due to the heterogeneity of the mechanisms of inflammation. and pain. The significance of the Th17 type of immune response in the pathogenesis of RA, the results of controlled studies of IL-17 inhibitors, and the advisability of further studying the effectiveness of these drugs in patients with certain RA phenotypes are discussed.

More than 10 years’ follow-up of the Swanson metacarpophalangeal joint arthroplasty for the rheumatoid hand

BackgroundIn recent years, advances in pharmacotherapy for rheumatoid arthritis have dramatically improved the control of disease activity. However, a significant number of patients still develop hand deformity and require surgical reconstruction. The objective of this study was to evaluate the long-term efficacy and drawbacks of the Swanson metacarpophalangeal joint arthroplasty for patients with rheumatoid arthritis over 10 years. MethodsClinical and radiological evaluations were performed for 87 joints of 29 hands in 27 patients who underwent metacarpophalangeal joint arthroplasty using the Swanson implant, and who were followed up for an average of 11.4 (10–14) years. ResultsThe number of operated tender and swollen metacarpophalangeal joints decreased from 24 (27.6%) and 28 (32.2%) to 1 (1.1%) and 2 (2.3%), respectively. The patients’ general health and disease activity score 28-erythrocyte sedimentation rate improved at the last survey. Mild recurrence of ulnar drift was observed, but the deformity was generally well-corrected. Implant fracture was noted in eight joints (9.2%), and revision surgery was performed in two joints (2.3%). The average active range of extension/flexion changed from −46.3°/65.9° to −32.3°/56.6°. While a significant change was not noted in grip or pinch strength, patients were satisfied with the operation especially in terms of pain relief and improved hand appearance. ConclusionsThe long-term results of Swanson metacarpophalangeal joint arthroplasty were good in pain relief and correction of deformity, but some problems remain with regard to implant durability and mobility.

Consistency of recommendations for pharmacotherapy of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy. Recommendations for RA, specifically on pharmacotherapy, are essential in clinical practice. However, the direction and strength of recommendations are controversial across current clinical practice guidelines (CPGs) of RA. Objective: To systematically analyze the consistency of recommendations regarding pharmacotherapy of RA across CPGs. Methods: 11 electronic databases and websites were comprehensively searched from inception to 14 March 2022, to identify CPGs for diagnosis, therapy, and management of RA. Unambiguous and discrete specifications of the population-intervention-comparison (PIC) framework were used to classify the recommendations. Based on the PIC framework, consistency analyses across CPGs on pharmacotherapy of RA were performed. Two researchers reached a consensus on coding the direction and strength of each recommendation. Results: Finally, 26 CPGs were included in this study, and 14 of them, which included pharmacotherapy, were performed consistency analysis. 1) 64 recommendations from 14 CPGs were classified into 18 PICs. 2) Seven PICs (38%) were consistent in direction and strength, 10 PICs (56%) were consistent in direction but inconsistent in strength, and one PIC (6%) was inconsistent in direction (hydroxychloroquine, HCQ). 3) Sensitivity analysis tested the robustness, and the inconsistency remained high. Conclusion: The direction was highly consistent among the recommendations of pharmacotherapy for RA, but the strength was highly inconsistent. Reasons for the inconsistency need to be further investigated, and consistent recommendations could guide the pharmacotherapy of RA in clinical practice.

Autoimmune disorders and thyroid function in patients with rheumatoid arthritis after biological treatment

Rheumatoid arthritis (RA) and autoimmune diseases of the thyroid gland (AITD) often occur together. As autoimmune diseases, they share common pathological pathways, reflecting the fact that the treatment of the underlying disease can influence the course of thyroid disorders. The pharmacotherapy of RA is based on the supply of disease-modifying anti-inflammatory drugs with an increasing focus on biologics. This article aims to review the available literature describing the effects of biological treatments on thyroid function. The use of biological drugs may have the potential benefit of regulating the level of anti-thyroid antibodies. On the other hand, tumour necrosis factor-alpha (TNF-a) inhibitors are not indifferent to thyroid function and may increase the incidence of subacute thyroiditis. The coexistence of AITD and RA prompts consideration of the need for routine thyroid screening in RA patients and for RA screening in patients with thyroid disease who report joint problems.

In-depth bibliometric analysis and current scientific mapping research in the context of rheumatoid arthritis pharmacotherapy

Rheumatoid arthritis (RA) is a chronic multifactorial disorder of autoimmune etiology with a complex pathophysiological mechanism that is not yet fully elucidated. RA pharmacotherapy includes active molecules of chemical or biological nature that offer symptomatic relief and a slowing of progression, but still in a context of incurability. Therefore, the development of continuous research and multidisciplinary collaboration is essential. Although the management of RA is a topic of significant scientific relevance, existing bibliometric analyses are insufficient to assess this vast field. Consequently, the present study examines numerous manuscripts indexed in the Web of Science database using the VOSviewer software to provide through statistical interpretation of the data a comprehensive description of RA pharmacotherapy in terms of scientific impact, current state of research, number and frequency of citations, most prolific journals, authors, and countries, along with their relationships and other useful data for the literature search/publication process. Furthermore, the use of bubble maps of term occurrence has applicability in identifying current research trends in the field of RA pharmacotherapy as well as their evolution over the years. The leader in this field in terms of published papers is the United States, and the most prolific journal is Annals of the rheumatic diseases. The global management of RA, which is characterized by extensiveness and depth due to many variables, suggests the need for a conceptual framework based on pharmacotherapy coupled with comprehensive bibliometric studies, and the results may be useful for researchers in setting specific objectives that contribute to improving RA outcomes.

More than 20 years’ follow-up of metatarsal neck shortening oblique osteotomy for rheumatoid forefoot deformity

BackgroundIn recent years, advances in pharmacotherapy for rheumatoid arthritis (RA) have dramatically improved the control of disease activity. However, a significant number of patients still develop forefoot deformity. The purpose of this study was to investigate the results of more than 20 years’ follow-up of metatarsal neck shortening oblique osteotomy (SOO) for forefoot deformity in patients with RA. MethodsThe metatarsal neck SOO was performed on 163 feet in 108 patients between January 1985 and December 1996 in the authors’ hospital. For the patients, who met the survey criteria, an observational study was performed clinically and radiologically at the baseline and at more than 20 years after surgery. ResultsA retrospective cohort study was conducted on 36 feet in 22 patients, all of whom were female, and the mean age at surgery was 45.6 (35.0–63.0) years old. The follow-up period was 25.1 (21.0–31.0) years. The presence of painful callosities in the surgically treated feet without revised surgeries decreased from 32 feet (100%) to 4 feet (12.5%) at the last follow-up with mild pain that did not cause any footwear problems. Re-osteotomy at the metatarsal of the lessor toe was performed on four feet in two patients. Radiologically, among 128 toes without revised surgeries, 85% were able to have the joint space preserved, and 89% maintained a pain-free condition without any recurrence of deformity. The mean total Japanese Society for Surgery for the Foot (JSSF) RA foot and ankle score was 64.0/100, and the visual analogue scale (VAS) of overall satisfaction was 62 (0: dissatisfied, 100: highly satisfied). The overall satisfaction had a positive correlation with calcaneal pitch and negative correlation with joint space narrowing at the talocrural joint. ConclusionsMetatarsal neck SOO appeared to be effective for patients with RA. The deformity was corrected and retained for a long time.

Relationship of cytokine level dynamics with longterm results of early rheumatoid arthritis therapy

The aim of the work – to research the relationship between the dynamics of cytokine levels in the early period (the first 12 and 24 weeks) of pharmacotherapy for rheumatoid arthritis (RA) and long-term outcomes in patients with the disease.Material and methods. The analysis included 93 patients with early RA. The majority of patients were women (n=77), middle-aged (58 [49; 66] years), with an early stage of the disease (the duration of the disease is 7 [4–11.5] months), seropositive according to IgM rheumatoid factor and cyclic citrullinated peptide antibodies, who had high (59.7%) or moderate (38.8%) disease activity.The concentration of 27 cytokines in the blood serum was determined with the help of multiplex xMAP technology on the Bio-Plex array system analyzer (BIORAD, USA). Repeated clinical examination of patients was carried out after 6 years.Results. Patients who achieved remission/low disease activity SDAI after 6 years had a lower level of IL-6 (7.7 [7.4; 23.3]), IL-9 (13.5 [9.1; 18.9]) 12 weeks after the start of therapy; lower IL-9 level (12.6 [6.8; 16.2]) 24 weeks after the start of the treatment, compared with the group of patients with moderate and high inflammatory activity (23.5 [12.4; 69.5], 17.8 [15; 29] and 18.5 [14.2; 22.8] respectively).Findings. The assessment of the level of proinflammatory cytokines (IL-6, IL-17), immunoregulatory cytokine IL-9 allows to evaluate the activity of the disease more fully and identify a group of patients, who needs the therapy intensification.

β-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling Pathway.

Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that β-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear. Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining. Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2′-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression. Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.

Динаміка гострофазових показників у хворих на ревматоїдний артрит у поєднанні з абдомінальним ожирінням, цукровим діабетом типу 2 та артеріальною гіпертензією залежно від поліморфізму гена Т-786С eNOS під впливом лікування

Актуальність. Розробка сучасних підходів до фармакотерапії ревматоїдного артриту (РА) у поєднанні з абдомінальним ожирінням (АО), цукровим діабетом типу 2 (ЦД 2) та артеріальною гіпертензією (АГ) залишається актуальною на сьогодні. Мета. Дослідження динаміки гострофазових показників під впливом лікування хворих на РА у поєднанні з АО, ЦД 2 та АГ залежно від поліморфізму гена Т-786С ендотеліальної NO-синтази (eNOS). Матеріали та методи. Етап скринінгу пройшли 60 хворих на РА та 20 практично здорових осіб. Поліморфізм гена eNOS (rs2070744) визначали методом полімеразної ланцюгової реакції, а при оцінюванні ефективності лікування брали до уваги наявність коморбідної патології. Результати. Під впливом лікування вміст гострофазових показників запалення знизився: рівень С-реактивного білка у носіїв несприятливого СС-генотипу — на 30,74 % (р = 0,002), ТТ-генотипу — на 44,16 % та ТС-генотипу — на 32,21 % (р &lt; 0,001). Вміст ревматоїдного фактора зменшився у носіїв ТТ-генотипу на — 49,66 % (р &lt; 0,001), ТС-генотипу — на 26,46 % (р &lt; 0,001) та СС-генотипу — на 29,75 % (р &lt; 0,001). Рівень антитіл до циклічного цитрулінового пептиду знижувався лише серед носіїв ТТ-генотипу на 10,79 % (р &lt; 0,05). Вміст антистрептолізину-О вірогідно зменшився у носіїв Т-алелі на 14,07 і 21,44 %, без статистично значущої переваги у носіїв СС-генотипу (р &gt; 0,05). Рівні серомукоїду та сіалового тесту знизились у носіїв СС-генотипу на 19,52 % (р &lt; 0,05) і 24,56 % (р &lt; 0,05), у носіїв ТТ-генотипу — на 13,84 % (р &lt; 0,05) і 18,71 % (р &lt; 0,05) та ТС-генотипу — на 18,49 % (р &lt; 0,05) і 22,89 % (р &lt; 0,001) відповідно. Висновки. Після проведеного лікування зниження вмісту гострофазових показників запалення у носіїв ТТ-генотипу було найбільш суттєвим.

Neobvyklý případ systémové AA amyloidózy

An unusual case of AA amyloidosis is presented. Pharmacotherapy of rheumatoid arthritis induced its 5-year clinical remission, yet despite this, the patient developed AA amyloidosis. Amyloidosis involved the stomach, duodenum and kidneys. AA amyloidosis did not impair the renal functions significantly. This case emphasized the importance of non-targeted bio­psies of macroscopically normal mucosa of the stomach and duodenum that made it possible to dia­gnose amyloidosis. The patient remained without any gastrointestinal symptoms even during the subsequent follow-up. Key words: AA amyloidosis – gastroscopy – non-targeted bio­psies

PHARMACOECONOMIC APPROACHES FOR PHARMACOTHERAPY OF RHEUMATOID ARTHRITIS

Introduction. With the spread of the coronavirus pandemic, the role of pharmacotherapy of rheumatoid arthritis (RA) among patients with dual health disorders and in patients with systemic diseases is growing. This article is devoted to pharmacoeconomic for the pharmacotherapy of RA based on ABC/VEN analysis. Materials and methods. International and national medical and technological documents on standardization of medical care of RA, as well as scientific sources were used for regulatory, documentary and pharmacoeconomic analysis. ABC analysis was performed as a tool to study the cost of purchasing drugs. VEN analysis was performed to classify drugs into categories V, E and N on the principles of evidence-based medicine, forensic pharmacy, evidence-based pharmacy. Results. On the first stage of the research was conducted clinical and pharmacological analysis, the next stages - marketing and pharmacoeconomic analysis. Based on the ABC/VEN analysis, a matrix of the consolidated ABC/VEN analysis was developed. Discussion. The largest share (66.7 %) falls on the ATC classification code L "Antineoplastic and immunomodulatory agents". According to the results of marketing analysis tablets occupy 50 % of doctors' appointments; 75 % of the studied drugs have an unlimited validity of registration certificates. Ranking of country of origin of manufacturers of studied drugs: Germany – 37.6 %. Category A included five drugs’ INN (Mycophenolic acid, Azathioprine, Cyclophosphamide, Methotrexate, Ciclosporine), the cost of one dose is 5241.1 UAH, which is 78.12 % of the total cost of treatment for a patient with RA. It was found that six drugs INN (Methotrexate, Sulfasalazine, Hydroxychloroquine, Azathioprine, Ciclosporine, Cyclophosphamide) belong to category V (Vital). Conclusion. The introduction of information about pharmacoeconomic for pharmacotherapy of RA in the activities of health care institutions will ensure proper organization of the order of drug circulation at the stages of prescribing, prescribing, storage, accounting, quality control, transportation, release, destruction, licensing in accordance with current medical and pharmaceutical legislation.

AB0061 ALTERATIONS OF XANTHINE OXIDOREDUCTASE ACTIVITY IN RED BLOOD CELLS AFTER GLUCOCORTICOID TREATMENT IN RHEUMATOID ARTHRITIS

Background:According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical practice.Objectives:to evaluate the changes in activities of xanthine oxidoreductase interconvertible forms (xanthine oxidase, ЕС 1.17.3.2 and xanthine dehydrogenase, ЕС 1.17.1.4) in lysed red blood cells of RA patients in relation with glucocorticoid treatment.Methods:47 RA patients with verified RA and 30 healthy controls were enrolled in the study. The diagnosis was verified using the 2010 ACR/EULAR criteria 2010. All patients have moderate DAS28 scores. RA patients were randomized into 2 groups comparable in gender, age and the principal clinical manifestations. Methylprednisolone (Metipred, Orion Corp.), average dose 30 mg/day, and betamethasone (Diprospan, Schering-Plough), single dose7 mg, were administered intramuscularly in the respective groups. Хanthine oxidase (XO) and xanthine dehydrogenase (XDG) activities were measured in lysed red blood cells by spectrophotometric method as previously described [3]. The changes of these enzymes activities were studied in RA patients before and after the injection of glucocorticoids. Statistical comparison tests were selected in according to common guidelines, differences were considered significant when p&lt;0.05. Central tendencies were expressed as means±SEM.Results:Mean age of patients in methylprednisolone group was 41.8±1.05 years, and mean RA duration (± SEM) was 7.9±0.21 years. Mean age of patients in diprospan group was 40.9±1.07 years, and mean RA duration was 8.0±0.33 years. Significant decreases of XO activity and increase of XDG activity were observed in lysed red blood cells of RA patients just after the injection of each glucocorticoid drug. Changes of the enzymatic activities in lysed red blood cells were more pronounced in methylprednisolone group. However enzymatic activity did not reach the level of healthy controls. As described previously, decreased XO activity and increased XDG activity were observed in plasma of RA patients just after the injection of the average therapeutic doses of glucocorticoids, as well as in lysed lymphocytes just after the injection of methylprednisolone [4].Conclusion:Treatment with methylprednisolone and betamethasone can affect the balance of XO/XDG activity and increase the antioxidant potential of the blood. This effect can exert beneficial influence on autoimmune inflammation in RA.

Comparative analysis of the cost of pharmacotherapy schemes for patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is an unpredictable and progressive inflammatory disease of the joints of an immune nature, which in general for various reasons reduces the life expectancy of patients by 5 to 10 years. Pharmacotherapy of RA is based on long-term use of a large number of drugs of different pharmacotherapeutic groups, the cost of which varies significantly. The above makes the study of economic parameters of RA treatment an urgent problem.&#x0D; The aim of the study was to analyse the cost characteristics of pharmacotherapy of inpatients with RA in a hospital in order to optimize the cost of medication for these patients.&#x0D; The data of medical cards and medical records of 89 and 108 inpatients with RA, which were treated in the rheumatology department of the 4th Lviv City Clinical Hospital in 2009 and 2019, respectively, were selected as objects of the study. The methods of information retrieval, mathematical statistics, frequency, comparative, content analysis, data generalization, cost analysis were used.&#x0D; Disease-modifying antirheumatic drugs (DMARDs), glucocorticosteroids (GCs), and nonsteroidal anti-inflammatory drugs (NSAIDs) were grouped into six schemes for the RA pharmacotherapy in 2009 and 2019. An increase in the number of appointments of those schemes in which DMARDs were used has been established. The maximum share in both analysed periods was occupied by the triple pharmacotherapy scheme, which included all the above-mentioned drugs. This scheme was also the most expensive and its value at average retail prices (ARP) increased the most (9.4 times) from 2009 till 2019. During the analysed period, the average salary in Lviv region increased in 5.4 times, while the cost change indices (Ic) of different pharmacotherapy schemes, calculated on the basis of ARP, ranged from 6.9 for the two-component scheme with DMARDs and NSAIDs to 9.4 for the three-component scheme with DMARDs, GCs and NSAIDs. The analysis of affordability indices (Ia) showed that the most accessible was a two-component scheme, which included DMARDs and NSAIDs (Ia = 0.78). The study of the influence of the cost of the treatment schemes on the frequency of their prescribing using correlation analysis showed a very high dependence of these indices (R = 0.97). Pairwise correlations of pharmacotherapy appointment change indices (Iap) from Ic based on minimum (RPmin), maximum (RPmax) or average retail prices in Lviv pharmacies made it possible to establish a very high pair dependence of Iap from Ic calculated only on the basis of RPmax or ARP (R = 0.90).&#x0D; Thus, the analysis of patients' consumption of drugs for pharmacotherapy RA in the hospital allowed us to establish that in 2019 the treatment of RA became less available in comparison to 2009.

Functional Evaluation of Anti-TNF-α Affibody Molecules in Biochemical Detection and Inhibition to Signalling Pathways of a Synovial Cell.

An affibody molecule obtained from a bioengineered staphylococcal protein was previously shown to act as an affinity binder for a wide range of targets and develop Tumour Necrosis Factor α (TNF-α)-binding clones. In this study, we demonstrated that affibody molecules against TNF-α could bind to recombinant TNF-α on the membrane for biochemical detection. In addition, we examined whether the affibody molecules could block binding between recombinant TNF-α and its receptor on MH7A synovial cells. When a TNF-α-binding affibody was added, the production level of inflammatory mediators IL-6 and MMP-3 in MH7A were found to decrease up to 44%. Additionally, proliferation of synovial cells was also inhibited by the addition of TNF-α to cultivation media. These results suggest that affibody molecules against TNF-α could be candidate molecules for the detection of TNF-α during biochemical analysis and pharmacotherapy for rheumatoid arthritis.

THE PREVALENCE OF TRADITIONAL CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND IN THOSE WITH PSORIATIC ARTHRITIS

Objective: to comparatively analyze and estimate the prevalence of traditional cardiovascular risk factors (RFs) and the blood lipid spectrum in patients with rheumatoid arthritis (RA) and in those with psoriatic arthritis (PsA). Subjects and methods. The investigation enrolled 48 patients (41 females and 7 males) (mean age, 51.3±4.3 years) with RA who fulfilled the 1987 American College of Rheumatology (ACR) criteria and 46 patients (25 females and 21 males) (mean age, 49.6±3.8 years) with PsA fulfilling the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR) criteria who were treated in Dushanbe City Medical Center (CMC) Two in 2012 to 2019. The traditional and disease-related RFs of cardiovascular events (CVEs) were analyzed to identify the total cardiovascular risk using the SCORE and 2010 SCORE/EULAR scales; duplex scanning of the carotid arteries was performed to measure intima-media thickness and to identify atherosclerotic plaques; the blood lipid spectrum (total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol (HDLC)). The atherogenic index (TC-HDLC/HDLC) was calculated to determine the ratio of atherogenic to antiatherogenic lipoproteins. Results and discussion. The most common RFs for CVEs in the examined patients with RA and in those with PsA were hypertension (64.5 and 58.6%, respectively) and dyslipidemia (58.2 and 69.2%). It was found that systemic inflammation and pharmacotherapy for RA and PsA were actively involved in the formation of an atherogenic lipid profile and that the incidence of CVEs increased in patients with RA and in those with PsA who had two or more traditional and the so-called disease-related RFs. Conclusion . Our findings suggest that the development and progression of a wide range of CVEs in patients with RA and in those with PsA are based on the cumulative effect and complex interaction of chronic systemic autoimmune inflammation, traditional cardiovascular RFs, and long-term and uncontrolled use of nonsteroidal anti-inflammatory drugs and glucocorticoids, which assumes that CVEs have a multifactorial nature in RA and PsA.