Strategy For Rheumatoid Arthritis Research Articles

Impact of age and cardiovascular risk factors on the incidence of adverse events in patients with rheumatoid arthritis treated with Janus Kinase inhibitors: data from a real-life multicentric cohort

Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs—including age—and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized.

Scanning Electron Microscopic Analysis of the Bone-Resorption Activity in Mature Osteoclasts.

Bone homeostasis depends on the balance between bone deposition and bone resorption, which are mediated by the activity of osteoblasts and osteoclasts, respectively. Blocking osteoclast activity can be a therapeutic strategy in rheumatoid arthritis (RA) to reduce subsequent bone erosion. Therefore, investigating the activity of osteoclasts is essential for understanding the pathology of RA. Bone-resorption pits, which are caused by activated osteoclasts, are significantly increased in RA. Scanning electron microscopic analysis of bone-resorption pits is an effective method for understanding the pathology of RA. This chapter describes the method for observing the surface microstructure of pit formation on bone slices.

The perspective of Polish patients with rheumatoid arthritis - treatment expectations, patient-reported outcomes, and digital literacy (the SENSE study).

A widely accepted treat-to-target strategy for rheumatoid arthritis (RA) requires the patient's perspective in making treatment decisions. However, data on treatment preferences and expectations of Polish patients with RA are scarce. The aim of the study was to determine the satisfaction with treatment and the nature of therapeutic preferences and expectations of Polish patients with moderate to severe RA. Fifty-two adult Polish patients with moderately to highly active RA were asked to complete patient-reported outcomes and patient-provided information questionnaires. Additionally, patient sociodemographic and clinical data and information on patient current and planned treatment strategies were collected. The mean global assessment of patient satisfaction with treatment was 64.1 ±24.6, below the level of indicating satisfaction. Rheumatoid arthritis negatively impacted patients' lives, resulting in a 37.8% impairment of work efficiency and 45% impairment of total activity. Primary treatment expectations for patients were lasting relief of RA symptoms, reduced pain and swelling in joints, increased flexibility of joints, and general improvement of arthritis. The most acceptable potential side effect was weight gain and the least acceptable were increases in the risk of cardiovascular disease, infection, and malignancies. The rapid onset of the drug effect (up to 1 week) was a preference of 48.1% of patients. Access to internet health resources was important for 44.2% of patients, but the median total eHealth literacy score in the study population was 24.0 (interquartile range: 20.5-28.0, range 8-37), which means low digital health literacy (DHL). Understanding these treatment preferences and expectations of patients with RA is essential for clinical practitioners to facilitate shared treatment decision-making. Digital health literacy data suggest the need of further improvement.

Understanding Heterogeneity in Patients’ Conceptualisation of Treatment for Rheumatoid Arthritis: A Cluster Analysis

ObjectiveUptake of treat-to-target (TTT) strategies for rheumatoid arthritis (RA) management is low. Our objective was to understand the heterogeneity in patients’ conceptualisation of RA treatment to inform interventions improving TTT...

New Targets and Strategies for Rheumatoid Arthritis: From Signal Transduction to Epigenetic Aspect.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and even permanent disability, seriously affecting patients' quality of life. At present, the complete cure for RA is not achievable, only to relieve the symptoms to reduce the pain of patients. Factors such as environment, genes, and sex can induce RA. Presently, non-steroidal anti-inflammatory drugs, DRMADs, and glucocorticoids are commonly used in treating RA. In recent years, some biological agents have also been applied in clinical practice, but most have side effects. Therefore, finding new mechanisms and targets for treating RA is necessary. This review summarizes some potential targets discovered from the perspective of epigenetics and RA mechanisms.

What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis

ObjectivesA treat-to-target (T2T) strategy has been shown to be superior to usual care in rheumatoid arthritis (RA), but the optimal target remains unknown. Targets are based on a disease activity...

Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study.

Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15-41] vs. 19 [5-30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.

Stabilization of UHRF1 in synovial fibroblasts is a novel therapeutic strategy for rheumatoid arthritis

Stabilization of UHRF1 in synovial fibroblasts is a novel therapeutic strategy for rheumatoid arthritis

Deep dive into achieving the therapeutic target: results from a prospective, 6‑month, observational study nested in routine rheumatoid arthritis care.

Achieving remission or lowdisease activity (LDA) is an integral principle of treat‑to‑target (T2T) strategy in rheumatoid arthritis (RA). Prior studies have reported that achieving T2T therapeutic goals may be realistic only for a fraction of patients. Prospective, real‑world data on achieving target disease control in ambulatory care populations are limited for Central and Eastern European countries. The aim of the study was to analyze the efficacy of treatment and determine simple predictors of achieving T2T therapy goals in daily RA practice. This multicenter, 6‑month study evaluated therapy outcomes and clinical characteristics of 791 consecutive RA outpatients, meeting the preset criteria of inadequate disease control. Only 9% of RA patients achieved remission or LAD after 3 months and 35% after 6 months. Achieving treatment targets after 6 months was associated with lower rates of pain, disability, presenteeism and absenteeism, which reflected improved quality of life. Provider views on adherence appeared discordant with patient claims, and did not predict target achievement. Never smoking, lower body mass index, and lower prednisone dose (<7.5 mg daily) were independently associated with a higher likelihood of achieving T2T therapeutic goals after 6 months. A combination of clinical characteristics and provider treatment decisions shapes the "profile" of a patient failing to achieve T2T goals. Low‑dose steroid equivalent, never smoking, and lower body mass index appear as individual characteristics independently associated with achieving LDA / remission at 3 and 6 months.

Towards a Better Implementation of Treat-to-Target Strategy in Rheumatoid Arthritis: A Comparison of Two Real-World Cohorts.

IntroductionTreat-to-target (T2T) strategy has been the core of rheumatoid arthritis (RA) management for over a decade, although it implementation has varied distinctly in real practices. We report here our investigation of the differences in disease activity and target achievement of two patient cohorts with different T2T implementations.MethodsData of the CENTRA (Collaboratively intENsive Treat-to-target in RA) and TARRA (Treat-to-TARget in RA) cohorts were used. The CENTRA cohort is a RA cohort prospectively followed up by a fixed team with tight control, while the TARRA is a longitudinal observational cohort followed up by a rheumatologist with casual control. Patients from the two cohorts were matched 1:3 by propensity score matching. The primary outcome was the Simplified Disease Activity Index (SDAI) at the 1-year follow-up.ResultsIncluded in this analysis were 102 patients from the CENTRA cohort and 271 patients from the TARRA cohort. Both groups were comparable in terms of age, gender, disease course, and seropositivity. At the end of the 1-year follow-up, the SDAI of patients in the CENTRA cohort was significantly lower than that of patients in the TARRA cohort (2.1 vs. 3.4; p < 0.001). A similar result was obtained based on the generalized estimating equation (GEE) model (p = 0.009). In addition, more patients in the CENTRA cohort achieved SDAI-defined remission compared to the TARRA cohort [72 (70.6%) vs. 134 (49.4%); p < 0.001].ConclusionPatients with RA may benefit more from a tight control T2T strategy with closer follow-up and appropriate education compared with those with a casual T2T strategy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00441-0.

MiRNAs as Biomarkers and Possible Therapeutic Strategies in Rheumatoid Arthritis.

Within the past years, more and more attention has been devoted to the epigenetic dysregulation that provides an additional window for understanding the possible mechanisms involved in the pathogenesis of autoimmune rheumatic diseases. Rheumatoid arthritis (RA) is a heterogeneous disease where a specific immunologic and genetic/epigenetic background is responsible for disease manifestations and course. In this field, microRNAs (miRNA; miR) are being identified as key regulators of immune cell development and function. The identification of disease-associated miRNAs will introduce us to the post-genomic era, providing the real probability of manipulating the genetic impact of autoimmune diseases. Thereby, different miRNAs may be good candidates for biomarkers in disease diagnosis, prognosis, treatment and other clinical applications. Here, we outline not only the role of miRNAs in immune and inflammatory responses in RA, but also present miRNAs as diagnostic/prognostic biomarkers. Research into miRNAs is still in its infancy; however, investigation into these novel biomarkers could progress the use of personalized medicine in RA treatment. Finally, we discussed the possibility of miRNA-based therapy in RA patients, which holds promise, given major advances in the therapy of patients with inflammatory arthritis.

The ideal mHealth-application for rheumatoid arthritis: qualitative findings from stakeholder focus groups

BackgroundShifts in treatment strategies for rheumatoid arthritis (RA) have made ambulatory care more labour-intensive. These developments have prompted innovative care models, including mobile health (mHealth) applications. This study aimed to explore the perceptions of mHealth-inexperienced stakeholders concerning these applications in RA care.MethodsWe performed a qualitative study by focus group interviews of stakeholders including RA patients, nurses specialised in RA care and rheumatologists. The qualitative analysis guide of Leuven (QUAGOL), which is based on grounded theory principles, was used to thematically analyse the data. In addition, the Persuasive Systems Design (PSD) model was used to structure recommended app-features.ResultsIn total, 2 focus groups with nurses (total n = 16), 2 with patients (n = 17) and 2 with rheumatologists (n = 25) took place. Six overarching themes emerged from the analysis. Efficiency of care and enabling patient empowerment were the two themes considered as expected benefits of mHealth-use in practice by the stakeholders. In contrast, 4 themes emerged as possible barriers of mHealth-use: the burden of chronic app-use, motivational aspects, target group aspects, and legal and organisational requirements. Additionally, recommendations for an ideal mHealth-app could be structured into 4 domains (Primary Task Support, Dialogue Support, Social Support and System Credibility) according to the PSD-framework. Most recommended features were related to improving ease of use (Task Support) and System Credibility.ConclusionsAlthough mHealth-apps were expected to improve care efficiency and stimulate patient empowerment, stakeholders were concerned that mHealth-app use could reinforce negative illness behaviour. For mHealth-apps to be successful in practice, challenges according to stakeholders were avoiding long-term poor compliance, finding the target audience and tailoring a legal and organisational framework. Finally, the ideal mHealth-application should above all be trustworthy and easy to use.

The Role of Sex, Perceived Pain, and Illness Perceptions in Disease Activity in Rheumatoid Arthritis

Background: In the “treating to target” strategy for Rheumatoid Arthritis (RA) management, “cognitive” beyond “physical” measures allow a more comprehensive assessment. Objective: This study reported a predictive analysis of patients on disease activity and the degree to which these predictions could be uniquely attributable to Illness Perception (IP), pain, and sex differences. Methods: This cross-sectional study was conducted on 108 patients with Rheumatoid Arthritis aged 18 to 65 years old, selected via convenience sampling. Measurements were done using Disease Activity Score in 28 Joints (DAS28), patient’s Illness Perception Questionnaire (IPQ-R), and Numerical Rating Scale (NRS) for perceived pain. Data were analyzed applying Spearman and Pearson correlation coefficients and Multiple Stepwise Regression (MSR). Results: In correlation analysis, the sex- Disease Activity association (0.40, P&lt;0.01) and Pain-Disease Activity association (0.54, P&lt;0.01) were found. Additionally, we observed stronger and significant associations between IPQ-R subscales and disease activity [Identity (r=0.53, P&lt;0.01) personal control (r=-0.40, P&lt;0.01) and emotional representation (r=0.36, P&lt;0.01)]. Regression analysis showed that sex differences were a not significant predictor and perceived pain and three IPQ-R items (identity, personal control, and emotional representation) emerged as the strongest predictors (P&lt;0.001). Conclusion: Disease activity was predicted by pain and three illness perception items. By identifying the components affecting Disease Activity, the therapist can adjust complementary treatment according to patients’ needs.

OP0189 MACROPHAGE PET/CT IMAGING OF THE FEET CAN CONTRIBUTE TO EARLY PREDICTION OF THERAPY OUTCOME IN RHEUMATOID ARTHRITIS

Background:Treat-to-target strategies for rheumatoid arthritis (RA) have shown significant improvements in therapy outcomes. Nevertheless, it usually takes a minimum of 12 weeks before clinical assessment of treatment response can be made. Quantitative positron emission tomography (PET) has shown potential to predict clinical response at a very early stage in the treatment in RA patients.(1) In particular, macrophage imaging by [11C]-(R)-PK11195 PET allows for highly sensitive and specific imaging of RA disease activity.(2,3)Objectives:To determine whether quantitative assessment using [11C]-(R)-PK11195 PET/CT imaging at 0-2 weeks is associated with subsequent clinical response to therapy with methotrexate and step-down prednisolone (COBRA-light) therapy in therapy-naive RA patients.Methods:Whole body [11C]-(R)-PK11195 PET/CT scans were performed at baseline and after two weeks of treatment in thirty-five clinically active and therapy-naive RA patients and at least two clinically inflamed joints. All patients were DMARD-naïve and received medication according to the COBRA-light schedule. (4) Clinical follow up with DAS44 assessment was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were visually assessed by two experienced readers blinded to clinical data and quantitatively analyzed using in-house software. Regions of interest (ROIs) with a fixed size per joint (on both visual PET positive and negative joints) were placed on shoulders, elbows, hips, knees and hand and feet joints, with the CT-scan as anatomical reference. Standardized uptake values (SUVs) normalized for body weight were calculated in these ROIs to determine the amount of tracer uptake per joint. SPSS version 22.0 was used to perform regression analyses. The sum of visually positive joints and the average SUV in hand joints, feet joints and all joints in the body were compared with DAS44 scores.Results:Included patients were mostly male (51%) and aged 54 ± 12. Baseline DAS44 was 3.2 ± 1.0; all but one of the thirty-five patients demonstrated visually enhanced tracer uptake in one or more joints on PET/CT. A total of 171 (out of 1470) joints (12%) were visually PET positive at baseline. Over 90% of PET positive sites were located either in the wrists (15%), small hand joints (37%), or small feet joints (40%; Figure 1A). After 2 weeks, the number of PET positive joints had decreased to 100, with the highest decrease in quantitative uptake in feet joints (Figure 1B). Notably, both visual and quantitative PET data at baseline and differences between baseline and 2 weeks did not correlate with DAS44 at 13 weeks (DAS44-13wks). However, at 2 weeks, the average SUV in the feet (SUVfeet-2wks) – but not average SUVhands-2wks or average SUVtotalbody-2wks – was significantly correlated with DAS44-13wks (R2 = 0.14, p = 0.04). DAS44-2wks and SUVfeet-2wks both contributed independent information to the prediction DAS44-13wks (combined R2 = 0.297, p &lt; 0.01).Figure 1.Changes in [11C]-(R)-PK11195 uptake in MTP joints of a RA patient, before (A) and 2 weeks after initiation of COBRA light treatment (B).Conclusion:Quantitative macrophage PET assessment in feet joints after 2 weeks of COBRA light treatment in early RA patients correlates with clinical response after 3 months of treatment. This correlation further increases when combined with the DAS44 score at 2 weeks. Therefore, quantitative, non-invasive macrophage PET/CT, especially when combined with early clinical assessment, may be useful for early assessment of response to treatment. Further studies will help optimize timing and focus of the PET examination in prediction of treatment response.

Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Damage.

Janus kinase inhibitors (JAKis) represent a new strategy in rheumatoid arthritis (RA) therapy. Still, data directly comparing different JAKis are rare. In the present in vitro study, we investigated the immunomodulatory potential of four JAKis (tofacitinib, baricitinib, upadacitinib, and filgotinib) currently approved for RA treatment by the European Medicines Agency. Increasing concentrations of JAKi or methotrexate, conventionally used in RA therapy, were either added to freshly mitogen-stimulated or preactivated peripheral blood mononuclear cells (PBMC), isolated from healthy volunteers. A comparable, dose-dependent inhibition of lymphocyte proliferation was observed in samples treated with tofacitinib, baricitinib, and upadacitinib, while dosage of filgotinib had to be two orders of magnitude higher. In contrast, antiproliferative effects were strongly attenuated when JAKi were added to preactivated PBMCs. High dosage of upadacitinib and filgotinib also affected cell viability. Further, analyses of DNA double-strand break markers γH2AX and 53BP1 indicated an enhanced level of DNA damage in cells incubated with high concentrations of filgotinib and a dose-dependent reduction in clearance of radiation-induced γH2AX foci in the presence of tofacitinib or baricitinib. Thereby, our study demonstrated a broad comparability of immunomodulatory effects induced by different JAKi and provided first indications, that (pan)JAKi may impair DNA damage repair in irradiated PBMCs.

A patient-centered knowledge translation tool for treat-to-target strategy in rheumatoid arthritis: Patient and rheumatologist perspectives.

Implementation of treat-to-target (T2T) for rheumatoid arthritis (RA) presents many challenges and an evidence-practice gap has emerged. This study assessed clinician and patient barriers to the implementation of an RA-T2T strategy and developed a knowledge translation (KT) tool for use in "real-life" clinical settings. Surveys of patients and rheumatologists measured agreement with RA-T2T recommendations and use in daily practice. Patient knowledge and perceptions were assessed as was clinician willingness to alter practice and barriers to RA-T2T using visual analog scales. An electronic KT-tool was developed and a two-phase usability trial undertaken to assess use in clinical interactions. Ninety-one percent of patients had no prior knowledge of RA-T2T but agreed with the recommendations showing mean level agreement scores (8.39-9.54, SD 2.37-1.54). Ninety percent were willing to try RA-T2T, 49% felt their treatment could be improved and 28% wanted more involvement in treatment decisions. Rheumatologists agreed with RA-T2T recommendations (7.30-9.27, SD 2.59-0.91). Barriers to implementation identified by rheumatologists included time, appointment availability and perceived patient reluctance to escalate medications. Usability experiences with the KT-tool were tracked and clinicians reported it was easy to use (100%), resulted in a discussion of RA-T2T (73%) and a target being set for 63% of consults. Patients reported they read (92%) and understood (87%) the information in the KT-tool, and that a target was set in 62% of interactions. RA-T2T uptake in clinical practice may be improved through understanding local clinician and patient barriers and an implementation strategy utilizing a patient-driven KT-tool.

Tuberculosis risk with biologics by screening-guided preventive strategy in rheumatoid arthritis under intermediate tuberculosis burden.

We aimed to compare tuberculosis (TB) risk during biologics treatment between patients with RA who did (prophylaxis) and did not (non-prophylaxis) undergo chemoprophylaxis following pre-biologic latent TB screening in Korea of an intermediate TB burden. Using the 2002-16 Korea National Health Insurance database, we conducted a cohort study examining TB risk, defined by International Classification of Diseases Tenth Revision codes plus anti-TB drugs, among RA patients initiating a biologic drug with and without chemoprophylaxis after screening triage for latent TB. To control baseline confounding, we used propensity score-based fine stratification (PSS) and weighting. Cox proportional hazards models estimated hazard ratios and 95% CIs comparing TB risk between the prophylaxis vs non-prophylaxis groups. The PSS-weighted study cohort (mean age 57.0 years; 81.3% female) included 2249 and 7225 RA patients in the prophylaxis and non-prophylaxis groups, respectively. During 2.42 years of biologics treatment, 118 patients developed TB with the incidence rate per 100 person-years of 0.33 in the prophylaxis and 0.63 in the non-prophylaxis groups. The PSS-weighted hazard ratio (95% CI) for TB associated with the prophylaxis was 0.52 (0.32, 0.86). During the follow-up time, the incidence rate of TB remained consistently low in the prophylaxis group but it was highest in the first year, then time-dependently declined in the non-prophylaxis group. This population-based cohort study warns that the current screening-based preventive strategy generates a substantially higher TB risk after biologics initiation among screening-negative patients compared with screening-positive patients receiving chemoprophylaxis, when the background TB burden is not low.

Implementation and Evaluation of Audit and Feedback for Monitoring Treat-to-Target (T2T) Strategies in Rheumatoid Arthritis Using Performance Measures.

IntroductionIn collaboration with the Alberta Medical Association’s Physician Learning Program we developed individualized physician reports and held a group feedback session on rheumatoid arthritis (RA) performance measures (PM) to facilitate treat-to-target (T2T) strategies and evaluated physician experiences with this process.Methods5 PMs addressing T2T concepts from an established Canadian quality framework were operationalized for physician practice reports at 2 university-affiliated rheumatology clinics. Rheum4U, a quality improvement and research platform, was the data source. The audit results were reviewed in a facilitated group feedback session. Rheumatologists provided experiential feedback on the process through survey and/or an interview. Transcripts from interviews were analyzed using a 6-step thematic analysis.Results11 of 12 eligible rheumatologists consented to receive practice reports and provided feedback through surveys (n = 5) and interviews (n = 6). The practice reports from Rheum4U (n = 448 patients) revealed high rates of yearly follow-up (> 85%, PM1) and 100% performance on documentation of disease activity at ≥ 50% of visits (PM2). Only 34% of patients were seen within 3 months if not in remission (PM3) with 62% (2017) and 69% (2018) of those with active RA achieving a LDA state within 6 months (PM4). Approximately 70% of patients were in remission at any time point (PM5). All survey respondents agreed or strongly agreed comparison to peers was valuable and helped them reflect on their practice. Several strategies for improvement were identified, including but not limited to, leveraging of electronic records for future audit and feedback reports, providing additional granularity of results, additional stratification of results, and using high-performing peers as the comparator rather than the group mean.ConclusionsAudit and feedback was perceived by clinicians as a useful strategy for evaluating T2T efforts in RA. Future work will focus on longitudinal evaluation of the clinical impact of this quality improvement initiative.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00237-0) contains supplementary material, which is available to authorized users.

Immunomodulatory drug therapy for the disease caused by SARS-CoV-2 infection (COVID-19)

This systematic review focuses on the state-of-the-art pharmacotherapy of immune disorders in the novel coronavirus infection (COVID-19), leading to a cytokine storm and uncontrolled inflammatory response that causes severe tissue damage and multiple organ failure. A lot of theoretical, experimental and clinical data support the need for immunomodulatory (immunosuppressive) therapy for this disease. It should be emphasized that all immunomodulatory drugs for COVID-19 are prescribed off label, and the evidence base of the results of randomized trials is just being accumulated. We review the immunomodulatory therapy for COVID-19 with the following agents: glucocorticoids, hydroxychloroquine and chloro-quine, type 1 interferons, interleukin-6 antagonists (tocilizumab, sarilumab, olokizumab), interleukin-1 p inhibitor canakinumab, tumour necrosis factor inhibitors (infliximab), Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, ruxolitinib), as well as drugs with other mechanisms of action (abatacept, nivolumab, tacrolimus, sirolimus, fingolimod, melphalan, cyclosporine, methotrexate). At the moment, the most reasonable is the use of interleukin-6 receptor inhibitors, intermediate and high dose glucocorticoids, and JAK inhibitors. Based on the latest data from clinical studies, especially the "Solidarity” trial, the use of hydroxychloroquine and chloroquine seems to have insufficient evidence. There are significant pathophysiological overlaps in the development of immunopathology in COVID-19 and in rheumatic diseases, and the strategy of early aggressive immunosuppressive therapy proposed by a number of researchers almost completely coincides with the current strategies for rheumatoid arthritis.

Two-year cost effectiveness between two gradual tapering strategies in rheumatoid arthritis: cost-utility analysis of the TARA trial

ObjectiveThe aim of the current study was to evaluate the 2-year cost-utility ratio between tapering conventional synthetic disease-modifying antirheumatic drugs (csDMARD) first followed by the tumour necrosis factor (TNF)-inhibitor, or...