BARICITINIB: NEW PHARMACOTHERAPY OPTIONS FOR RHEUMATOID ARTHRITIS AND OTHER IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES

2020 ◽  
Vol 58 (3) ◽  
pp. 304-316
Author(s):  
E. L. Nasonov ◽  
A. M. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Janus Kinase ◽  
Inflammatory Rheumatic Diseases ◽  
Jak Inhibitors ◽  
Oral Medications ◽  
Immune Mediated ◽  
Wide Range ◽  
Promising Area ◽  
Medical Advances

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.

scholarly journals The progress of rheumatology in the 21st century potential uses of upadacitinib in rheumatoid arthritis and other inflammatory rheumatic diseases

2020 ◽  
Vol 58 (5) ◽  
pp. 532-543
Author(s):  
E. L. Nasonov ◽  
A. M. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Rheumatic Diseases ◽  
21St Century ◽  
Janus Kinase ◽  
Inflammatory Rheumatic Diseases ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Wide Range ◽  
Inflammatory Drugs

The explanation of the mechanisms underlying the pathogenesis of rheumatoid arthritis (RA), along with the development of a wide range of biologics (bDMARDs), is among the major achievements of medicine in the 21st century. A new direction in the pharmacotherapy of inflammatory rheumatic diseases is associated with the development of “targeted” oral anti-inflammatory drugs, which include Janus kinase (JAK) inhibitors. One representative of the class of JAK inhibitors is upadacitinib (UPA), which has been registered for the treatment of RA and is undergoing clinical studies in patients with ankylosing spondylitis, psoriatic arthritis, and other inflammatory rheumatic diseases. This review presents new data on the efficacy and safety of UPA in RA.

scholarly journals COVID-19 and immune-mediated inflammatory rheumatic diseases

2021 ◽  
Vol 30 (1) ◽  
pp. 24-29
Author(s):  
E.L. Nasonov
Keyword(s):  
Rheumatic Diseases ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Drug Repurposing ◽  
Medical Community ◽  
Inflammatory Rheumatic Diseases ◽  
Immune Disorders ◽  
Jak Inhibitors ◽  
Off Label ◽  
Immune Mediated

During the pandemics of COVID-19 associated with SARS-CoV-2, great attention in the medical community was devoted to the new clinical and basic issues of immune pathogenesis of human diseases. The detailed analysis of clinical signs and symptomes and immune disorders that occur in COVID-19 patients suggested that SARS-CoV-2 infection is associated with various extrapulmonary clinical manifestations and laboratory abnormalitites that are typical for immune-mediated rheumatic diseases. These data justified drug repurposing and the off-label administration of various medications specially designed for patients with immune-mediated rheumatic diseases for the treatment of COVID-19. The author reviews the prospects for administration of glucocorticoids, biologic agents, JAK inhibitors and other anti-cytokine agents in patients with COVID-19.

scholarly journals AB1280-HPR REQUIRED FORCE TO OBTAIN A POSITIVE SQUEEZE TEST AUTOMATIZED IN PATIENTS WITH HAND ARTHRALGIA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1931.3-1931
Author(s):  
M. M. Castañeda-Martínez ◽  
G. Figueroa-Parra ◽  
D. Vega-Morales ◽  
B. R. Vázquez Fuentes ◽  
Y. G. Ordoñez Azuara ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Rheumatic Diseases ◽  
Primary Care Physicians ◽  
Clinical Aspects ◽  
Inflammatory Rheumatic Diseases ◽  
Undifferentiated Arthritis ◽  
Left Hand ◽  
Hand Force ◽  
The Uk

Background:Primary care physicians (PCP) are usually the first contact of people with inflammatory rheumatic diseases, and find the early symptoms of Rheumatoid Arthritis (RA) difficult to distinguish from those of other rheumatic diseases. A time-delay in the reference to Rheumatology is a health issue in several countries. The clinical aspects that general practitioner took into account in hand arthralgia patients are important to make the reference. In particular the Squeeze Test (ST) - which is simple to perform and rapidly done, ST is useful for identifying progression to RA in patients with undifferentiated arthritis. The ST has been described as not reliable because is clinician-dependent.Objectives:To identify the required force that needs to be applied in order to obtain a positive Automatized Squeeze Test (AST) in a cohort of patients with hand arthralgia.Methods:Ninety-seven patients were recruited in Family Medicine Consultation and in Rheumatology Consultation of the Hospital Universitario “Dr. José Eleuterio González” in Monterrey, Nuevo León, México. Eligible patients were adults (aged≥18 years) with hand arthralgia (that wasn’t caused by trauma) as their chief complaint. After obtaining informed consent and after a questionnaire application, patients were submitted to AST maneuver, using an automated compressor with different forces already predetermined in the interface of the software used for compression.Results:In this cohort of 98 patients, 79 (80.6%) were women. The mean age was 51.14 years (SD 14.66). Ninety-six (97.9%) patients were right handed. The diagnoses were Osteoarthritis (OA) (16.3%), RA (5.1%), Undifferentiated arthritis (1.2%), Psoriatic arthritis (1.2%) and Fibromyalgia (2%). Force measures according to diagnoses are reported in Table 1.Table 1.Diagnoses and mean forcesDiagnosisn (%)Right hand force mean (kg/s2) (SD)Left hand force mean (kg/s2) (SD)OA16 (16.3)3.53 (2.74)3.18(2.73)RA5 (5.1)3.60 (2.53)3.16(1.36)UA1 (1.2)7.60(0)8.70(0)PsA1 (1.2)7.60(0)7.80(0)FM2 (2.0)4.11(4.40)1.75(1.06)OA, Osteoarthritis;RA, Rheumatoid Arthritis;UA, Undifferentiated Arthritis;PsA, Psoriatic Arthritis;FM, Fibromyalgia;SD, Standard DeviationConclusion:In the cases of RA and OA, the means of force to obtain a positive AST was lower than in the rest of the diagnoses.References:[1]Stack R, Nightingale P, Jinks C, Shaw K, Herron-Marx S, Horne R et al. Delays between the onset of symptoms and first rheumatology consultation in patients with rheumatoid arthritis in the UK: an observational study. BMJ Open. 2019;9(3):e024361.Disclosure of Interests:None declared

scholarly journals Update on the therapeutic management of patients with either psoriatic arthritis or ulcerative colitis: focus on the JAK inhibitor tofacitinib

2021 ◽  
Vol 13 ◽  
pp. 1759720X2097777
Author(s):  
Maria Sole Chimenti ◽  
Paola Conigliaro ◽  
Livia Biancone ◽  
Roberto Perricone
Keyword(s):  
Ulcerative Colitis ◽  
Psoriatic Arthritis ◽  
Janus Kinase ◽  
Phase Iii ◽  
Jak Inhibitors ◽  
Immune Mediated ◽  
Significant Burden ◽  
Phase Iii Trials ◽  
Disease Modifying Agents ◽  
Interleukin Inhibitors

Psoriatic arthritis (PsA) and ulcerative colitis (UC) are immune-mediated diseases that cause significant burden worldwide. Recent advances in their management have improved patient outcomes. However, significant unmet needs still remain as not all patients respond to current treatments, and patients may lose responsiveness over time. An improved understanding of the pathophysiology of these diseases has brought about the development of novel disease-modifying agents, including interleukin inhibitors and, more recently, Janus kinase (JAK) inhibitors. With the approval of tofacitinib for the treatment of adults with active PsA and in adult patients with moderately-to-severely active UC, JAK inhibitors have recently entered the treatment armamentarium for PsA and UC. A number of other JAK inhibitors are also undergoing clinical development and are currently in phase III trials. This review provides an overview of the current therapeutic options for PsA and UC, with a focus on the JAK inhibitors.

Ankylosing spondylitis, other spondyloarthritides, and related conditions

2010 ◽  
pp. 3603-3616 ◽  
Author(s):  
J. Braun ◽  
J. Sieper
Keyword(s):  
Rheumatoid Arthritis ◽  
Back Pain ◽  
Ankylosing Spondylitis ◽  
Gastrointestinal Tract ◽  
Rheumatic Diseases ◽  
Skin Lesions ◽  
Inflammatory Back Pain ◽  
Psoriatic Skin ◽  
Inflammatory Rheumatic Diseases ◽  
History Of

The spondyloarthritides are a group of inflammatory rheumatic diseases with predominant involvement of axial and peripheral joints and entheses, together with other characteristic clinical features, including inflammatory back pain, sacroiliitis, peripheral arthritis (mainly in the legs), enthesitis, dactylitis, preceding infection of the urogenital/gastrointestinal tract, psoriatic skin lesions, Crohn-like gut lesions, anterior uveitis, and a family history of Spondyloarthritis. They are the second most frequent inflammatory rheumatic diseases after rheumatoid arthritis....

scholarly journals Incidence of Tuberculosis in Inflammatory Rheumatic Diseases: Results from a Lithuanian Retrospective Cohort Study

Medicina ◽  
2020 ◽  
Vol 56 (8) ◽  
pp. 392
Author(s):  
Dalia Miltinienė ◽  
Giedrė Deresevičienė ◽  
Birutė Nakčerienė ◽  
Valerija Edita Davidavičienė ◽  
Edvardas Danila ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Incidence Rate ◽  
Rheumatic Diseases ◽  
Retrospective Cohort ◽  
Significant Risk ◽  
Inflammatory Rheumatic Diseases ◽  
The Mean ◽  
Rheumatic Patients

Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients’ population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Material and Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013–2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18–97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41–1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.

scholarly journals P460 Evaluation of potential mechanisms underlying the safety observations of filgotinib in clinical studies in rheumatoid arthritis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S409-S409
Author(s):  
A Clarke ◽  
J Di Paolo ◽  
B Downie ◽  
A Meng ◽  
N Mollova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Clinical Studies ◽  
Nk Cell ◽  
Janus Kinase ◽  
Jak Inhibitor ◽  
Jak Inhibitors ◽  
Erythroid Progenitor ◽  
Cell Counts

Abstract Background Inhibitors of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway have demonstrated efficacy in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Differences in selectivity of JAK inhibitors for JAK1, JAK2, JAK3 and TYK2 may influence their respective safety profiles, and the mechanisms responsible are not currently known. Filgotinib (FIL), a JAK1 inhibitor, did not negatively impact haemoglobin, LDL:HDL ratios or natural killer (NK) cell counts in clinical trials. Here, we compare the in vitro mechanistic profiles of four JAK inhibitors at clinically relevant doses. Methods JAK inhibitors (FIL, FIL metabolite [GS-829845], baricitinib [BARI], tofacitinib [TOFA], and upadacitinib [UPA]) were evaluated in vitro in human-cell-based assays. Growth of erythroid progenitors from human cord blood CD34+ cells was assessed using a HemaTox™ liquid expansion assay, NK cell proliferation was induced by IL-15 and LXR agonist-induced cholesteryl ester transfer protein (CETP) expression was assessed in the hepatic cell line, HepG2. Using assay-generated IC50 values and the reported human plasma concentrations from clinical studies, we calculated the target coverage for each JAK inhibitor at clinically relevant doses. The activity of FIL in humans was based on PK/PD modelling of FIL + GS-829845. Results Inhibition of cellular activity was calculated for each JAK inhibitor based on in vitro dose-response data, human exposure data and modelled PK/PD relationships. At clinically relevant doses, FIL resulted in lower calculated inhibition of NK cell proliferation compared with other JAK inhibitors. FIL 100 mg and 200 mg also reduced CETP expression, whereas other JAK inhibitors had no effect. There was no difference in the effect of FIL vs. other JAK inhibitors on erythroid progenitor cell differentiation or maturation. Conclusion FIL, a JAK1 inhibitor, resulted in less inhibition of NK cell proliferation compared with BARI, TOFA, and UPA. FIL also reduced LXR agonist-induced CETP expression, while the other inhibitors did not alter these levels. These results provide a potential mechanistic link between the observed reduction of CETP concentration following FIL treatment and the previously observed reduction in the LDL:HDL ratio in RA patients.

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