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.

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 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 IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Milena Iwaszko ◽  
Joanna Wielińska ◽  
Jerzy Świerkot ◽  
Katarzyna Kolossa ◽  
Renata Sokolik ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Inflammatory Arthritis ◽  
Gene Polymorphisms ◽  
Disease Susceptibility ◽  
Tnf Inhibitors ◽  
Inflammatory Rheumatic Diseases

ObjectiveRheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients.Materials and MethodsIn total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays.ResultsIn the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS.ConclusionsThe obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.

scholarly journals AB0565 JAK INHIBITORS AND PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1319-1320
Author(s):  
F. Campanaro ◽  
A. Zaffaroni ◽  
A. Batticciotto ◽  
A. Cappelli ◽  
M. P. Donadini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Psoriatic Arthritis ◽  
Response Rate ◽  
Mean Difference ◽  
Janus Kinase ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Acr20 Response ◽  
Acr20 Response Rate

Background:Despite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, there is a huge necessity of finding effective drugs for this disease. JAK inhibitors (JAKi) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA (1). Up to now Tofacitinib is the only JAKi approved by the European Medicines Agency (EMA) for the treatment of PsA but in the next few years the number of approved JAKi is expected to rise significantly.Objectives:To assess the efficacy and safety of different JAKi for the treatment of PsA.Methods:A systematic review of the literature was performed to identify randomized controlled trials (RCTs), by electronic search of MEDLINE and EMBASE database until October 2020. Studies were considered eligible if they met the following criteria: I) study was a RCT; II) only patients with PsA were included; III) JAKi was compared to placebo in addition to the standard of care. Two reviewers (FC and AZ) performed study selection, with disagreements solved by the opinion of an expert reviewer (AS). The outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic.Results:We identified 557 potentially relevant studies. A total of 554 studies were excluded based on title and/or abstract screening. Three RCTs for a total of 947 PsA patients treated with JAKi were included (2,3,4). Two were phase III studies on the efficacy and safety of Tofacitinib (OPAL Beyond and OPAL Broaden) and one was a phase II study on Filgotinib (Equator). All three studies were judged at low risk of bias according to Cochrane criteria (5). The primary efficacy outcome in all the studies was the number of patients who achieved the response rate of the American College of Rheumatology 20 score (ACR20). The outcomes evaluation was performed at 12 week for the Filgotinib trial and at 16 week for the Tofacitinib trials. We used for the main analyses the group of patients randomized to Tofacitinib 5 mg because this is the only dosage approved by the EMA for the treatment of PsA. JAKi showed a significantly higher ACR20 response rate compared to placebo (OR 3.54, 95% CI 1.76 - 7.09, I^2 = 74%). JAKi also showed a significantly higher ACR50 response rate (OR 3.36, 95% CI 2.22 - 5.09, I^2 = 0%), ACR70 response rate (OR 2.82, 95% CI 1.67 - 4.76, I^2 = 20%), PsARC response rate (OR 2.67, 95% CI 1.26 - 5.65, I^2 = 79%), PASI75 response rate (OR 3.15, 95% CI 1.61 - 6.15, I^2 = 45%) compared to placebo. JAKi were also associated with significantly better HAQ-DI (mean difference -0.23 95% CI -0.31 - -0.14) and fatigue, measured with FACIT-F (mean difference 3.54 95% CI 2.13 - 4.94). JAKi compared to placebo were associated with a non-statistically significant different risk of serious adverse events (OR 0.56, 95% CI 0.11 - 2.91, I^2 = 38%).Conclusion:This is the first published systematic review that performed a comprehensive and simultaneous evaluation of the efficacy and safety of JAKi for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKi, that appears to be effective and safe over placebo. The impact of these data on international clinical guidelines needs further investigation.References:[1]George E Fragoulis, et al. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis, Rheumatology, Volume 58, Issue Supplement_1, February 2019, Pages i43–i54[2]Mease P, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 2017; 377: 1537-50.[3]Gladman D, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 2017; 377: 1525-36.[4]Mease P, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2367–77.[5]Higgins JP, et Al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560Figure 1.ACR20 response rate of Jaki over PlaceboDisclosure of Interests:None declared.

scholarly journals JANUS KINASE ENZYME (JAK) INHIBITORS AND RHEUMATOID ARTHRITIS: A REVIEW OF THE LITERATURE

2019 ◽  
pp. 11-14
Author(s):  
AYMAN ASKARI ◽  
ABDULLA KHALID NOURI ◽  
HANA MORRISSEY ◽  
PATRICK A. BALL
Keyword(s):  
Rheumatoid Arthritis ◽  
Normal Cell ◽  
Essential Role ◽  
Enzyme Inhibitors ◽  
Biologic Agents ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Review Of The Literature ◽  
Jak Inhibitors ◽  
Multiple Trials

Cytokines play an essential role in normal cell growth and the regulation of immune function. The emergence of Janus Kinase Enzyme inhibitors promises the start of a revolution in the treatment of several chronic diseases. Their efficacy and safety profile have been demonstrated in multiple trials and they have been licensed for the treatment of a number of diseases including RA and PsA. Moreover, the use of highly selective Janus Kinase Enzyme inhibitors is currently being studied aiming to reduce side effects compared with traditional JAKinibs, an example of that would be the recent FDA approved upadacitinib. The Janus Kinase Enzyme inhibitorsmay supplant the classical biologic agents in the treatment of autoimmune diseases, since they exhibitthe advantages of oral administration, simultaneous blockade of multiple cytokines, reversibility and the lack of immunogenicity.

scholarly journals Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2199956
Author(s):  
Chenghua Weng ◽  
Leixi Xue ◽  
Qing Wang ◽  
Wentian Lu ◽  
Jiajun Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Comparative Efficacy ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Objective: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). Methods: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire–Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. Results: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between −1.91 and −0.80) and HAQ-DI (WMDs ranging between −0.34 and −0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between −1.11 and −0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06–2.61] and rituximab (3.17, 1.11–10.80). Conclusions: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.

scholarly journals The role of targeted synthetic drugs in the treatment of rheumatic diseases: focus on tofacitinib

2020 ◽  
pp. 83-94
Author(s):  
D. E. Karateev ◽  
E. L. Luchikhina
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Kinase Inhibitors ◽  
Low Frequency ◽  
Signal Pathway ◽  
Inflammatory Rheumatic Diseases ◽  
Biologic Drugs ◽  
Low Disease Activity

The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).

scholarly journals SAT0372 PATIENTS WITH PSORIATIC ARTHRITIS SHOW HIGHER BONE DENSITY COMPARED TO AGE AND GENDER MATCHED PATIENTS WITH ANKYLOSING SPONDYLITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1133.2-1134
Author(s):  
D. Freier ◽  
E. Wiebe ◽  
R. Biesen ◽  
T. Buttgereit ◽  
S. Hermann ◽  
...  
Keyword(s):  
Back Pain ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Density ◽  
Rheumatic Diseases ◽  
Inflammatory Rheumatic Diseases ◽  
Age And Gender ◽  
Gender Distribution ◽  
Density Data ◽  
And Gender

Background:The prevalence of osteoporosis in inflammatory rheumatic diseases such as psoriatic arthritis (PsA) has not been sufficiently clarified yet, and the data in the literature are heterogeneous. In addition, it is still unclear to what extent patients with PsA differ in terms of bone density from patients with other forms of spondyloarthritis such as ankylosing spondylitis (AS).Objectives:In an interim analysis of the Rh-GIOP Study (ClinicalTrials.gov IdentifierNCT02719314), we observed that PsA patients demonstrated more frequently normal bone density than any other patient group analyzed (suffering from e.g. rheumatoid arthritis or systemic sclerosis). The main objective of this investigation was to compare bone density data from patients with PsA and AS, as both diseases belong to the spondyloarthritis group. 1100 patients with inflammatory rheumatic diseases provided the basis of Rh-GIOP, a prospective study monitoring glucocorticoid (GC)-induced osteoporosis in patients with rheumatic diseases. Rh-GIOP was established in 2015 at the Charité University Hospital. Bone mineral density data were measured by dual x-ray absorptiometry (DXA).Methods:92 patients with PsA (65% female) were compared with 51 patients suffering from AS (35% female). Potential risk and protective factors (e.g. data on GC treatment, anti-rheumatic therapy), laboratory parameters (e.g. Vitamin D, alkaline phosphatase, calcium and inflammatory markers) and functional status (e.g. Health Assessment Questionnaire, sporting activities, back pain) were compared between these groups. Statistical analysis was performed descriptively using mean and standard deviation, t-tests for metric variables, and chi-square tests for nominal variables. Due to the heterogeneous gender distribution, an additional statistical matching was performed to compare patients matched by age and gender.Results:Patients with PsA displayed significantly higher minimal T-scores than patients with AS (p=0.003) even though patients with AS were younger and more often male (p<0.001). AS patients showed a higher frequency of osteopenic bone densities (p<0.05), however, no differences in the frequency of osteoporotic bone densities were found. Body-mass-index (BMI) was significantly higher (p<0.001) in PsA patients. PsA patients demonstrated a higher frequency of csDMARD use (p<0.001). Additional analyses among PsA patients with and without csDMARDs revealed also significantly higher minimal T-scores in PsA patients taking csDMARDs (90% Methotrexate), and both groups showed the same average of age and gender distribution. Furthermore, AS patients complained significantly more often of back pain (96 % vs. 74%, p=0.001) than PsA patients. No differences in GC use or cumulative GC dose were found. All results could be confirmed when groups were matched by age and gender.Conclusion:Our results demonstrate that patients with PsA display higher bone density compared to age and gender matched patients with ankylosing spondylitis. Possible influencing factors could be the higher frequency of csDMARD use, higher BMI or the lower frequency of back pain in PsA patients. Multivariate tests and additional biomarker investigations in larger cohorts are necessary to corroborate these findings and to identify underlying pathogenic differences which could serve for an explanation.Disclosure of Interests:Desiree Freier: None declared, Edgar Wiebe: None declared, Robert Biesen: None declared, Thomas Buttgereit: None declared, Sandra Hermann: None declared, Timo Gaber: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

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