scholarly journals AB0269 ARE INTERFERON-GAMMA RELEASE ASSAYS RELIABLE TO DETECT TUBERCULOSIS INFECTION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH JANUS KINASE INHIBITORS?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1160.3-1161
Author(s):  
C. Castellani ◽  
E. Molteni ◽  
A. Altobelli ◽  
C. Garufi ◽  
S. Mancuso ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chest Radiography ◽  
Kinase Inhibitors ◽  
Clinical Manifestations ◽  
Latent Tuberculosis ◽  
Median Number ◽  
Janus Kinase ◽  
Tuberculosis Infection ◽  
Jak Inhibitors ◽  
Perfect Agreement

Background:The therapeutic armamentarium for patients with rheumatoid arthritis (RA) has recently been enriched with the family of Janus kinase (JAK) inhibitors. Because the risk of reactivation of latent tuberculosis infection (LTBI) following the use of these drugs seems to be similar to that seen with anti-TNF agents, screening for LTBI is recommended in patients with RA before starting treatment with JAK inhibitors. Interferon(IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. However, JAK inhibitors tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with this novel class of drugs.Objectives:To compare the performance of the QuantiFERON-TB Gold Plus (QFT-Plus) test with that of QuantiFERON-TB Gold In-tube (QFT-GIT) assay in RA patients before and during treatment with JAK inhibitors.Methods:A longitudinal, prospective study has been performed in RA patients (ACR/EULAR 2010 criteria) candidates for tofacitinib or baricitinib treatment. All patients underwent QFT-Plus and QFT-GIT at baseline (T0), and after 3 (T3) and 9/12 months (T9/12) of treatment with JAK inhibitors. The agreement of the two tests was calculated at all timepoints. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. Lastly, the variability of QTF-Plus results was assessed during follow-up.Results:Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled: among them, 22 were to start baricitinib (75.9%) and 7 tofacitinib (24.1%). A perfect agreement was found between QFT-Plus and QFT-GIT at all times of observation (κ=1). At baseline, no agreement was recorded between IGRAs and TST (κ=-0.08) and between TST and chest radiography (κ=-0.07), while a low agreement was found between QFT-Plus and chest radiography (κ=0.17). A variation of 33.3% in the results of the QFT-Plus test was recorded at T3 compared to T0, of 29.4% at T9/12 compared to T0, and of 11.8% at T9/12 compared to T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-Plus decreased after 3 months of treatment (1.59/4.72 IU/ml vs 3.08/7.68 IU/ml at baseline), followed by an increase after 9/12 months (2.25/4.61 IU/ml), but these differences were not significant. No significant change in the median number of circulating lymphocytes such as to explain the variation of the QFT-Plus results after 3 months of JAK inhibitor therapy was documented (1815/690/mm3 vs 2140/750/mm3 at baseline). At baseline, both QFT-Plus and QFT-GIT showed positive results in 5 patients (17.2%), negative in 19 (65.5%), and indeterminate in 5 (17.2%). Glucocorticoids intake was associated with a higher probability of negative or indeterminate result of IGRAs at baseline (p<0.0001).Conclusion:Our data show that a response to IGRAs is detectable in the course of treatment with JAK inhibitors. However, similarly to what has been observed during treatment with TNF antagonists, the results of QFT-GIT and QFT-Plus show some variability when longitudinally repeated. These fluctuations occur in the absence of correlation with clinical outcome, thus challenging their interpretation. Since we do not have a sufficiently sensitive test capable of detecting TB infection, an integrated evaluation of risk factors, clinical manifestations and multiple diagnostic tests should be considered for a proper evaluation of the risk of TB infection in immunosuppressed patients.Disclosure of Interests:None declared

scholarly journals Janus kinase inhibitors for the treatment of rheumatoid arthritis

2021 ◽  
Vol 64 (2) ◽  
pp. 105-108
Author(s):  
Sun Hee Jang ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Interleukin 1 ◽  
Janus Kinase ◽  
Jak Inhibitor ◽  
Jak Inhibitors ◽  
Biologic Dmards ◽  
Signal Transducers ◽  
Refractory Rheumatoid Arthritis ◽  
Stat Signaling

Rheumatoid arthritis is a chronic inflammatory destructive disorder that affects the joints, muscles, and tendons accompanying various extra-articular manifestations. Traditional disease-modifying anti-rheumatic drugs (DMARDs) represent the basic treatment for rheumatoid arthritis. Over the last 20 years, biologic DMARDs (tumor necrosis factor inhibitors, interleukin-1 inhibitors, interleukin-6 inhibitors, T cell inhibitors, and B cell inhibitors) have been widely used as a novel class of DMARDs that have efficacy and efficiency. Discovery of the underlying pathogenesis of autoimmune disease enables us to develop new target therapies such as a Janus kinase (JAK) inhibitor. Activated JAK is known to activate signal transducers as well as activators of transcription (STAT) signaling. A JAK inhibitor is a type of medication that functions by inhibiting the JAK-STAT signaling pathway. In addition, it is easy to take a JAK inhibitor orally. In Korea, several JAK inhibitors have been approved. This review describes the types of JAK inhibitors, recommended doses, side effects, and updated European Alliance of Associations for Rheumatology guidelines. Clinicians should more often consider JAK inhibitors in the treatment of refractory rheumatoid arthritis in current rheumatology clinics

scholarly journals Clinical significance of Janus kinase inhibitors in the therapy of rheumatoid arthritis: achievements and prospects

2019 ◽  
Vol 13 (4) ◽  
pp. 116-123 ◽  
Author(s):  
V. I. Mazurov ◽  
I. B. Belyaeva
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Weight ◽  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Expected Effect ◽  
Signaling Systems ◽  
Disease Modifying

Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight <1 kDa for oral administration) that inhibit the activity of intracellular signaling systems. The authors consider the clinical achievements and prospects, which open the use of JAK inhibitors in the treatment of RA.

scholarly journals O27 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Lianne Kearsley-Fleet ◽  
Rebecca Davies ◽  
Kath Watson ◽  
Mark Lunt ◽  
Kimme L Hyrich ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Patient Characteristics ◽  
Median Number ◽  
Outcome Data ◽  
Janus Kinase ◽  
Oral Disease ◽  
British Society ◽  
Biologic Dmards ◽  
The Uk

Abstract Background In 2017, a new class of oral disease modifying anti-rheumatic drugs (DMARDs), janus kinase inhibitors (JAKi), were licensed for rheumatoid arthritis (RA): baricitinib and tofacitinib. In the UK, they are approved for use in patients with high disease activity with or without methotrexate, following failure of conventional synthetic (cs) DMARDs or biologic DMARDs, the latter when rituximab is contraindicated. As a new therapy option, it is currently unclear how and when these drugs are being prescribed in patients with RA. This analysis aims to describe the characteristics of patients starting JAKi and registered with the BSRBR-RA. Methods The BSRBR-RA aims to capture exposure and outcome data in patients with RA receiving biologics, biosimilars and targeted synthetic DMARDs. At the start of therapy, demographic and clinical data, including past treatment data, are collected. Characteristics of all patients receiving a JAKi for the first time with data recorded in the BSRBR-RA up to 31/03/2019 are described. Results To 31/03/2019, 698 patients in the BSRBR-RA have been treated with a JAKi; 596 patients baricitinib and 110 tofacitinib (Table 1). A quarter of patients received a JAKi with no prior biologic exposure; 148 (25%) baricitinib and 16 (15%) tofacitinib. Of these, 15% had a prior malignancy history. Of those with prior biologic exposure, the median number of previous biologics was 3 (IQR 2-4), the majority had prior TNFi (91%) or rituximab (51%), and 50% were receiving concurrent methotrexate. Conclusion To date, more patients have been recruited starting baricitinib than tofacitinib, likely owing to the later licensing of tofacitinib. Two groups are emerging with a quarter of patients receiving JAKi immediately after csDMARDs and a majority as a later stage alternative following multiple biologics. Further recruitment and follow-up patients will allow for analysis of real-world safety and effectiveness, but differences in patient characteristics will need to be considered in any comparative effectiveness analyses. Disclosures L. Kearsley-Fleet None. R. Davies None. K. Watson None. M. Lunt None. K.L. Hyrich Honoraria; AbbVie. Grants/research support; UCB, Pfizer, BMS.

scholarly journals Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

2017 ◽  
Vol 52 (10) ◽  
pp. 667-668 ◽  
Author(s):  
Senir Turan ◽  
Scot Walker
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Reactions ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Oral Drugs ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Skin Conditions

Rheumatoid arthritis (RA) is a disease where the immune system attacks the linings of the joints, resulting in joint pain, stiffness, swelling, and destruction. Although many products are available for the treatment of RA, limitations such as adverse reactions and tolerance greatly affect adherence. Many of the current biologic disease-modifying antirheumatic drugs on the market are injectables, leaving a void to be filled for a product that can be taken orally. The most advanced of these approaches, the Janus kinase (JAK) inhibitors, are oral drugs that have not only made a breakthrough in RA, but also other skin conditions.

scholarly journals Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews

2022 ◽  
Vol 12 ◽  
Author(s):  
Yun-Kyoung Song ◽  
Junu Song ◽  
Kyungim Kim ◽  
Jin-Won Kwon
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Proportional Reporting Ratio ◽  
Gastrointestinal Disorder ◽  
Interstitial Lung Diseases ◽  
Janus Kinase ◽  
Reporting Odds Ratio ◽  
Jak Inhibitors ◽  
Spontaneous Reports

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

scholarly journals Comparison of Quantiferon-TB Gold and TST tests in the diagnosis of latent tuberculosis infection among HIV infected patients in Hamadan, west of Iran

2020 ◽  
Vol 14 (04) ◽  
pp. 360-365
Author(s):  
Fariba Keramat ◽  
Benyamin Bagheri Delavar ◽  
Alireza Zamani ◽  
Jalal Poorolajal ◽  
Elham Lajevardi ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Latent Tuberculosis Infection ◽  
Demographic Data ◽  
Clinical Manifestations ◽  
Latent Tuberculosis ◽  
Cd4 Count ◽  
Tuberculosis Infection ◽  
Percent Agreement ◽  
Immunodeficiency Virus ◽  
The Mean

Introduction: Human immunodeficiency virus (HIV) infection increases the susceptibility of patients for latent tuberculosis infection (LTBI) and reactivtion tuberculosis. This study aimed to compare the Quantiferon-TB gold-in tube test (QFT) with tuberculin skin test (TST) in the diagnosis of LTBI in HIV infected patients. Methodology: This comparative study of 89 patients with HIV in the Behavioral Diseases Counseling Center in Hamadan was carried out from July 2015 to November 2016. After obtaining consent from the patients, all demographic data, clinical manifestations, and laboratory results (CD4 count, TST and QFT) were entered into the questionnaires. The CD4 count is usually routinely performed using flow cytometry at the Behavioral Counselling Center. Quantiferon-TB test was done by using Qiagen – Quantiferon-2 plate kit ELISA. Results: Totally, 89 HIV infected patients with the mean age of 39.55 ± 10.31 years old were enrolled in the study. Sixty patients (67.42%) were male. The mean duration of HIV infection was 4.44 ± 3.88 years and the mean of CD4 count was 388.65 ± 260.66 cells/µL . Twenty patients had LTBI based on TST. Considering the QFT intermediate results as a positive test, the percent agreement of QFT and TST was 59.55%, which was not statistically significant (P = 0.2387). Conclusions: According to the results, there was no significant percent agreement between QFT and TST for detecting LTBI in HIV infected patients. However, by decreasing CD4 counts, there was a significant relation between TST positive and LTBI in HIV patients.

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