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 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 AB0329 PHYSICIANS’ PRE-LAUNCH AWARENESS AND CONCERNS WITH PIPELINE JANUS KINASE INHIBITORS (JAKIS) VERSUS TOFACITINIB AND BARICITINIB IN RHEUMATOID ARTHRITIS IN THE UNITED STATES AND EUROPE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.1-1463
Author(s):  
D. Baldock ◽  
G. Giannakopoulou
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Patient Characteristics ◽  
The United States ◽  
Janus Kinase ◽  
Personal Awareness ◽  
Medical Chart Review ◽  
The Us ◽  
The Usa ◽  
The Eu

Background:Clinical data regarding use of tofacitinib and baricitinib in rheumatoid arthritis patients have recently posed safety concerns, with regulatory bodies suggesting limiting use of higher dosages. Investigating physicians’ awareness and views of each of these products leading up to their launch, as well as the physicians’ patient characteristics, may provide evidence of how pipeline JAKis could be received in the treatment landscape once approved.Objectives:The objective of the study was to investigate awareness and anticipated concerns of upcoming versus already launched JAKis among a sample of treating rheumatologists in the US and EU5 countries, and assess potential correlation between sampled physicians’ views on JAKis and their managed patient characteristics.Methods:A multi-country, multi-center online medical chart review study of patients with RA was conducted across 2011 – 2019 among rheumatologists in hospitals and private practices to collect de-identified data on a sample of patients who were recently treated with a biologic/JAKi in the USA & EU5 (UK, France, Italy, Spain, Germany). Physicians were screened for duration of practice (3-30 years) and patient volume (≥2 RA biologic/JAKi patients per week) and recruited from a large, geographically representative access panel. Patient charts were recorded for the next 5 eligible patients seen during the screening period. Respondents abstracted patient demographics and personal awareness and concerns for drugs in development. Sites waived local ethics review owing to collection of retrospective de-identified data. Data were analyzed using descriptive statistics.Results:In Q1 19, 56.2% and 56.2% of sampled US physicians were aware of upadacitinib (upa) and filgotinib (filgo), respectively1. Prior to US launch, tofacitinib (tofa) and baricitinib (bari) achieved respective awarenesses of 89.9% (Q4 11, n = 109)2and 85.2% (Q2 17, n= 101)3. Among 262 sampled EU5 rheumatologists, pre-launch awareness in of upa and filgo in Q1 19 was 46.2% and 45.8%1, while for tofa and bari it was 46.2% and 45.8%, respectively (Q2 16, n= 380)4. ‘Poor safety profile’ was cited as a common anticipated concern for upa and filgo, 9.9% of sampled physicians aware of upa (n=121) and 7.5% of those aware of filgo (n=120)1, with the respective scores for tofa and bari prior to their launch being 16.9% (n = 296) and 14.5% (n= 227)4. Sampled patient characteristics in each physician segment (upa concerned n= 449 patients /non-concerned, n= 155 patients; filgo concerned, n= 454 patients /non-concerned, n= 145 patients) included: (a) age in years 54.6/51, p<0.01; 53.9/51.2, p<0.05 (b) retired employment status 31%/20.6%, p<0.05; 29.5%/20%, p<0.051.Conclusion:In this sample, upa and filgo achieved lower awareness scores, compared to tofa and bari prior their launch. Sampled EU5 physicians were less concerned with upa and filgo’s safety profiles, than for the other two JAKis before launch. Sampled physicians holding concerns with upa/filgo manage significantly older patients and a significantly higher number of retired patients. Further investigation using comparator cohort is warranted.References:[1]Ipsos Global Rheumatoid Arthritis Therapy Monitor (Q1 2019, 262 sampled rheumatologists in the EU and 115 sampled rheumatologists in the US reporting on a sample of RA patients seen in their practice; data collected online).[2]Ipsos Global Rheumatoid Arthritis Therapy Monitor (Q4 2011, 109 sampled rheumatologists in the US reporting on a sample of RA patients seen in their practice; data collected online).[3]Ipsos Global Rheumatoid Arthritis Therapy Monitor (Q2 2017, 101 sampled rheumatologists in the US reporting on a sample of RA patients seen in their practice; data collected online).[4]Ipsos Global Rheumatoid Arthritis Therapy Monitor (Q2 2016, 380 sampled rheumatologists in the EU reporting on a sample of RA patients seen in their practice; data collected online).© Ipsos 2020, all rights reservedDisclosure of Interests:None declared

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 Are Janus Kinase Inhibitors Superior over Classic Biologic Agents in RA Patients?

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Przemyslaw J. Kotyla
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune System ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Cell Metabolism ◽  
Theoretical Background ◽  
Janus Kinase ◽  
Biologically Active ◽  
System Functioning ◽  
And Function

The Janus Kinases (JAKs) are a family of intracellular tyrosine kinases that provide transmission signals from cytokine, interferons, and many hormones receptors to the nucleus resulting in synthesis of many biologically active compounds and changing cell metabolism and function. That was theoretical background to synthetize the JAK inhibitors (Jakinibs). In recent years a substantial battery of evidence has been collected indicating the potential role of Jakinibs to interact with the specific elements of the immune system, therefore changing the inflammatory response. JAK kinase blockade offers a unique opportunity to block most of the key cytokines enabling the deep interaction into immune system functioning. Following discovery first Jakinibs were intensively studied in various forms of autoimmune diseases, including rheumatoid arthritis, and finally two Jakinibs tofacitinib and Baricitinib have been approved for the treatment of rheumatoid arthritis. Some clinical data indicated that under special circumstances Jakinibs may be even superior to biologics in the treatment of RA; however this suggestion should be verified in large clinical and observational studies.

scholarly journals Placebo Response in Rheumatoid Arthritis Clinical Trials

2019 ◽  
Vol 47 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Katie Bechman ◽  
Mark Yates ◽  
Sam Norton ◽  
Andrew P. Cope ◽  
James B. Galloway
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Placebo Response ◽  
Janus Kinase ◽  
Controlled Trials ◽  
American College Of Rheumatology ◽  
Factor Therapy ◽  
Expectation Bias ◽  
Over Time

Objective.Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an increasing placebo response makes it harder to detect potential benefit. The objective of this study is to assess the change in placebo responses over time in rheumatoid arthritis (RA) randomized placebo-controlled trials (RCT) for drug licensing authorization.Methods.The Cochrane Controlled Trials Register database was searched to identify RCT of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD) in RA. Studies were excluded if patients were conventional synthetic DMARD (csDMARD)–naive, not receiving background csDMARD therapy, or were biologic experienced. Metaregression model was used to evaluate changes in American College of Rheumatology (ACR) 20, ACR50, and ACR70 treatment response over time.Results.There were 32 trials in total: anti–tumor necrosis factor therapy (n = 15), tocilizumab (n = 4), abatacept (n = 2), rituximab (n = 2), and Janus kinase inhibitors (n = 9). From 1999 to 2018, there was no significant trend in the age or sex of patients in the placebo arm. Disease duration, swollen joint count, and 28-joint count Disease Activity Score using erythrocyte sedimentation rate at baseline all significantly declined over time. There was a statistically significant increase in placebo ACR50 and ACR70 responses (ACR50 β = 0.41, 95% CI 0.09–0.74, p = 0.01; ACR70 β = 0.18, 95% CI 0.04–0.31, p = 0.01) that remained significant after controlling for potential confounders.Conclusion.There has been a rise in the placebo response in RA clinical trials over the last 2 decades. Shifting RA phenotype, changes in trial design, and expectation bias are possible explanations for this phenomenon. This observation has important implications when evaluating newer novel agents against established therapies.

scholarly journals Monitoring the transition of patients on biologics in rheumatoid arthritis: Consensus guidance for pharmacists

2021 ◽  
Vol 19 (3) ◽  
pp. 2377
Author(s):  
Denis Choquette ◽  
Jonathan Chan ◽  
Mohammad Bardi ◽  
Carolyn Whiskin ◽  
Gabriel Torani ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Best Practices ◽  
Kinase Inhibitors ◽  
Unmet Need ◽  
Nominal Group Technique ◽  
Janus Kinase ◽  
Nominal Group ◽  
Nocebo Effect ◽  
Patient Journey ◽  
Janus Kinase Inhibitors

Background: Recent approvals for novel agents such as the small molecule Janus kinase inhibitors (JAKi), combined with the advent of biosimilars has widened the gamut of available therapeutic options in the treatment of rheumatoid arthritis (RA). This combined with the introduction of mandatory non- medical switches to biosimilars in some jurisdictions by both public and private payors has led to a significant increase in the volume of therapeutic changes for patients. Pharmacists are well positioned to ensure effective and safe transitions, however there is a significant unmet need for objective and subjective clinical guidance around therapy as well disease state monitoring in RA that facilitates best practices throughout the patient journey. Objective: In this paper we aim to create a consensus derived monitoring algorithm for pharmacists to facilitate best practices throughout therapeutic transitions from originator biologic to other originator biologics, biosimilars, and Janus kinase inhibitors in RA. Methods: The Nominal Group Technique (NGT) was used to understand if consensus could be found among the participants. Clinically relevant questions were developed to capture solutions to the identified unmet need. The faculty considered the questions as individuals, and privately generated answers/ideas. After discussion and consideration, the participants ranked the ideas and established a consensus. Results: Based on the outcome of the consensus discussions, an algorithm was created to help guide pharmacists through therapeutic transitions in RA. The tool covers important topics such as pre-transition considerations, avoiding the nocebo effect for biosimilars, specific considerations for each drug or class, monitoring efficacy, and when to refer. Conclusions: New classes of anti-rheumatic drugs including JAKi, along with the introduction of biosimilars are presenting more opportunity for therapeutic changes and monitoring in patients with RA. We hope our evidence-based consensus derived guidance tool will assist frontline pharmacists in supporting their patients to a successful therapeutic transition in RA.

Sign in / Sign up

Export Citation Format

Share Document