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 POS0088 EFFICACY OF JANUS KINASE INHIBITORS FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 252-253
Author(s):  
M. Kamiya ◽  
D. Togawa ◽  
S. Mori ◽  
K. Yamazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Retention Rate ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Necrosis Factor ◽  
Drug Retention Rate

Background:In 20-30% of rheumatoid arthritis (RA) patients, the first biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)) is ineffective, and among the patients who do respond to therapy, 20% is faced with secondary ineffectiveness within the first 2 years of treatment [1]. In practice, when refractory RA is present, of which the definition implies previous use of at least two bDMARDs (generally TNFis), the next treatment choice often made is a bDMARD of another class (non-TNFis) [2]. On the other hand, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARD treatment reduces their response [3]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis.Objectives:Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(4). We evaluated real world efficacy of approved JAKis and factors that may help to continue them in patients with D2T RA.Methods:Patients who had inadequate response to two or more bDMARDs (including both TNFis and non-TNFis) at our hospital by December 2019 were defined as D2T RA, and patients who switched to JAKis were retrospectively investigated. The drug retention rate was determined by Kaplan-Meier method, and the difference was tested by Logrank test. Multiple regression analysis was used as the statistical method to predict continuation of JAKis for more than 1 year, with patient background (age, gender, during the disease, number of bDMARDs used, with or without methotrexate and/or glucocorticoids, disease activity score assessing 28 joints using erythrocyte sedimentation rate’ presence of rheumatoid factor/anti-CCP antibody, matrix metalloproteinase 3 value, Health Assessment Questionnaire disability index) at the time of initiation as an explanatory variable.Results:A total of 915 bDMARDs had been administered to 394 RA patients. The retention rate of bDMARDs and the number of bDMARDs used were 89.3% and 1.48 bDMARDs at 1 year, 67.7% and 2.27 bDMARDs at 5 years, and 52.0% and 3.15 bDMARDs at 10 years, respectively. The retention rate of JAKis at 1 year was 60.2% in 65 patients with tofacitinib (TOF) and 67.2% in 70 patients with baricitinib (BAR) (P=0.38). Among them, the drug retention rate in D2T RA patients was 50.8% in 38 TOF patients and 66.3% in 35 BAR patients with no significant difference (P=0.30). There were no patient background factors that significantly predicted continuation at 1 year for any JAKis.Conclusion:Despite the limited number of patients and the retrospective nature of the study, TOF and BAR were shown to be effective options for D2T RA, regardless of patient background such as disease activity or number of bDMARDs used. Other JAKis and switches between JAKis need to be investigated in the future.References:[1]Schaeverbeke T, Truchetet ME, Kostine M et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016;55:210_20.[2]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[3]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[4]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

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 Conventional Disease-Modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 1 (5) ◽  
Author(s):  
Shannon Hill ◽  
Nina Frey
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Modifying ◽  
Evidence Based Guidelines

Nine evidence-based guidelines were identified that recommend the use of conventional synthetic disease-modifying antirheumatic drugs as a first-line therapy for patients with rheumatoid arthritis prior to using biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors. Methotrexate monotherapy was the most commonly recommended conventional synthetic disease-modifying antirheumatic drug recommended as first-line therapy by the included guidelines. Eight of the included guidelines recommend combination therapy using multiple conventional synthetic disease-modifying antirheumatic drugs if monotherapy is ineffective and 4 included guidelines recommend the use of glucocorticoids in combination with conventional synthetic disease-modifying antirheumatic drugs.

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 Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology – what we know and what we do not know from randomized controlled trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tatjana Welzel ◽  
Carolyn Winskill ◽  
Nancy Zhang ◽  
Andreas Woerner ◽  
Marc Pfister
Keyword(s):  
Certolizumab Pegol ◽  
Paediatric Rheumatology ◽  
Janus Kinase ◽  
Pharmacokinetic Data ◽  
Disease Course ◽  
Jak Inhibitors ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Age Dependent ◽  
Disease Modifying

Abstract Background Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent changes, disease course, and pharmacokinetic processes paediatric patients with inflammatory rheumatic diseases (PiRD) differ from adult rheumatology patients. Methods A systematic literature search for randomized clinical trials (RCTs) in PiRD treated with bDMARDs/JAK inhibitors was conducted on Medline, clinicaltrials.gov, clinicaltrialsregister.eu and conference abstracts as of July 2020. RCTs were included if (i) patients were aged ≤20 years, (ii) patients had a predefined rheumatic diagnosis and (iii) RCT reported predefined outcomes. Selected studies were excluded in case of (i) observational or single arm study or (ii) sample size ≤5 patients. Study characteristics were extracted. Results Out of 608 screened references, 65 references were selected, reporting 35 unique RCTs. All 35 RCTs reported efficacy while 34/3 provided safety outcomes and 16/35 provided pharmacokinetic data. The most common investigated treatments were TNF inhibitors (60%), IL-1 inhibitors (17%) and IL-6 inhibitors (9%). No RCTs with published results were identified for baricitinib, brodalumab, certolizumab pegol, guselkumab, risankizumab, rituximab, sarilumab, secukinumab, tildrakizumab, or upadacitinib. In patients with juvenile idiopathic arthritis (JIA) 25/35 RCTs were conducted. The remaining 10 RCTs were performed in non-JIA patients including plaque psoriasis, Kawasaki Disease, systemic lupus erythematosus and non-infectious uveitis. In JIA-RCTs, the control arm was mainly placebo and the concomitant treatments were either methotrexate, non-steroidal anti-inflammatory drugs (NSAID) or corticosteroids. Non-JIA patients mostly received NSAID. There are ongoing trials investigating abatacept, adalimumab, baricitinib, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, risankizumab, secukinumab, tofacitinib and tildrakizumab. Conclusion Despite the FDA Modernization Act and support of major paediatric rheumatology networks, such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), which resulted in drug approval for PiRD indications, there are limited RCTs in PiRD patients. As therapy response is influenced by age-dependent changes, pharmacokinetic processes and disease course it is important to consider developmental changes in bDMARDs/JAK inhibitor use in PiRD patients. As such it is critical to collaborate and conduct international RCTs to appropriately investigate and characterize efficacy, safety and pharmacokinetics of bDMARDs/JAK inhibitors in paediatric rheumatology.

Rheumatoid Arthritis: Strategies for Pharmacotherapy

1999 ◽  
Vol 12 (4) ◽  
pp. 271-281
Author(s):  
Bruce C. Carlstedt ◽  
Walter F. Stanaszek
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Adverse Reactions ◽  
Initial Therapy ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Historically, treatment of rheumatoid arthritis (RA) has been conservative and symptom or patient-complaint oriented. Newer approaches use disease-modifying antirheumatic drugs (DMARDs), sometimes known as slow-acting antirheumatic drugs (SAARDs), to slow the progression of the disease earlier in its course. Some of these drugs may be used as initial therapy and some may be used in combinations to reduce the side effects or adverse reactions.

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