scholarly journals JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1002 ◽  
Author(s):  
Jacopo Angelini ◽  
Rossella Talotta ◽  
Rossana Roncato ◽  
Giulia Fornasier ◽  
Giorgia Barbiero ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Real Life ◽  
Rapid Onset ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Biological Drugs ◽  
Disease Modifying Drugs

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.

Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis

2021 ◽  
Author(s):  
Kosuke Ebina
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Elderly Patients ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Treatment Recommendation ◽  
Efficacy And Safety ◽  
Old Patients ◽  
Janus Kinase Inhibitors ◽  
Increased Risk

ABSTRACT Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.

scholarly journals Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Caterina Vacchi ◽  
Andreina Manfredi ◽  
Giulia Cassone ◽  
Stefania Cerri ◽  
Giovanni Della Casa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Kinase Inhibitors ◽  
Therapeutic Option ◽  
Real Life ◽  
Janus Kinase ◽  
Joint Involvement ◽  
Infectious Risk ◽  
Systemic Inflammatory Disease

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.

scholarly journals Rheumatoid arthritis and myasthenia gravis: a case-based review of the therapeutic options

2022 ◽  
Author(s):  
Riccardo Bixio ◽  
Davide Bertelle ◽  
Francesca Pistillo ◽  
Elisa Pedrollo ◽  
Antonio Carletto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Myasthenia Gravis ◽  
Tumor Necrosis ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Janus Kinase ◽  
Therapeutic Options ◽  
Tumor Necrosis Factor Inhibitors ◽  
Necrosis Factor

Abstract Introduction Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients with rheumatoid arthritis present an increased prevalence of myasthenia gravis compared to the general population. While these two diseases share some therapeutic options, such as glucocorticoids, methotrexate, and rituximab, there are no guidelines for treating concomitant disease. We aim to review the available evidence and to discuss the efficacy and safety of the therapeutic options in patients with rheumatoid arthritis associated with myasthenia gravis. Method We described three patients with rheumatoid arthritis associated with myasthenia gravis and we performed a systematic review of the associated literature. Results A 48-year-old man and two women (48 and 55 years old) with concomitant diagnoses of active rheumatoid arthritis and well-controlled myasthenia gravis are described. They were treated with methotrexate, leflunomide, upadacitinib, and adalimumab. None of them experienced changes in their myasthenic symptoms. We found 9 additional cases from our literature review. Methotrexate, rituximab, upadacitinib, diphenyl sulfone, auranofin, and loxoprofen sodium did not show an impact on the seven patients with previously well-controlled myasthenia. Glucocorticoids, methotrexate, and rituximab proved effective in active myasthenia gravis and arthritis. Conflicting data emerged for Tumor-necrosis factor inhibitors. Conclusions Although the available evidence remains scarce, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options. The role of tumor-necrosis factor inhibitors remains uncertain. Eventually, Janus Kinase inhibitors are a novel interesting option for these patients. Key Points• To date, the only evidence on the treatment of patients with rheumatoid arthritis and concomitant myasthenia gravis derives from case reports.• Based on the review of the available case reports and on the cases we described, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options, while the role of Tumor-necrosis factor inhibitors remains uncertain.• Based on the cases we described, Janus Kinase inhibitors are a novel interesting option for patients with concomitant rheumatoid arthritis and myasthenia gravis.

scholarly journals Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

2021 ◽  
Author(s):  
Pedro Jesús Gómez-Arias ◽  
Francisco Gómez-García ◽  
Jorge Hernández-Parada ◽  
Ana María Montilla-López ◽  
Juan Ruano ◽  
...  
Keyword(s):  
Scoping Review ◽  
Kinase Inhibitors ◽  
Type I Interferon ◽  
Janus Kinase ◽  
Type I ◽  
Efficacy And Safety ◽  
Autoinflammatory Disorders ◽  
Janus Kinase Inhibitors

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.

Switching from Intravenous to Subcutaneous Formulation of Abatacept: A Single-center Italian Experience on Efficacy and Safety

2014 ◽  
Vol 42 (2) ◽  
pp. 193-195 ◽  
Author(s):  
Rossella Reggia ◽  
Franco Franceschini ◽  
Angela Tincani ◽  
Ilaria Cavazzana
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Activity ◽  
Disease Control ◽  
Safety Profile ◽  
Efficacy And Safety ◽  
Single Center ◽  
Italian Experience ◽  
Laboratory Features ◽  
Risk Of Relapse

Objective.Subcutaneous (SC) abatacept (ABA) is comparable to intravenous (IV) formulation in terms of efficacy and safety profile. Our work analyzed the switch to SC formulation from IV administration in patients with rheumatoid arthritis.Methods.Fifty-one patients treated with SC ABA were included. Clinical data were obtained from clinical charts.Results.Fourteen patients relapsed and needed to return to the IV administration. Neither clinical and laboratory features nor the previous therapies were identified as risk factors for SC formulation inefficacy. Disease activity decreased after the return to IV infusions.Conclusion.SC ABA showed a risk of relapse in 27% of cases. The reinsertion of the IV administration quickly reinstated disease control.

scholarly journals Oral Janus Kinase Inhibitor for the Treatment of Rheumatoid Arthritis: Tofacitinib

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Han Ni ◽  
Soe Moe ◽  
Kay Thi Myint ◽  
Aung Htet
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Serious Adverse Events ◽  
Janus Kinase Inhibitor ◽  
Immune Modulators ◽  
Serious Infections

Since the introduction of immune modulators in the treatment of rheumatoid arthritis (RA), there has been hope that orally effective biologic agents would be developed. Tofacitinib, a Janus kinase inhibitor, has become the first oral biologic to receive approval for use in active RA patients. This paper reviews the efficacy and safety profile of Tofacitinib at dosages of 5 mg and 10 mg twice daily. Remarkable improvement in terms of ACR 20 response and HAQ-DI score was noted at month 3 and month 6. DAS 28-4 ESR < 2.6 achievement was noticeably obvious at month 6 for both dosages. No significant serious adverse events, serious infections, neutropenia, or anaemia were observed compared to placebo. In fact, Tofacitinib 5 mg was even found to have significant protective effect of anaemia in the meta-analysis (P=0.004). Tofacitinib has a noticeable efficacy in controlling disease activity in RA with a manageable safety profile. However, longer studies are needed for its long-term safety profile.

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