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Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study.Frontiers in Immunology 2023The ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those...
BACKGROUND
The ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.
METHODS
We retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.
RESULTS
After PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67-7.42) for malignancy and 3.03 (95% CI: 0.77-15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23-2.97).
CONCLUSION
The IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Interleukin-6 Inhibitors; Janus Kinase Inhibitors; Neoplasms; Retrospective Studies
PubMed: 37868999
DOI: 10.3389/fimmu.2023.1267749 -
International Journal of Nanomedicine 2023Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At... (Review)
Review
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA.
Topics: Humans; Administration, Cutaneous; Skin; Arthritis, Rheumatoid; Antirheumatic Agents; Inflammation; Drug Delivery Systems
PubMed: 38144510
DOI: 10.2147/IJN.S435251 -
RMD Open Mar 2023
Topics: Humans; Pregnancy; Female; Methotrexate; Antirheumatic Agents; Arthritis, Rheumatoid
PubMed: 36921981
DOI: 10.1136/rmdopen-2022-002899 -
Endocrine Regulations Apr 2022Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The...
Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Factors; Disease Progression; Humans; Prognosis
PubMed: 35489053
DOI: 10.2478/enr-2022-0016 -
Rheumatology (Oxford, England) Aug 2022Management of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining... (Review)
Review
Management of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining symptomatic after failing biological and/or targeted synthetic DMARDs. Multiple factors can contribute to D2T RA, including treatment non-adherence, comorbidities and co-existing mimicking diseases (e.g. fibromyalgia). Additionally, currently available biological and/or targeted synthetic DMARDs may be truly ineffective ('true' refractory RA) and/or lead to unacceptable side effects. In this narrative review based on a systematic literature search, an overview of underlying (immune) mechanisms is presented. Potential scenarios are discussed including the influence of different levels of gene expression and clinical characteristics. Although the exact underlying mechanisms remain largely unknown, the heterogeneity between individual patients supports the assumption that D2T RA is a syndrome involving different pathogenic mechanisms.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Comorbidity; Humans
PubMed: 35238332
DOI: 10.1093/rheumatology/keac114 -
Current Opinion in Rheumatology Sep 2021Given the role of inflammation in severe forms of COVID-19, glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) have been assessed as potential COVID-19... (Review)
Review
PURPOSE OF REVIEW
Given the role of inflammation in severe forms of COVID-19, glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) have been assessed as potential COVID-19 therapies.
RECENT FINDINGS
Randomized controlled trials (RCTs) have shown that glucocorticoids reduce mortality in severe COVID-19. RCTs of DMARDs have shown mixed results varying on intervention and inclusion criteria. DMARDs, including colchicine or biologic agents, may improve COVID-19 outcomes in specific patient populations.
SUMMARY
Glucocorticoids are an effective treatment for the management of severe COVID-19. Further studies are needed to better define the patient populations who could benefit from DMARD use, as well as provide guidance regarding the timing of these interventions.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Factors; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34397605
DOI: 10.1097/BOR.0000000000000817 -
European Review For Medical and... Feb 2020Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents,... (Review)
Review
OBJECTIVE
Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents, it is still difficult to identify the most effective and safest available treatment. The choice and comparison between biological agents are a challenge, for only limited head-to-head clinical studies are available. The aim of this manuscript is to review the published network meta-analysis (NMA) to gain a better understanding of efficacy and safety of biological agents and small molecules in the management of RA patients.
MATERIALS AND METHODS
We used MEDLINE and EMBASE to identify network meta-analyses from 2008 to June 2019 comparing efficacy and safety of licensed biological agents and tsDMARDS at the approved dosages using predefined text words related to the topic. The following scenarios have been investigated: patients not responding to csDMARD (cDMARDs - IR); csDMARD naïve patients; patients not responding to biologics (bDMARDs - IR); patients in biological monotherapy.
RESULTS
On the basis of the data present in the literature, we are able to hypothesize some trends of response in terms of efficacy in different subsets of patients, for example patients in monotherapy, bDMARds unresponsive patients, and Methotrexate-naive patients. The differences of the results presented in many works are due to the different inclusion criteria used in the studies, the type of biologics agent used in each study (according to the available molecules in the different years of publication), as well as differences in the methodology of NMA and in the presentation of the data.
CONCLUSIONS
We suggest that the next NMA follows the indications suggested by the Professional Society for Health Economics and Outcomes Research (ISPOR) so that the results are comparable and comprehensible.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Humans; Network Meta-Analysis
PubMed: 32141529
DOI: 10.26355/eurrev_202002_20337 -
Eye (London, England) Jun 2021
Topics: Antirheumatic Agents; Humans; Hydroxychloroquine; Ophthalmologists; Prevalence; Retinal Diseases; United Kingdom
PubMed: 33514907
DOI: 10.1038/s41433-021-01411-6 -
Clinical and Experimental Rheumatology Nov 2023New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying... (Review)
Review
New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.
Topics: Female; Pregnancy; Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Vaccination
PubMed: 37497719
DOI: 10.55563/clinexprheumatol/nat8nl -
Clinical Immunology (Orlando, Fla.) Sep 2020Over the past few years, there have been several scientific advances related to the discovery of interleukin 23 (IL-23) and IL-17 which led to the development of new...
Over the past few years, there have been several scientific advances related to the discovery of interleukin 23 (IL-23) and IL-17 which led to the development of new treatment options and overall improved clinical care of Psoriatic Arthritis (PsA) patients. Many of these efforts and milestones, alongside new developments, are captured in this Clinical Immunology special edition. We also take the opportunity to highlight the overall scientific progress in PsA research and also highlight some areas of concern that continue to represent barriers in the PsA arena that need to be addressed. These areas are 1) basic & translational research, 2) clinical diagnosis 3) treatment and 4) medical education and awareness.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biomedical Research; Education, Medical; Humans
PubMed: 32621978
DOI: 10.1016/j.clim.2020.108519