-
The Journal of Rheumatology Aug 2023Rheumatoid arthritis (RA) is a systemic musculoskeletal disease where immune dysregulation and subsequent autoimmunity induce significant synovial joint inflammation and... (Review)
Review
Rheumatoid arthritis (RA) is a systemic musculoskeletal disease where immune dysregulation and subsequent autoimmunity induce significant synovial joint inflammation and damage, causing pain and disability. RA disease onset is promoted through multifaceted interactions between genetic and environmental risk factors. However, the mechanisms of disease onset are not completely understood and disease-specific treatments are yet to be developed. Current RA treatments include nonspecific disease-modifying antirheumatic drugs (DMARDs) that suppress destructive immune responses and prevent damage. However, DMARDs are not curative, and relapses are common, necessitating lifelong therapy in most patients. Additionally, DMARD-induced systemic immunosuppression increases the risk of serious infections and malignancies. Herein, we review the current understanding of RA disease pathogenesis, with a focus on T and B cell immune tolerance breakdown, and discuss the development of antigen-specific RA therapeutics that aim to restore a state of immune tolerance, with the potential for disease prevention and reduction of treatment-associated adverse effects.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Inflammation; Autoimmunity; Immune Tolerance
PubMed: 36725060
DOI: 10.3899/jrheum.220881 -
Autoimmunity Reviews Jan 2024Janus Kinase inhibitors (JAKi) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with... (Review)
Review
Janus Kinase inhibitors (JAKi) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with efficacy similar to, if not greater than, biologic agents. Recently, concerns over their safety was raised by the results from Oral Surveillance trial suggesting that tofacitinib, one of the JAKi, was associated with higher cardiovascular adverse events and malignancies than TNF inhibitors (TNFi). Since then, regulatory authorities have added warnings to the labels of JAKi. On this purpose, whether rheumatologists should use JAKi as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of biosimilar drugs, they are the most cost-effective treatment. On the other hand, JAKi are very efficacious and are generally safe apart from older and high-risk patients. When TNFi are contraindicated and in certain RA patients ,especially when an oral drug is preferable, JAKi have significant advantage providing patients are involved in the decision-making process.
Topics: Humans; Janus Kinase Inhibitors; Antirheumatic Agents; Biological Products; Arthritis, Rheumatoid; Treatment Outcome
PubMed: 37634678
DOI: 10.1016/j.autrev.2023.103429 -
International Immunopharmacology Sep 2023In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the... (Review)
Review
In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the persistent symptoms or signs experienced by patients. The therapeutic demands of patients with D2T RA are not properly met due to unclear pathogenic causes and a lack of high-quality data for current treatment options, creating considerable management difficulties with this patient population. This review describes the clinical challenges associated with disease-modifying antirheumatic drugs (DMARDs) and explores contributing factors associated with inappropriate response to DMARDs that may lead to D2T RA and related immunological dysregulation. It is now understood that D2T RA is a highly heterogeneous pathological status that involves multiple factors. These factors include but are not limited to genetics, environment, immunogenicity, comorbidities, adverse drug reactions, inappropriate drug application, poor adherence, and socioeconomic status. Besides, these factors may manifest in the selection and utilization of specific DMARDs, either individually or in combination, thereby contributing to inadequate treatment response. Finding these variables may offer hints for enhancing DMARD therapy plans and bettering the condition of D2T RA patients.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products
PubMed: 37481847
DOI: 10.1016/j.intimp.2023.110655 -
International Journal of Rheumatic... Nov 2023
Topics: Humans; Arthritis, Juvenile; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic
PubMed: 37563978
DOI: 10.1111/1756-185X.14845 -
Rheumatology (Oxford, England) May 2024
Topics: Humans; Communication; Antirheumatic Agents; Patient Education as Topic; Physician-Patient Relations; Rheumatic Diseases
PubMed: 38145488
DOI: 10.1093/rheumatology/kead706 -
Nature Reviews. Rheumatology Nov 2023Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and...
Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA.
Topics: Humans; Antirheumatic Agents; Axial Spondyloarthritis; Biological Products; Rheumatology; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 37803079
DOI: 10.1038/s41584-023-01034-z -
International Journal of Rheumatic... May 2024
Topics: Humans; Methotrexate; Japan; Antirheumatic Agents; Drug Dosage Calculations; Treatment Outcome; Arthritis, Rheumatoid
PubMed: 38720411
DOI: 10.1111/1756-185X.15176 -
Seminars in Arthritis and Rheumatism Oct 2023To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with... (Review)
Review
OBJECTIVE
To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA) through a systematic review.
METHODS
We searched Medline for journal articles (2001-2021) and Embase® for abstracts presented at the European Alliance of Associations for Rheumatology and American College of Rheumatology (ACR) 2020 and 2021 annual meetings on non-randomized studies comparing the effectiveness of b/tsDMARDs using ACR-recommended disease activity measures, measures of functional status, and patient-reported outcomes (HAQ, PROMIS PF, patient pain, Patient and Physician Global Assessment of disease activity). Methodological heterogeneity between studies precluded meta-analyses. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions-I tool.
RESULTS
Of 1283 records screened, 68 were selected for data extraction, of which 1 was excluded due to critical risk of bias. Most studies were multicenter observational cohort/registry studies (n = 60) and were published between 2011 and 2021 (n = 60). Mean or median reported RA duration was between 6 and 15 years. Disease Activity Score in 28 joints (46 studies), Clinical Disease Activity Index (37 studies), and Health Assessment Questionnaire-Disability Index (32 studies) were the most common outcomes used in clinical practice, with regional differences identified. The most common comparison was between tumor necrosis factor inhibitors (TNFis) and non-TNFi bDMARDs (35 studies). There were no evident differences between b/tsDMARDs in clinical effectiveness.
CONCLUSION
This systematic review summarizing real-world evidence from a very large number of global studies found there are many effective options for the treatment of RA, but relatively less evidence to support the use of any one b/tsDMARD or drug class over another. Treatment for patients with RA should be tailored to suit individual clinical profiles. Further research is needed to identify whether specific patient subgroups may benefit from specific drug classes.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Treatment Outcome; Biological Products; Multicenter Studies as Topic
PubMed: 37573754
DOI: 10.1016/j.semarthrit.2023.152249 -
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 -
Nature Reviews. Rheumatology Jul 2024
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents
PubMed: 38858603
DOI: 10.1038/s41584-024-01132-6