The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A Network Meta-Analysis

Abstract

ObjectivesTo evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice.MethodsWe searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment.Result72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors.ConclusionIn conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended.Systematic Review Registrationidentifier PROSPERO CRD42021276176.

Peripheral ulcerative keratitis, nodular episcleritis, and pulmonary nodules as the initial signs of rheumatic arthritis: A Case Report

“…Infliximab, a chimeric monoclonal antibody specific for the key proinflammatory cytokine tumor necrosis factor-alpha (TNFα), was reported effective and safe for the treatment of RA-related PUK ( 11 ). Currently, antitumors necrosis factor (anti-TNF) therapy has been proved as an efficacious therapeutic strategy in RA ( 12 , 13 ). Besides, PUK recurrence was observed after the discontinuation of infliximab.…”

Reversing the Inflammatory Process—25 Years of Tumor Necrosis Factor-α Inhibitors

“…Therapy with TNF-α inhibitors can reduce the risk of overall cardiovascular events, myocardial infarction, and serious venous thrombotic events (VTE) in RA patients [52]. The normalization of fibrinogen and thrombocytosis and the reduction of the expression of vascular endothelial growth factor, as well as of oxidative stress and endothelial dysfunction, by TNF-α inhibitors may reduce the relevant risk factors for atherosclerosis and cardiovascular events in patients with chronic inflammatory disease and increased cardiovascular risk, such as in RA [25,45,[52][53][54]. Patients with IBD are at increased risk of thrombotic events.…”

“…A recent network meta-analysis assessed the risk of malignancies (such as non-melanoma skin cancer and lymphoma), tuberculosis, and infections in RA patients with different TNF-α therapies. According to their findings, none of the 10 studied anti-TNF therapies resulted in an increased risk of serious infections, malignant tumors, and tuberculosis infection compared to placebo or conventional DMARDs therapy [53]. Further, RA patients with serious infections before the initiation of TNF-α inhibitor therapy were not at increased risk of subsequent serious infection and the hospitalization rate was comparable between patients continuously treated with the same TNF-α inhibitor and patients who switched to another TNF-α inhibitor, or even to a different mode of action [54].…”

Polymerized Network-Based Artificial Peroxisome Reprogramming Macrophages for Photoacoustic Imaging-Guided Treatment of Rheumatoid Arthritis

“…3,4 Though several biologics, such as tumor necrosis factor-α (TNF-α) inhibitors, have certain curative effects, 30−50% of patients still suffer poor efficacy or do not respond to the treatment. 5,6 Thus, it is essential to explore new therapeutic agents and strategies. 7,8 Inflammationassociated macrophages, including the proinflammatory M1 phenotype and the anti-inflammatory M2 phenotype, are closely associated with early inflammation and correlated with the severity of RA.…”

“…Rheumatoid arthritis (RA), a chronic systemic autoimmune inflammatory disease, has a high global prevalence of 0.5–1.0%. , Existing systematic medication has been subjected to low distribution in the inflamed joint area, poor bioavailability, and severe side effects. , Though several biologics, such as tumor necrosis factor-α (TNF-α) inhibitors, have certain curative effects, 30–50% of patients still suffer poor efficacy or do not respond to the treatment. , Thus, it is essential to explore new therapeutic agents and strategies. , Inflammation-associated macrophages, including the proinflammatory M1 phenotype and the anti-inflammatory M2 phenotype, are closely associated with early inflammation and correlated with the severity of RA. − M1 macrophages in inflamed synovial tissue can promote the expression of various proinflammatory factors, such as interleukin-1 (IL-1), TNF-α, IL-6, IL-18, and hypoxia inducible factor-1α (HIF-1α), which is also positively correlated with the generation of reactive oxygen species (ROS). − Thus, scavenging ROS, alleviating hypoxia, reducing neovascularization, and reprogramming macrophages can be an effective strategy for RA treatment. − …”