Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis

Abstract

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient’s response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases.Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX).Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81–0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79–0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05–1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68–1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding.Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Forty-Eight-Month Monitoring of Disease Activity in Patients with Long-Standing Rheumatoid Arthritis Treated with TNF-α Inhibitors: Time for Clinical Outcome Prediction and Biosimilar vs Biologic Originator Performance

“…Currently, there is still a lack of information about the real-world effectiveness of TNF-α inhibitors, notwithstanding their ability to slow RA progression recorded in several randomized clinical trials [ 22 ]. Indeed, few results produced from these studies revealed that adalimumab and etanercept may be effective treatment options for patients with an inadequate response to infliximab, but they reflect a small sample size of patients that limits generalizability to real-world subjects [ 22 , 23 ]. Noteworthy, adalimumab and etanercept biosimilars demonstrated comparable efficacy to the corresponding original biologics in real-life cohorts of patients with RA [ 24 , 25 ].…”

The Role of Etanercept in Controlling Clinical and Radiological Progression in Rheumatoid Arthritis: A Systematic Review

“…Etanercept (ETN) is a soluble TNF receptor fusion protein that binds to and deactivates TNF, thus reducing joint inflammation [16][17][18][19][20][21][22]. It is prescribed when one or more cDMARDs fail to control the clinical symptoms of RA [16][17][18][19][20][21][22].…”

“…Etanercept (ETN) is a soluble TNF receptor fusion protein that binds to and deactivates TNF, thus reducing joint inflammation [16][17][18][19][20][21][22]. It is prescribed when one or more cDMARDs fail to control the clinical symptoms of RA [16][17][18][19][20][21][22]. Various systematic reviews and meta-analyses have been done in the past to check the efficacy and safety of ETN in patients with RA.…”

Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis

“… 2–4 Targeted therapy strategies have improved outcomes for many patients with reduced swollen joint counts (SJCs) and measures of inflammation such as the erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and have achieved a major goal of reducing progressive joint damage. 5 6 Unfortunately, it is now clear from multiple studies that patient global assessments, tender joint counts (TJCs) and pain scores remain high even as levels of inflammation and synovitis have reduced. 7 8 …”

“…The specific objective of this study is to accurately characterise the causes of pain in patients with RA with moderate and high disease activity (defined by DAS28(ESR)), as these patients had not achieved widely agreed goals of therapy for RA and will be considered for increased therapy. 5 6 We collected detailed clinical features, serological markers and PROMS, together with a comprehensive ultrasound (US) examination of 44 joints. It is then possible to group patients with active inflammatory joint disease detected by comprehensive US power doppler (PD) assessment and associated variables into those with possible (secondary) FM.…”