Introduction
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes persistent joint inflammation, leading to pain, stiffness, and eventual cartilage and bone destruction. The disease affects joints symmetrically and can cause deformities if untreated. Current treatments include NSAIDs, csDMARDs, tsDMARDs, bDMARDs, and glucocorticoids, with adalimumab (a bDMARD) and tofacitinib (a tsDMARD) being key options. Adalimumab, a fully humanized monoclonal antibody, inhibits TNF-α and reduces inflammation but may increase the risk of infections. Tofacitinib, an oral JAK inhibitor, offers effective monotherapy or combination therapy for RA but has been linked to dose-dependent risks like thrombosis and mortality, leading to FDA safety warnings for the JAK inhibitor class.
Although several trials have compared adalimumab and tofacitinib, clear evidence on their relative advantages remains limited. This study aims to systematically compare both drugs in terms of efficacy, disease control, safety, and quality of life. The goal is to guide clinicians in selecting an optimal, cost-effective therapy with rapid onset and strong therapeutic outcomes for RA patients.
Method
Literature search
This meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42024605000). A comprehensive search of PubMed, Embase, Web of Science, and Cochrane (till April 2025) identified studies comparing adalimumab and tofacitinib in rheumatoid arthritis. References were manually screened, and two authors independently selected eligible studies, resolving disagreements through discussion.
Inclusion and exclusion criteria
Included studies involved RA patients treated with tofacitinib (intervention) versus adalimumab (comparison), assessing outcomes like ACR20, VAS, DAS28-CRP, HAQ-DI, and adverse events. Eligible designs included RCTs and cohort studies. Excluded were non-original, single-arm, or incomplete data studies and reviews.
Data abstraction
Two authors independently extracted study details including design, population, interventions, outcomes, and adverse events. Discrepancies were resolved by a third author. Authors of original studies were contacted for missing data when needed.
Quality evaluation
RCTs were evaluated using the Cochrane RoB tool (seven domains), and cohort studies using the Newcastle-Ottawa Scale (scores ≥7 = high quality). Two authors assessed quality independently, resolving differences by discussion.
Statistical analysis
Review Manager 5.4.1 was used for data analysis. Standardized mean difference (SMD) and risk ratio (RR) were applied with 95% CIs under a random-effects model. Heterogeneity was tested using χ² and I² statistics, with I² >50% or P<0.1 indicating high heterogeneity. Sensitivity and subgroup analyses were conducted to assess robustness and identify heterogeneity sources.
Results
Literature retrieval, study characteristics, and baseline
Figure 1 illustrates the flowchart of literature retrieval and selection. A total of 2,360 studies from PubMed (n = 157), Embase (n = 1,530), Web of Science (n = 567), and Cochrane (n = 106) were identified through a systematic search.
Figure 1.Flowchart of the systematic search and selection process.
After screening 1,773 records, nine studies (14 comparison groups) involving 24,643 rheumatoid arthritis patients were included—six RCTs and three cohort studies. Meta-analysis showed that tofacitinib achieved a higher ACR20 response (RR = 1.28; P = 0.01) and greater improvements in VAS (SMD = 0.30; P = 0.03) and HAQ-DI (SMD = 0.20; P = 0.008) compared to adalimumab, though with substantial heterogeneity across outcomes. DAS28-CRP changes were similar between the two drugs (SMD = 0.02; P = 0.07).
Adverse event rates were comparable (RR = 0.96; P = 0.22) with low heterogeneity. Subgroup analysis revealed that higher doses of tofacitinib (>5 mg twice daily) produced better ACR20 responses, while lower doses showed no difference. Sensitivity analysis confirmed stable outcomes for ACR20, HAQ-DI, and adverse events, though variability persisted for VAS and DAS28-CRP, with the Fleischmann 2012e study contributing most to heterogeneity.
Discussion & Conclusion
Current RA treatments include NSAIDs, csDMARDs, tsDMARDs, bDMARDs, and glucocorticoids. TNF-α plays a key role in RA by promoting inflammation and bone damage, making it a major therapeutic target. Adalimumab blocks TNF-α, while tofacitinib inhibits JAK1 and JAK3 to reduce immune activation. This meta-analysis of nine studies found tofacitinib significantly better than adalimumab in improving ACR20, HAQ-DI, and VAS scores, with similar safety and DAS28-CRP outcomes. Higher doses of tofacitinib (>5 mg twice daily) showed stronger efficacy. However, long-term benefits and optimal dosing still need further study.
Tofacitinib improved pain and quality of life more effectively, though both drugs had comparable effects on reducing disease activity and bone damage. Adverse events were similar between groups, though some studies noted slightly higher risks early in tofacitinib use. Limitations include small sample sizes, regional bias, data insufficiency for key indicators like ACR50, and heterogeneity between study designs. Economic comparisons were also lacking. Despite these, the analysis provides updated evidence supporting tofacitinib as a faster-acting and effective option for RA. Future large-scale, multicenter trials are needed to validate its long-term safety, efficacy, and cost-effectiveness.
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