Long-Term Efficacy of Tumor Necrosis Factor Inhibitors for the Treatment of Methotrexate-Naïve Rheumatoid Arthritis: Systematic Literature Review and Meta-Analysis

László Gulácsi, Zsombor Zrubka, Valentin Brodszky, Fanni Rencz, Rieke Alten, Zoltán Szekanecz, Márta Péntek

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Introduction: Synthesis of evidence on the long-term use of first-line biologic therapy in patients with early rheumatoid arthritis (RA) is required. We compared the efficacy of up to 5 years’ treatment with first-line tumor necrosis factor inhibitors (TNFis) versus other treatment strategies in this population. Methods: Previous systematic reviews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) involving treatment of methotrexate-naïve RA patients with first-line TNFis. Literature was synthesized qualitatively, and a meta-analysis conducted to evaluate American College of Rheumatology (ACR) responses, clinical remission defined by any standard measure, and Health Assessment Questionnaire Disability Index (HAQ) at Years 2 and/or 5. Results: Ten RCTs involving 4306 patients [first-line TNFi, n = 2234; other treatment strategies (control), n = 2072] were included in the meta-analysis. Three studies were double-blind for the first 2 years, while seven were partly/completely open label during this period. Five studies reported data at Year 5; all were open label at this time point. At Year 2, ACR50 response, ACR70 response and remission rates were significantly improved with first-line TNFi versus control in double-blind RCTs [log-odds ratio (OR) 0.32 [95% confidence interval (CI) 0.02, 0.62; p = 0.035], log-OR 0.48 (95% CI 0.20, 0.77; p = 0.001), and log-OR 0.44 (95% CI 0.13, 0.74; p = 0.005), respectively], but not in open-label studies. No significant between-group differences were observed in mean HAQ at Year 2 in double-blind or open-label RCTs or in ACR response or remission outcomes at Year 5. Conclusion: In double-blind studies, 2-year efficacy outcomes were significantly improved with first-line TNFi versus other treatment strategies in patients with MTX-naïve RA. No significant differences in these outcomes were observed when data from open-label RCTs were considered on their own. Further data on the efficacy of TNFi therapy over ≥ 2 years in patients with methotrexate-naïve RA are required. Plain Language Summary: Plain language summary available for this article.

Original languageEnglish
Pages (from-to)721-745
Number of pages25
JournalAdvances in Therapy
Issue number3
Publication statusPublished - Mar 1 2019



  • Biologic
  • Disease-modifying antirheumatic drug
  • Early
  • Efficacy
  • First line
  • Meta-analysis
  • Methotrexate-naïve
  • Systematic review
  • Tumor necrosis factor inhibitor

ASJC Scopus subject areas

  • Pharmacology (medical)

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