ORIGINAL RESEARCH Long-Term Efficacy of Tumor Necrosis Factor Inhibitors for the Treatment of Methotrexate-Naı ¨ve Rheumatoid Arthritis: Systematic Literature Review and Meta-Analysis La ´szlo ´ Gula ´csi . Zsombor Zrubka . Valentin Brodszky . Fanni Rencz . Rieke Alten . Zolta ´n Szekanecz . Ma ´rta Pe ´ntek Received: December 1, 2018 Ó Springer Healthcare Ltd., part of Springer Nature 2019 ABSTRACT 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 Con- trolled Trials were searched for randomized controlled trials (RCTs) involving treatment of methotrexate-naı ¨ve 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 La ´szlo ´ Gula ´csi and Zsombor Zrubka contributed equally to this work. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.7498988. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12325- 018-0869-8) contains supplementary material, which is available to authorized users. L. Gula ´csi (&) Á Z. Zrubka Á V. Brodszky Á F. Rencz Á M. Pe ´ntek Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary e-mail: laszlo.gulacsi@uni-corvinus.hu Z. Zrubka Doctoral School of Business and Management, Corvinus University of Budapest, Budapest, Hungary R. Alten Rheumatology Research Center, Schlosspark-Klinik Charite, University Medicine Berlin, Berlin, Germany Z. Szekanecz Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary M. Pe ´ntek Department of Rheumatology, Flo ´ r Ferenc County Hospital, Kistarcsa, Hungary Adv Ther https://doi.org/10.1007/s12325-018-0869-8