Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial
The LancetPublished 16 June 2017
Roy Fleischmann, Eduardo Mysler, Stephen Hall, Alan Kivitz, Robert J. Moots, Zhen Luo
Citations471
SJR quartileQ1
SJR score12.11
SNIP22.72
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TL;DR
Tofacitinib monotherapy was not shown to be non-inferior to either combination of adalimumab and methotrexate, and no new or unexpected safety issues were reported for either treatment in this study for up to 1 year.
Abstract
Pfizer Inc.
Keywords
Medicine
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