Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial
Annals of the Rheumatic DiseasesPublished 29 October 2015Open access
Gerd R Burmester, William F. C. Rigby, Ronald van Vollenhoven, Jonathan Kay, Andrea Rubbert‐Roth, Ariella Kelman
Citations192
SJR quartileQ1
SJR score5.73
SNIP4.44
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TL;DR
TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA and demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints.
Abstract
ClinicalTrials.gov, number NCT01007435.
Keywords
Medicine
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