PMID- 27723271
OWN - NLM
STAT- MEDLINE
DCOM- 20170712
LR  - 20220317
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 69
IP  - 3
DP  - 2017 Mar
TI  - Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis 
      and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment.
PG  - 506-517
LID - 10.1002/art.39953 [doi]
AB  - OBJECTIVE: We undertook this phase III study to evaluate baricitinib, an orally 
      administered JAK-1/JAK-2 inhibitor, as monotherapy or combined with methotrexate 
      (MTX) compared to MTX monotherapy in patients with active rheumatoid arthritis 
      (RA) who had received no or minimal conventional synthetic disease-modifying 
      antirheumatic drugs (DMARDs) and who were naive to biologic DMARDs. METHODS: A 
      total of 588 patients were randomized 4:3:4 to receive MTX monotherapy (once 
      weekly), baricitinib monotherapy (4 mg once daily), or the combination of 
      baricitinib and MTX for 52 weeks. The primary end point assessment was a 
      noninferiority comparison of baricitinib monotherapy to MTX monotherapy based on 
      the proportion of patients meeting the American College of Rheumatology 20% 
      improvement criteria (achieving an ACR20 response) at week 24. RESULTS: The study 
      met its primary objective. Moreover, baricitinib monotherapy was found to be 
      superior to MTX monotherapy at week 24, with a higher ACR20 response rate (77% 
      versus 62%; P </= 0.01). Similar results were observed for combination therapy. 
      Compared to MTX monotherapy, significant improvements in disease activity and 
      physical function were observed for both baricitinib groups as early as week 1. 
      Radiographic progression was reduced in both baricitinib groups compared to MTX 
      monotherapy; the difference was statistically significant for baricitinib plus 
      MTX. The rates of serious adverse events (AEs) were similar across treatment 
      groups, while rates of some treatment-emergent AEs, including infections, were 
      increased with baricitinib plus MTX. Three deaths were reported, all occurring in 
      the MTX monotherapy group. Malignancies, including nonmelanoma skin cancer, were 
      reported in 1 patient receiving MTX monotherapy, 1 receiving baricitinib 
      monotherapy, and 4 receiving baricitinib plus MTX. CONCLUSION: Baricitinib alone 
      or in combination with MTX demonstrated superior efficacy with acceptable safety 
      compared to MTX monotherapy as initial therapy for patients with active RA.
CI  - (c) 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. 
      on behalf of the American College of Rheumatology.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Metroplex Clinical Research Center, Dallas, Texas.
FAU - Schiff, Michael
AU  - Schiff M
AD  - University of Colorado, Denver.
FAU - van der Heijde, Desiree
AU  - van der Heijde D
AD  - Leiden University Medical Center, Leiden, The Netherlands, and Imaging 
      Rheumatology BV, Meerssen, The Netherlands.
FAU - Ramos-Remus, Cesar
AU  - Ramos-Remus C
AD  - Unidad de Investigacion en Enfermedades Cronico-Degenerativas, Guadalajara, 
      Mexico.
FAU - Spindler, Alberto
AU  - Spindler A
AD  - Centro Medico Privado de Reumatologia, Tucuman, Argentina.
FAU - Stanislav, Marina
AU  - Stanislav M
AD  - Scientific Research Institute of Rheumatology, Russian Academy of Medical 
      Sciences, Moscow, Russia.
FAU - Zerbini, Cristiano A F
AU  - Zerbini CA
AD  - Centro Paulista de Investigacao Clinica, Sao Paulo, Brazil.
FAU - Gurbuz, Sirel
AU  - Gurbuz S
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Dickson, Christina
AU  - Dickson C
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - de Bono, Stephanie
AU  - de Bono S
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Schlichting, Douglas
AU  - Schlichting D
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Beattie, Scott
AU  - Beattie S
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Kuo, Wen-Ling
AU  - Kuo WL
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Rooney, Terence
AU  - Rooney T
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Macias, William
AU  - Macias W
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Takeuchi, Tsutomu
AU  - Takeuchi T
AD  - Keio University School of Medicine, Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01711359
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Azetidines)
RN  - 0 (Purines)
RN  - 0 (Pyrazoles)
RN  - 0 (Sulfonamides)
RN  - ISP4442I3Y (baricitinib)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Azetidines/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Male
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - Purines
MH  - Pyrazoles
MH  - Sulfonamides/*therapeutic use
PMC - PMC5347954
EDAT- 2016/10/11 06:00
MHDA- 2017/07/14 06:00
PMCR- 2017/03/13
CRDT- 2016/10/11 06:00
PHST- 2016/05/27 00:00 [received]
PHST- 2016/10/05 00:00 [accepted]
PHST- 2016/10/11 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/10/11 06:00 [entrez]
PHST- 2017/03/13 00:00 [pmc-release]
AID - ART39953 [pii]
AID - 10.1002/art.39953 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2017 Mar;69(3):506-517. doi: 10.1002/art.39953.