PMID- 30886732
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20200420
IS  - 2056-5933 (Print)
IS  - 2056-5933 (Electronic)
IS  - 2056-5933 (Linking)
VI  - 5
IP  - 1
DP  - 2019
TI  - Treatment outcomes in patients with seropositive versus seronegative rheumatoid 
      arthritis in Phase III randomised clinical trials of tofacitinib.
PG  - e000742
LID - 10.1136/rmdopen-2018-000742 [doi]
LID - e000742
AB  - OBJECTIVES: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid 
      arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in 
      patients with seropositive vs seronegative RA. METHODS: Data were pooled from 
      five Phase III studies of conventional synthetic disease-modifying antirheumatic 
      drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step 
      [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync 
      [NCT00856544]; ORAL Standard [NCT00853385]). 'Serotype' subgroups were: 
      anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive 
      (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At 
      month 3, ACR20/50/70 response rates, Disease Activity Score 
      (DAS28-4[ESR])-defined remission (DAS28-4[ESR]<2.6) and low disease activity 
      (LDA; DAS28-4[ESR]</=3.2), changes from baseline (CFB) in Health Assessment 
      Questionnaire-Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36) 
      physical functioning and Functional Assessment of Chronic Illness Therapy-Fatigue 
      (FACIT-F) were evaluated. Safety endpoints were compared. RESULTS: Baseline 
      demographics/characteristics were similar across subgroups. Tofacitinib 
      significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB 
      in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than 
      anti-CCP-/RF- patients had ACR20/50/70 responses (ACR20/50: both tofacitinib 
      doses; ACR70: 10 mg two times a day). SF-36 physical functioning improved in 
      anti-CCP+/RF+, anti-CCP+/RF- and anti-CCP-/RF+ patients (both tofacitinib doses) 
      and anti-CCP-/RF- patients (10 mg two times a day) vs placebo. More anti-CCP+/RF+ 
      and anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(ESR) remission and 
      LDA with tofacitinib 10 mg two times a day. Frequency of adverse events (AEs), 
      serious AEs and discontinuations due to AEs were similar across subgroups. 
      CONCLUSION: Generally, tofacitinib efficacy (ACR20/50/70 responses) and safety 
      were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical 
      functioning appeared lower in anti-CCP- patients.
FAU - Bird, Paul
AU  - Bird P
AD  - University of New South Wales, Sydney, New South Wales, Australia.
FAU - Hall, Stephen
AU  - Hall S
AD  - Cabrini Health and Monash University, Melbourne, Victoria, Australia.
FAU - Nash, Peter
AU  - Nash P
AD  - University of Queensland, Brisbane, Queensland, Australia.
FAU - Connell, Carol A
AU  - Connell CA
AD  - Pfizer Inc, Groton, Connecticut, USA.
FAU - Kwok, Kenneth
AU  - Kwok K
AD  - Pfizer Inc, New York City, New York, USA.
FAU - Witcombe, David
AU  - Witcombe D
AD  - Pfizer Australia, Sydney, New South Wales, Australia.
FAU - Thirunavukkarasu, Krishan
AU  - Thirunavukkarasu K
AD  - Pfizer Australia, Sydney, New South Wales, Australia.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190223
PL  - England
TA  - RMD Open
JT  - RMD open
JID - 101662038
RN  - 0 (Anti-Citrullinated Protein Antibodies)
RN  - 0 (Biomarkers)
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
RN  - 9009-79-4 (Rheumatoid Factor)
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Citrullinated Protein Antibodies/blood/immunology
MH  - Arthritis, Rheumatoid/*blood/*drug therapy/immunology
MH  - *Biomarkers/blood
MH  - Female
MH  - Humans
MH  - Janus Kinase Inhibitors/pharmacology/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Patient Reported Outcome Measures
MH  - Piperidines/pharmacology/*therapeutic use
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Pyrimidines/pharmacology/*therapeutic use
MH  - Pyrroles/pharmacology/*therapeutic use
MH  - Rheumatoid Factor/blood
MH  - Risk Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC6397430
OTO - NOTNLM
OT  - anti-CCP
OT  - rheumatoid arthritis
OT  - rheumatoid factor
OT  - treatment
COIS- Competing interests: PB has participated in advisory boards and received 
      honoraria from AbbVie, BMS, Janssen, Pfizer Inc, Roche and UCB. SH has acted as a 
      consultant for AbbVie, Celgene, Eli Lilly, Janssen, Pfizer Inc and Roche. PN has 
      received funding for research and clinical trials, and honoraria for lectures and 
      advice, from Pfizer Inc. CAC and KK are employees of Pfizer Inc and hold 
      stock/stock options in Pfizer Inc. DW and KT are employees of Pfizer Australia 
      Pty. Ltd and hold stock/stock options in Pfizer Inc.
EDAT- 2019/03/20 06:00
MHDA- 2019/03/20 06:01
PMCR- 2019/02/23
CRDT- 2019/03/20 06:00
PHST- 2018/06/14 00:00 [received]
PHST- 2018/11/13 00:00 [revised]
PHST- 2018/12/03 00:00 [accepted]
PHST- 2019/03/20 06:00 [entrez]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2019/03/20 06:01 [medline]
PHST- 2019/02/23 00:00 [pmc-release]
AID - rmdopen-2018-000742 [pii]
AID - 10.1136/rmdopen-2018-000742 [doi]
PST - epublish
SO  - RMD Open. 2019 Feb 23;5(1):e000742. doi: 10.1136/rmdopen-2018-000742. eCollection 
      2019.