PMID- 28962590
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Sep 29
TI  - A somatization comorbidity phenotype impacts response to therapy in rheumatoid 
      arthritis: post-hoc results from the certolizumab pegol phase 4 PREDICT trial.
PG  - 215
LID - 10.1186/s13075-017-1412-z [doi]
LID - 215
AB  - BACKGROUND: Comorbidities may contribute to disease activity and treatment 
      response in rheumatoid arthritis (RA) patients. We defined a somatization 
      comorbidity phenotype (SCP) and examined its influence on response to 
      certolizumab pegol (CZP) using data from the PREDICT trial. METHODS: Patients in 
      PREDICT were randomized to the patient-reported Routine Assessment of Patient 
      Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) 
      for treatment response assessment. Post-hoc analyses identified patients with the 
      SCP, which included diagnosis of depression, fibromyalgia/myalgias, and/or use of 
      medications indicated for treatment of depression, anxiety, or neuropathic pain. 
      The effect of the SCP on RAPID3 or CDAI response at week 12 and low disease 
      activity (LDA; Disease Activity Score in 28 joints based on erythrocyte 
      sedimentation rate </= 3.2) at week 52, in week-12 responders, was analyzed using 
      non-parametric analysis of covariance (ANCOVA). RESULTS: At baseline, 43% 
      (313/733) of patients met the SCP classification. Patients with the SCP were 9% 
      more likely to withdraw from the trial. American College of Rheumatology 20% 
      (ACR20), ACR50, and ACR70 responses were 5-14% lower among those with the SCP, 
      and 11% more patients reported adverse events (AEs). Patients without SCP in the 
      CDAI arm were twice as likely to achieve LDA at week 52 compared with those with 
      SCP (32% versus 16%). No differentiation by SCP was observed in the RAPID3 arm 
      (pooled result 21.5%). CONCLUSIONS: We operationalized a potentially important 
      somatization comorbidity phenotype in a trial setting that was associated with a 
      substantially lower likelihood of treatment response and a higher frequency of 
      AEs. Including large numbers of patients with this phenotype in RA trials may 
      reduce the measured clinical effectiveness of a new molecule. TRIAL REGISTRATION: 
      ClinicalTrials.gov, NCT01255761 . Registered on 6 December 2010.
FAU - Curtis, Jeffrey R
AU  - Curtis JR
AD  - Division of Clinical Immunology and Rheumatology, University of Alabama at 
      Birmingham, FOT 802, 510 20th Street South, Birmingham, AL, 35294, USA. 
      jrcurtis@uabmc.edu.
FAU - Herrem, Christopher
AU  - Herrem C
AD  - Mylan, 1000 Mylan Blvd, Canonsburg, PA, 15317, USA.
FAU - Ndlovu, 'Matladi N
AU  - Ndlovu 'N
AD  - UCB Pharma, Allee de la Recherche 60, 1070, Brussels, Belgium.
FAU - O'Brien, Cathy
AU  - O'Brien C
AD  - UCB Pharma, Allee de la Recherche 60, 1070, Brussels, Belgium.
FAU - Yazici, Yusuf
AU  - Yazici Y
AD  - NYU Hospital for Joint Diseases, New York University School of Medicine, 301 East 
      17th Street, New York, NY, 10003, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01255761
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170929
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antirheumatic Agents)
RN  - UMD07X179E (Certolizumab Pegol)
SB  - IM
CIN - Arthritis Res Ther. 2019 Feb 20;21(1):65. PMID: 30786929
MH  - Adult
MH  - Aged
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/epidemiology
MH  - Certolizumab Pegol/*therapeutic use
MH  - Comorbidity
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Treatment Outcome
PMC - PMC5622491
OTO - NOTNLM
OT  - Anxiety
OT  - CDAI
OT  - Comorbidities
OT  - Depression
OT  - Disease activity
OT  - Fibromyalgia
OT  - Patient-reported outcomes
OT  - RAPID3
OT  - Rheumatoid arthritis
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study protocol, amendments, and 
      patient informed consent were reviewed by a national, regional, or Independent 
      Ethics Committee (IEC) or Institutional Review Board (IRB). Patient informed 
      consent was conducted in accordance with the current version of the applicable 
      regulatory and International Conference on Harmonization (ICH) Good Clinical 
      Practice (GCP) requirements, the ethical principles that have their origin in the 
      principles of the Declaration of Helsinki, and the local laws of the countries 
      involved. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: JRC: 
      research grants and consulting fees from UCB Pharma, Janssen, CORRONA, Amgen, 
      Pfizer, Bristol-Myers Squibb, Crescendo Bioscience. CH: Medical Director at 
      Mylan, former employee of UCB Pharma. MNN: employee of UCB Pharma. COB: employee 
      of UCB Pharma. YY: research grants from Bristol-Myers Squibb, Genentech, Celgene; 
      consulting fees from Bristol-Myers Squibb, Celgene, Samumed. PUBLISHER'S NOTE: 
      Springer Nature remains neutral with regard to jurisdictional claims in published 
      maps and institutional affiliations.
EDAT- 2017/10/01 06:00
MHDA- 2018/06/13 06:00
PMCR- 2017/09/29
CRDT- 2017/10/01 06:00
PHST- 2017/05/09 00:00 [received]
PHST- 2017/08/29 00:00 [accepted]
PHST- 2017/10/01 06:00 [entrez]
PHST- 2017/10/01 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
PHST- 2017/09/29 00:00 [pmc-release]
AID - 10.1186/s13075-017-1412-z [pii]
AID - 1412 [pii]
AID - 10.1186/s13075-017-1412-z [doi]
PST - epublish
SO  - Arthritis Res Ther. 2017 Sep 29;19(1):215. doi: 10.1186/s13075-017-1412-z.