PMID- 27217051
OWN - NLM
STAT- MEDLINE
DCOM- 20180521
LR  - 20220330
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Linking)
VI  - 17
IP  - 5
DP  - 2017 Oct
TI  - Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse 
      events in rheumatoid arthritis.
PG  - 412-418
LID - 10.1038/tpj.2016.36 [doi]
AB  - We describe a novel approach to investigate and evaluate combined effect of a 
      large number of clinical and pharmacogenetic factors on treatment outcome. We 
      have used this approach to investigate predictors of methotrexate (MTX)-induced 
      adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis 
      (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in 
      MTX transporters, folate and adenosine pathways. The effect of clinical and 
      pharmacogenetic factors was assessed with penalized regression in the 
      cause-specific Cox proportional hazards model. The predictive capacity was 
      evaluated with the area under time-dependent receiver operating characteristic 
      curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were 
      associated with discontinuation because of AEs in clinical-pharmacogenetic model. 
      Cross-validation showed that both clinical-pharmacogenetic model and nongenetic 
      model had worthless predictive ability for MTX discontinuation because of AEs. 
      These models could be further improved, either with additional polymorphisms or 
      with epigenetic predictors.
FAU - Jenko, B
AU  - Jenko B
AD  - Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, 
      University of Ljubljana, Ljubljana, Slovenia.
FAU - Lusa, L
AU  - Lusa L
AD  - Faculty of Medicine, Institute for Biostatistics and Medical Informatics, 
      University of Ljubljana, Ljubljana, Slovenia.
FAU - Tomsic, M
AU  - Tomsic M
AD  - Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, 
      Slovenia.
AD  - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
FAU - Praprotnik, S
AU  - Praprotnik S
AD  - Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, 
      Slovenia.
AD  - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
FAU - Dolzan, V
AU  - Dolzan V
AD  - Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, 
      University of Ljubljana, Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
DEP - 20160524
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nucleoside Transport Proteins)
RN  - 0 (Reduced Folate Carrier Protein)
RN  - 0 (SLC19A1 protein, human)
RN  - 0 (adenosine transporter)
RN  - EC 2.1.1.45 (TYMS protein, human)
RN  - EC 2.1.1.45 (Thymidylate Synthase)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
MH  - Aged
MH  - Antirheumatic Agents/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Methotrexate/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Middle Aged
MH  - Neoplasm Proteins/genetics
MH  - Nucleoside Transport Proteins/genetics
MH  - Pharmacogenomic Testing
MH  - *Polymorphism, Genetic
MH  - Predictive Value of Tests
MH  - Proportional Hazards Models
MH  - Reduced Folate Carrier Protein/genetics
MH  - Thymidylate Synthase/genetics
MH  - Treatment Outcome
EDAT- 2016/05/25 06:00
MHDA- 2018/05/22 06:00
CRDT- 2016/05/25 06:00
PHST- 2015/11/03 00:00 [received]
PHST- 2016/02/04 00:00 [revised]
PHST- 2016/04/15 00:00 [accepted]
PHST- 2016/05/25 06:00 [pubmed]
PHST- 2018/05/22 06:00 [medline]
PHST- 2016/05/25 06:00 [entrez]
AID - tpj201636 [pii]
AID - 10.1038/tpj.2016.36 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2017 Oct;17(5):412-418. doi: 10.1038/tpj.2016.36. Epub 2016 
      May 24.