PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
infliximab

Overview

Generic Names: Ig gamma-1 chain C region
Trade Names: Remicade (Centocor Inc)
PharmGKB Accession Id: PA452639

Description

Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion (source: Drug Bank)

Indication

For treatment of Crohn's disease, psoriasis, rheumatoid arthitis and ankylosing spondylitis (source: Drug Bank)

ATC Therapeutic Category

  • L04AA:Selective immunosuppressants

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa (source: Drug Bank)

Pharmacology

Used in the treatment of auto-immune disorders such as Crohn's disease and rheumatoid arthritis. Infliximab binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1061622 at chr1:12175542 in TNFRSF1B
    For this SNP in the TNFRSF1B gene a significant correlation was found between 196R allele carriers and low response to infliximab therapy.
    Variant Name:
    TNFRSF1B: M196R
    Related Drugs:
    infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18565259
  2. rs983332 at chr1:87904968
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000005; OR: 10.2 (2.6, 59.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  3. rs928655 at chr1:89622162 in GBP6
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.00003; OR: 5.5 (1.8, 20.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  4. rs396991 at chr1:159781166 in FCGR3A
    This variant may be a useful marker to predict response to infliximab in Japanese patients with rheumatoid arthritis.
    Variant Name:
    FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
    Related Drugs:
    infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:19005160
  5. rs13393173 at chr2:169097337 in LASS6
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 6.8 (1.7, 40.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  6. rs437943 at chr4:35048493
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  7. rs1800629 at chr6:31651010 in LTA, TNF
    The TNF:(-308)G>A polymorphism is a weak marker for response to anti-TNF treatment, with A-allele carriers being significantly less likely to respond than patients with the GG genotype.
    Variant Name:
    TNF:(-308)G>A; -308G>A
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:17638513
  8. rs10945919 at chr6:164106667
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000003; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  9. rs854547 at chr7:94761792 in PPP1R9A
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000006; OR: 3.6 (1.5, 9.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  10. rs854548 at chr7:94763756 in PON1, PPP1R9A
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 8.5 (2.6, 36.5)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  11. rs854555 at chr7:94768327 in PON1
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  12. rs868856 at chr9:27479251 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  13. rs7046653 at chr9:27480967 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  14. rs2814707 at chr9:27526397 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 5.2 (1.8, 16.7)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  15. rs3849942 at chr9:27533281
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000005; OR: 5.0 (1.7, 15.8)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  16. rs774359 at chr9:27551049 in C9orf72
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000006; OR: 5.4 (1.9, 17.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  17. rs6138150 at chr20:23795009
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 11.1 (2.5, 103.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  18. rs6028945 at chr20:38254219
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000002; OR: 11.2 (2.3, 108.1)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  19. rs6071980 at chr20:38301990
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 7.6 (1.9, 44.6)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
ADORA1
  • CO
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA2A
  • CO
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA2B
  • CO
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA3
  • CO
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data No literature annotations Not annotated
C9orf72
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
CARD15
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CRP
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
FCGR3A
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data No literature annotations Not annotated
GBP6
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data No literature annotations Not annotated
LASS6
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
LTA
  •   
  • PD
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
MOBKL2B
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
PON1
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data No literature annotations Not annotated
PPP1R9A
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNF
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNFRSF1A
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNFRSF1B
  •   
  • PD
  •   
  •   
  • GN
Publications, Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
LTB Uncurated Annotation (source: Drug Bank)
TNF Uncurated Annotation (source: Drug Bank)
TNFRSF1B Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Arthritis, Rheumatoid
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Crohn Disease
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Inflammatory Bowel Diseases
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Lupus erythematosus
  • CO
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00065

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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