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Gene-body mass index interactions are associated with methotrexate toxicity in rheumatoid arthritis
  1. Stella Aslibekyan1,
  2. Jin Sha1,
  3. David T Redden2,
  4. Larry W Moreland3,
  5. James R O'Dell4,
  6. Jeffrey R Curtis5,
  7. Ted R Mikuls4,
  8. Richard J Reynolds1,
  9. Maria I Danila5,
  10. S Louis Bridges Jr5
  1. 1 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA
  3. 3 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittburgh, Pennsylvania, USA
  4. 4 University of Nebraska Medical Center, Omaha, Nebraska, USA
  5. 5 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  1. Correspondence to Dr Stella Aslibekyan, Departments of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, RPHB 230J, Birmingham, AL 35294, USA; saslibek{at}uab.edu

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Despite the introduction of multiple biological agents for the treatment of rheumatoid arthritis (RA), methotrexate (MTX) remains the initial drug of choice.1 Response to MTX therapy is highly heterogeneous between individuals. An extensive body of work illustrates the complexity of MTX response architecture, which includes genetic polymorphisms, environmental factors and gene-gene interactions.2 Among environmental contributors, elevated body mass index (BMI) has emerged as an important predictor of MTX toxicity.3 Using data from the Treatment of Aggressive Rheumatoid Arthritis (TEAR) trial,4 we present first evidence linking the risk of MTX-associated toxicity to interactions between genotype and BMI.

The TEAR trial, described in previous publications,4 compared two strategies (early intensive …

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Footnotes

  • Contributors SA designed the study and wrote the manuscript; JS and DTR conducted the statistical analyses; LWM, JRO, JRC and SLB conducted the parent TEAR trial and contributed to the interpretation of the findings; TRM measured smoking status of TEAR participants; DKA interpreted the findings and revised the draft paper.

  • Funding This analysis was funded by the National Institutes of Health (NIH P60 AR048095 and ARRA supplement 3P60AR048095-07S1; NIH R01 AR052658; 5UL1RR025777-03, 5KL2RR025776-03, 5TL1RR025775-03), while the parent TEAR trial was funded by Amgen.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Institutional Review Board at the University of Alabama-Birmingham.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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